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] | {"Title": "Severe volcanic SO 2 exposure and respiratory morbidities in the Icelandic population \u2013 a register study", "Authors": "Carlsen Hanne Krage, Valdimarsd\u00f3ttir Unnur, Briem Haraldur, Dominici Francesca, Finnbjornsdottir Ragnhildur Gudrun, J\u00f3hannsson Thorsteinn, Aspelund Thor, Gislason Thorarinn, Gudnason Thorolfur", "Abstract": "Abstract Background The Holuhraun volcanic eruption September 2014 to February 2015 emitted large amounts of sulfur dioxide (SO 2 ). Objectives The aim of this study was to determine the association between volcanic SO 2 gases on general population respiratory health in the Icelandic capital area some 250 km from the eruption site. Methods Respiratory health outcomes were: asthma medication dispensing (AMD) from the Icelandic Medicines Register, medical doctor consultations in primary care (PCMD) and hospital emergency department visits (HED) in Reykjav\u00edk (population: 215 000) for respiratory disease from 1 January 2010 to 31 December 2014. The associations between daily counts of health events,and daily mean SO2 concentration and high SO2 levels (24-hour mean SO2>125\u00b5g/m3) were analyzed using generalized additive models. Results After the eruption began, AMD was higher than before (129.4 vs . 158.4 individuals per day, p <0.05). Increases in SO 2 concentration were associated with an estimated increase in AMD by 1.05% (95% CI 0.48 - 1.62%) per 10 \u00b5g/m 3 at lag 0-2, 1.51% (95% CI 0.63 \u2013 2.40%) increase in individuals under 18 years of age. PCMD for respiratory causes increased by 1.52% (95% CI 1.04 -2.00%) per 10 \u00b5g/m 3 SO 2 at lag 0-2. For HED, only effect estimated for individuals aged 64 years and older were significantly increased, by 1.541% (95% CI 0.02-3.07%) per 10 \u00b5g/m 3 SO 2 at lag 0-2. Following days with SO 2 levels above 125 \u00b5g/m 3 , AMD and PCMD were increased in all age groups, in AMD mostly so in individuals under 18 by 20.4%(95%CI 4.8 \u2013 23.4%), and adult PCMD visits by 24.1%(95%CI 16.8 \u2013 31.3%). HED was significantly increased in elderly by 26.3% (95%CI 5.56-47.0). Discussion High levels of volcanic SO 2 are associated with increases in dispensing of AMD, and health care utilization in primary and tertiary care. Individuals with prevalent respiratory disease may be particularly susceptible. Funding The study was funded by the Icelandic Ministry of Health.", "URL": "https://doi.org/10.1101/19013474"} |
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] | {"Title": "The Pan-Cancer Landscape of Prognostic Germline Variants in 10,582 Patients", "Authors": "Chatrath Ajay, Przanowska Roza, Kiran Shashi, Su Zhangli, Saha Shekhar, Wilson Briana, Tsunematsu Takaaki, Ahn Ji-Hye, Lee Kyung Yong, Paulsen Teressa, Sobierajska Ewelina, Kiran Manjari, Tang Xiwei, Li Tianxi, Kumar Pankaj, Ratan Aakrosh, Dutta Anindya", "Abstract": "Abstract While clinical data provides physicians with information about patient prognosis, genomic data can further improve these predictions. We analyzed sequencing data from over 10,000 cancer patients and identified hundreds of prognostic germline variants using multivariate Cox regression models. These variants provide information about patient outcomes beyond clinical information currently in use and may augment clinical decisions based on expected tumor aggressiveness. Molecularly, at least twelve of the germline variants are likely associated with patient outcome through perturbation of protein structure and at least five through association with gene expression differences. About half of these germline variants are in previously reported tumor suppressors or oncogenes, with the other half pointing to loci of previously unstudied genes in the literature that should be further investigated for roles in cancers. Our results suggest that germline variation contributes to tumor progression across most cancers and contains patient outcome information not captured by clinical factors.", "URL": "https://doi.org/10.1101/19010264"} |
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] | {"Title": "Identifying Ashkenazi Jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry", "Authors": "Tennen Ruth I., Laskey Sarah B., Koelsch Bertram L., McIntyre Matthew H., Tung Joyce Y.", "Abstract": "ABSTRACT Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants \u2014 185delAG (c.68_69delAG), 5382insC (c.5266dupC), and 6174delT (c.5946delT) \u2014 are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically used to recommend individuals for BRCA testing: self-reported Jewish ancestry and family history of breast, ovarian, prostate, or pancreatic cancer. Of the 1,967 carriers who provided self-reported ancestry information, 21% did not self-report any Jewish ancestry; of these individuals, more than half (62%) do have detectable Ashkenazi Jewish genetic ancestry. In addition, of the 343 carriers who provided both ancestry and family history information, 44% did not have a first-degree family history of a BRCA -related cancer and, in the absence of a personal history of cancer, would therefore be unlikely to qualify for clinical genetic testing. These findings provide support for the growing call for broader access to BRCA genetic testing.", "URL": "https://doi.org/10.1101/19001032"} |
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] | {"Title": "Time to death and its Predictors among Adult TB/HIV Co-Infected Patients in Mizan Tepi University Teaching Hospital, South West Ethiopia", "Authors": "Wondimu Wondimagegn, Dube Lamessa, Kabeta Teshome", "Abstract": "Abstract Background Tuberculosis (TB) and Human Immuno Deficiency Virus (HIV) co-infection represents a complex pathogenic scenario with synergistic effect and leads to about 300,000 HIV-associated TB deaths in the world in 2017. Despite this burden of death, time to death and its predictors among TB-HIV co-infected patient was not adequately studied; and the existing evidences are inconsistent. Therefore, this study was aimed to determine time to death and identify its predictors among adult TB/HIV co-infected patients. Method Retrospective cohort study was conducted by reviewing registers of randomly selected 364 TB/HIV co-infected patients enrolled in health care from July 2, 2007 up to July 1, 2017 at Mizan Tepi University Teaching Hospital. The hospital was located in Bench Maji Zone, South West Ethiopia. Data were collected from March 1 through 31, 2018, entered to Epi data 3.1 and exported to SPSS version 21. Each patient was followed from date of TB treatment initiation till death, loss to follow up and treatment completed. On the other hand, events other than death were considered as censored. After checking the proportional hazard model assumption, Cox-regression was used to identify the predictors. In bivariable analyses, P-value\u22640.25 was used to identify candidate variables for multivariable analysis. The 95% CI of hazard ratio (HR) with respective P-value <0.05 was used to declare significance in the final model. Result All the 364 patients were followed for 1,654 person months. There were 83 (22.8%) deaths and most 38 (45.8%) were occurring within the first two months of anti-TB treatment initiation. The overall incidence rate and median survival time were 5.02 per 100 person months (95% CI: 4.05, 6.22) and 10 months respectively. Statistically significant better survival was observed among patients: with CD4 \u2265 200 cells/mm 3 (P<0.001), who had a history of cotrimoxazole preventive therapy (CPT) use (P<0.001), who disclose their HIV status (P<0.001) and with working functional status (P<0.001). Not using CPT (adjusted hazard ratio [AHR] =1.72; P=0.023), bedridden functional status (AHR=2.55; P=0.007), not disclosing HIV status (AHR=4.03; P<0.001) and CD4 < 200 cells/mm 3 (AHR=6.05; P<0.001) were predictors of time to death among TB/HIV co-infected patients. Conclusion The median survival time was 10 months and poor survival was associated with low CD4 count, not using CPT, not disclosing HIV status and having bedridden functional status. Close monitoring of bedridden and low CD4 count patients, prompt CPT initiation and encouraging HIV status disclosure are recommended.", "URL": "https://doi.org/10.1101/19004234"} |
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] | {"Title": "Planning sEEG implantation using automated lesion detection: retrospective feasibility study", "Authors": "Wagstyl Konrad, Adler Sophie, Pimpel Birgit, Chari Aswin, Seunarine Kiran, Lorio Sara, Thornton Rachel, Baldeweg Torsten, Tisdall Martin", "Abstract": "Abstract Objective A retrospective, cross-sectional study to evaluate the feasibility and potential benefits of incorporating deep-learning on structural MRI into planning stereoelectroencephalography (sEEG) implantation in paediatric patients with diagnostically complex drug-resistant epilepsy. This study aims to assess the degree of co-localisation between automated lesion detection and the seizure onset zone (SOZ) as assessed by sEEG. Methods A neural network classifier was applied to cortical features from MRI data from three cohorts. 1) The network was trained and cross-validated using 34 patients with visible focal cortical dysplasias (FCDs). 2) Specificity was assessed in 20 paediatric healthy controls. 3) Feasibility for incorporation into sEEG implantation plans was evaluated in 38 sEEG patients. Coordinates of sEEG contacts were coregistered with classifier-predicted lesions. sEEG contacts in seizure onset and irritative tissue were identified by clinical neurophysiologists. A distance of <10mm between SOZ contacts and classifier-predicted lesions was considered co-localisation. Results In patients with radiologically-defined lesions, classifier sensitivity was 74% (25/34 lesions detected). No clusters were detected in the controls (specificity 100%). Of 34 sEEG patients, 21 patients had a focal cortical SOZ. Of these there was co-localisation between classifier output and SOZ contacts in 62%. The algorithm detected 7/8 histopathologically-confirmed FCDs (86%). Conclusions There was a high degree of co-localisation between automated lesion detection and sEEG. We have created a framework for incorporation of deep-learning based MRI lesion detection into sEEG implantation planning. Our findings demonstrate that automated MRI analysis could be used to plan optimal electrode trajectories.", "URL": "https://doi.org/10.1101/2019.12.08.19013979"} |
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] | {"Title": "Opioid Overdose in Ohio: Comprehensive Analysis of Associated Socioeconomic Factors", "Authors": "Park Chihyun, Crawford Sara, Lopez Rocio, Seballos Anna, Clemenceau Jean R., Coy Tyler, Atluri Gowtham, Hwang Tae Hyun", "Abstract": "ABSTRACT Objective Our study focused on identifying socioeconomic factors associated with death by opioid overdose in Ohio communities at the census tract level. Materials and Methods A large-scale vital statistic dataset from Ohio Department of Health (ODH) and U.S. Census datasets were used to obtain opioid-related death rate and socioeconomic characteristics for all census tracts in Ohio. Regression analysis was performed to identify the relationships between socioeconomic factors of census tracts and the opioid-related death rate for both urban and rural tracts. Results In Ohio from 2010-2016, whites, males, and people aged 25-44 had the highest opioid-related death rates. At the census tract level, higher death rates were associated with certain socioeconomic characteristics (e.g. percentage of the census tract population living in urban areas, percentage divorced/separated, percentage of vacant housing units). Predominately rural areas had a different population composition than urban areas, and death rates in rural areas exhibited fewer associations with socioeconomic characteristics. Discussion Predictive models of opioid-related death rates based on census tract-level characteristics held for urban areas more than rural ones, reflecting the recently observed rural-to-urban geographic shift in opioid-related deaths. Future research is needed to examine the geographic distribution of opioid abuse throughout Ohio and in other states. Conclusion Regression analysis identified associations between population characteristics and opioid-related death rates of Ohio census tracts. These analyses can help government officials and law official workers prevent, predict and combat opioid abuse at the community level.", "URL": "https://doi.org/10.1101/19005140"} |
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] | {"Title": "Using compartmental models to simulate directed acyclic graphs to explore competing causal mechanisms underlying epidemiological study data", "Authors": "Havumaki Joshua, Eisenberg Marisa C.", "Abstract": "1 Abstract Accurately estimating the effect of an exposure on an outcome requires understanding how variables relevant to a study question are causally related to each other. Directed acyclic graphs (DAGs) are used in epidemiology to understand causal processes and determine appropriate statistical approaches to obtain unbiased measures of effect. Compartmental models (CMs) are also used to represent different causal mechanisms, by depicting flows between disease states on the population level. In this paper, we extend a mapping between DAGs and CMs to show how DAG\u2013derived CMs can be used to compare competing causal mechanisms by simulating epidemiological studies and conducting statistical analyses on the simulated data. Through this framework, we can evaluate how robust simulated epidemiological study results are to different biases in study design and underlying causal mechanisms. As a case study, we simulated a longitudinal cohort study to examine the obesity paradox: the apparent protective effect of obesity on mortality among diabetic ever-smokers, but not among diabetic never-smokers. Our simulations illustrate how study design bias (e.g., reverse causation), can lead to the obesity paradox. Ultimately, we show the utility of transforming DAGs into in silico laboratories within which researchers can systematically evaluate bias, and inform analyses and study design.", "URL": "https://doi.org/10.1101/19007922"} |
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] | {"Title": "Patterns of Autism Symptoms: Hidden Structure in the ADOS and ADI-R instruments", "Authors": "Lefort-Besnard J\u00e9r\u00e9my, Vogeley Kai, Schilbach Leonhard, Varoquaux Ga\u00ebl, Thirion Bertrand, Dumas Guillaume, Bzdok Danilo", "Abstract": "ABSTRACT We simultaneously revisited the ADI-R and ADOS with a comprehensive data-analytics strategy. Here, the combination of pattern analysis algorithms and an extensive data resources (n=266 patients aged 7 to 49 years) allowed identifying coherent clinical constellations in and across ADI-R and ADOS assessments widespread in clinical practice. The collective results of the clustering and sparse regression approaches suggest that identifying autism subtypes and severity for a given individual may be most manifested in the social and communication domains of the ADI-R. Additionally, our quantitative investigation revealed that disease-specific patterns of ADI-R and ADOS scores can be uncovered when studying sex, age or level of FIQ in patients.", "URL": "https://doi.org/10.1101/19007419"} |
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] | {"Title": "Increased Frequency of Acute Illness and Hospitalizations in Infants and Toddlers with Congenital Adrenal Hyperplasia", "Authors": "Tseng Teresa, Seagroves Amy, Koppin Christina M., Keenan Madison, Putterman Elana, Nguyen Eugene, Chand Sanjay, Geffner Mitchell E., Chang Todd P., Kim Mimi S.", "Abstract": "Abstract Purpose Infants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for adrenal crisis and associated sequelae. To better understand acute illness at this early age, we determined the frequency and severity of acute illness and hospitalizations between 0-4 years of age, both within CAH and compared to controls. We also evaluated the impact of pre-hospital stress-dose hydrocortisone on Emergency Department (ED) visits and hospitalizations. Methods We performed a retrospective study of 40 CAH youth and 27 age-matched controls at a tertiary center. Characteristics of acute illnesses during the first 4 years of life were recorded, including fever, vomiting, diarrhea, ED visits, hospitalizations, abnormal electrolytes, and stress-dose hydrocortisone usage. Results CAH youth had more frequent illnesses requiring stress-dosing when they were younger than 2 years old [4.0 (1.0-6.0)] compared to when they were 2-4 years old [3.0 (1.0-4.0), P < 0.05], with the most illnesses during their first year of life. As well, CAH infants and toddlers had more hospitalizations younger than 2 years old compared to 2-4 years old (36 vs 2). 25% (3/12) of CAH youth with abnormal electrolytes in the ED did not receive any stress-dosing (oral/IM) prior to the ED, and only 25% (3/12) had received intramuscular hydrocortisone at home. CAH youth had more frequent ED visits (7.4 times as many) and hospitalizations (38 to 0) compared to controls. Conclusions Very young children with classical CAH are at high risk for acute illness and hospitalizations during their first 2 years of life, and do not receive adequate stress-dosing prior to the ED despite appropriate education. Our findings underscore the need for earlier recognition of acute illness in this vulnerable population and improved education regarding administration of stress-dose hydrocortisone to prevent morbidity.", "URL": "https://doi.org/10.1101/19005462"} |
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] | {"Title": "Post-discharge Acute Care and Outcomes in the Era of Readmission Reduction", "Authors": "Khera Rohan, Wang Yongfei, Bernheim Susannah M., Lin Zhenqiu, Krumholz Harlan M.", "Abstract": "ABSTRACT Background With incentives to reduce readmission rates, there are concerns that patients who need hospitalization after a recent hospital discharge may be denied access, which would increase their risk of mortality. Objective We determined whether patients with hospitalizations for conditions covered by national readmission programs who received care in emergency department (ED) or observation units but were not hospitalized within 30 days had an increased risk of death. We also evaluated temporal trends in post-discharge acute care utilization in inpatient units, emergency department (ED) and observation units for these patients. Design, Setting, and Participants In this observational study, national Medicare claims data for 2008-2016, we identified patients \u226565 years hospitalized with heart failure (HF), acute myocardial infarction (AMI), or pneumonia, conditions included in the HRRP. Main Outcomes and Measures Post-discharge 30-day mortality according to patients\u2019 30-day acute care utilization. Acute care utilization in inpatient and observation units, and the ED during the 30-day and 31-90-day post-discharge period. Results There were 3,772,924 hospitalizations for HF, 1,570,113 for AMI, and 3,131,162 for pneumonia. The overall post-discharge 30-day mortality was 8.7% for HF, 7.3% for AMI, and 8.4% for pneumonia. Post-discharge mortality increased annually by 0.16% (95% CI, 0.11%, 0.22%) for HF, decreased by 0.15% (95% CI, -0.18%, -0.12%) for AMI, and did not significantly change for pneumonia. Specifically, mortality only increased for HF patients who did not utilize any post-discharge acute care, increasing at a rate of 0.16% per year (95% CI, 0.11%, 0.22%), accounting for 99% of the increase in post-discharge mortality in heart failure. Concurrent with a reduction in 30-day readmission rates, 30-day observation stays and visits to the ED increased across all 3 conditions during and beyond the post-discharge 30-day period. There was no significant change in overall 30-day post-acute care utilization (P-trend >0.05 for all). Conclusions and Relevance The only condition with an increasing mortality through the study period was HF; the increase preceded the policy and was not present among those received ED or observation unit care without hospitalization. Overall, during this period, there was not a significant change in the overall 30-day post-discharge acute care utilization.", "URL": "https://doi.org/10.1101/19002162"} |
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] | {"Title": "Causal mediation analysis of Subclinical Hypothyroidism in children with obesity and Non-Alcoholic Fatty Liver Disease", "Authors": "Nichols Presley, Pan Yue, May Benjamin, Pavlicova Martina, Mencin Ali, Thaker Vidhu V", "Abstract": "Abstract Context Nonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity and a leading cause of liver disease in children. Subclinical hypothyroidism (SH) occurs with obesity and may contribute to dysmetabolic state that predisposes to NAFLD. Objective To assess the relationship between SH and NAFLD in children with biopsy-proven NAFLD compared to controls. Design and Methods In this retrospective study of cases from a registry of children with biopsy-proven NAFLD and age-matched controls, the association of SH with NAFLD and other cardiometabolic parameters was assessed followed by causal mediation analyses under the counter-factual framework. Results Sixty-six cases and 4067 age-matched controls were included in the study. Children with NAFLD were more likely to be male (74.6 vs 39.4%, p < 0.001), have higher modified BMI-z scores (2.3 \u00b11.6 vs 1\u00b11.6, p < 0.001), and abnormal metabolic parameters (TSH, ALT, HDL-C, non-HDL-C, LDL-C, and TG). Multivariate analyses controlling for age, sex and severity of obesity showed significant association between the 4 th quartile of TSH and NAFLD. Causal mediation analysis demonstrates that TSH mediates 44% of the effect of modified BMI-z score on NAFLD. This comprises of 16.2% (OR = 1.1, p < 0.001) caused by the indirect effect of TSH and its interaction with modified BMI-z, and 26.5% (OR = 1.1, p = 0.01) as an autonomous effect of TSH on NAFLD regardless of the obesity. Conclusions The association of SH and biopsy-proven NAFLD is demonstrated in a predominately Latino population. Further, a causal mediation analysis implicates an effect of TSH on NAFLD, independent of obesity.", "URL": "https://doi.org/10.1101/19004242"} |
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] | {"Title": "Machine learning to predict early recurrence after oesophageal cancer surgery", "Authors": "Rahman Saqib A, Walker Robert C, Lloyd Megan A, Grace Ben L, van Boxel Gijs I, Kingma Feike, Ruurda Jelle P, van Hillegersberg Richard, Harris Scott, Parsons Simon, Mercer Stuart, Griffiths Ewen A, O\u2019Neill J.Robert, Turkington Richard, Fitzgerald Rebecca C, Underwood Timothy J", "Abstract": "ABSTRACT Objective To develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multi-national cohort. Summary Background Data Early cancer recurrence after oesophagectomy is a common problem with an incidence of 20-30% despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. Machine learning techniques potentially allow more accurate prognostication and have been applied in this study. Methods Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in 6 UK and 1 Dutch oesophago-gastric units were analysed. Using clinical characteristics and post-operative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and XG boost (XGB). Finally, a combined (Ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. Results In total 812 patients were included. The recurrence rate at less than 1 year was 29.1%. All of the models demonstrated good discrimination. Internally validated AUCs were similar, with the Ensemble model performing best (ELR=0.785, RF=0.789, XGB=0.794, Ensemble=0.806). Performance was similar when using internal-external validation (validation across sites, Ensemble AUC=0.804). In the final model the most important variables were number of positive lymph nodes (25.7%) and vascular invasion (16.9%). Conclusions The derived model using machine learning approaches and an international dataset provided excellent performance in quantifying the risk of early recurrence after surgery and will be useful in prognostication for clinicians and patients. DRAFT VISUAL ABSTRACT Icons taken from www.flaticon.com , made by \u2018Freepik\u2019, \u2018smashicons\u2019, and \u2018prettycons\u2019. Reproduced under creative commons attribution license MINI-ABSTRACT Early recurrence after surgery for adenocarcinoma of the oesophagus is common. We derived a risk prediction model using modern machine learning methods that accurately predicts risk of early recurrence using post-operative pathology", "URL": "https://doi.org/10.1101/19001073"} |
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] | {"Title": "Personalized Connectome Mapping to Guide Targeted Therapy and Promote Recovery of Consciousness in the Intensive Care Unit", "Authors": "Edlow Brian L., Barra Megan E., Zhou David W., Snider Samuel B., Threlkeld Zachary D., Kirsch John E., Chan Suk-tak, Meisler Steven L., Bleck Thomas P., Fins Joseph J., Giacino Joseph T., Hochberg Leigh R., Solt Ken, Brown Emery N., Bodien Yelena G.", "Abstract": "Abstract There are currently no therapies proven to promote early recovery of consciousness in patients with severe brain injuries in the intensive care unit (ICU). Early recovery of consciousness would benefit patients and families by reducing the likelihood of premature withdrawal of life-sustaining therapy and may decrease ICU complications related to immobility, facilitate self-expression, enable autonomous decision-making, and increase access to rehabilitative care. Here, we present the connectome-based clinical trial platform (CCTP), a new mechanistic paradigm for developing and testing targeted therapies that promote early recovery of consciousness in the ICU. The scientific premise of the CCTP is that personalized brain connectome maps can be used to select patients for targeted therapies that promote recovery of consciousness. Structural and functional MRI connectome maps will identify circuits that may be amenable to neuromodulation. Patients will be selected for clinical trials in the CCTP paradigm based on connectomes that are likely to respond to targeted therapies. To demonstrate the utility of this precision approach, we describe STIMPACT ( S timulant T herapy Targeted to Individualized Connectivity M aps to P romote Re ACT ivation of Consciousness), a CCTP-based clinical trial in which intravenous methylphenidate will be used to promote early recovery of consciousness in the ICU (ClinicalTrials.gov NCT03814356). We propose that the CCTP has the potential to transform the therapeutic landscape in the ICU and improve outcomes for patients with severe brain injuries.", "URL": "https://doi.org/10.1101/19013987"} |
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] | {"Title": "PROBLEM BASED LEARNING APPLIED TO PRACTICE IN MEDICAL SCHOOLS IN BRAZIL: A MINI-SYSTEMATIC REVIEW", "Authors": "Bussolaro Frederico Alberto, Thereza-Bussolaro Claudine", "Abstract": "ABSTRACT Background Active learning is a well-established educational methodology in medical schools worldwide, although its implementation in Brazilian clinical settings is quite challenging. The objective of this study is to review the literature in a systematic manner to find and conduct a reflective analysis of how problem-based learning (PBL) has been applied to clinical teaching in medical schools in Brazil. Material & methods A systematic literature search was conducted in three databases. A total of 250 papers related to PBL in Brazilian medical schools were identified through the database searches. Four studies were finally selected for the review. Results Four fields of medicine were explored on the four selected papers: gynecology/family medicine, medical semiology, psychiatry, and pediatrics. Overall, all the papers reported some level of strategic adaptability of the original PBL methodology to be applied in the Brazilian medical school\u2019s curricula and to the peculiar characteristics specific to Brazil. Conclusion PBL application in Brazilian medical schools require some level of alteration from the original format, to better adapt to the characteristics of Brazilian students\u2019 maturity, health system priorities and the medical labor market.", "URL": "https://doi.org/10.1101/19007955"} |
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] | {"Title": "Predictors of health related quality of life among diabetic patients on follow up at Nekemte Specialized Hospital, Western Ethiopia: A cross sectional study", "Authors": "Feyisa Bikila Regassa, Yilma Mekdes Tigistu, Tolessa Belachew Etana", "Abstract": "Abstract Objective To assess health related quality of life (HRQoL) and its predictors among diabetic patients on follow up at Nekemte Specialized Hospital (NSH) in Western Ethiopia. Design, setting and participants This facility based cross sectional study was conducted among 224 diabetic patients on follow up at one of the public hospitals in western Ethiopia. Main outcome measured HRQoL was measured by using the Medical Outcome Study 36-item Short Form Health Survey from 15 th April to 5 th June. Structured questionnaire was used for data the collection from participants selected by systematic random sampling. Multiple linear regression was used for final model. Result A total of 215 diabetic patients were involved in the study with the response rate of 96%. The mean score of the overall HRQoL of the study participants was found to be 50.30 \u00b1 18.08 with highest mean score in physical functioning and lowest mean score in general health domain. Age, education status, history of smoking, feeling of stigmatized and Body mass index (BMI) were inversely associated while being male, being married, absence of co morbidity and absence of chronic complications related to diabetes mellitus were found to be positively associated with overall HRQoL. Conclusion The overall HRQoL of diabetic patients on follow up at the study area was found to be moderate. General health, mental health, bodily pain and vitality were the most affected domains. Both the mental and physical components need to be considered when caring the diabetic patients on follow up beyond provision of treatment. Strength and limitations of this study The study was the first of its kind in assessing the predictors of health-related quality of life (HRQoL) among both diabetes mellitus type I and type II in Ethiopia. The tools used was validated across different cultures Eight domains of HRQoL and two component summary scores were used to make the measurement more specific. The cross sectional nature of the study design made the result of the study difficult to identify either the cause or the effect comes first.", "URL": "https://doi.org/10.1101/19013516"} |
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] | {"Title": "DNA methylation biomarker selected by an ensemble machine learning approach predicts mortality risk in an HIV-positive veteran population", "Authors": "Shu Chang, Justice Amy C., Zhang Xinyu, Marconi Vincent C., Hancock Dana B., Johnson Eric O., Xu Ke", "Abstract": "Abstract Background With the improved life expectancy of people living with HIV (PLWH), identifying vulnerable subpopulations at high risk of mortality is important for clinical care. Evidences showed that DNA methylation (DNAm) is associated with aging and mortality in non-HIV populations. Here, we aimed to establish a panel of DNAm biomarkers that can predict mortality risk among PLWH. Methods 1,081 HIV-positive participants from the Veterans Aging Cohort Study (VACS) were divided into training (N=460), validation (N=114), and testing (N=507) sets. VACS index was used as a measure of mortality risk among PLWH. Model training and fine-tuning were conducted using the ensemble method in the training and validation sets and prediction performance was assessed in the testing set. The survival analysis comparing the predicted high and low mortality risk groups was conducted. The Gene Ontology enrichment analysis of the predictive CpG sites was performed. Results We selected a panel of 393 CpGs for the ensemble prediction model. The prediction model showed excellent performance in predicting high mortality risk with an auROC of 0.809 (95%CI: 0.767-0.851) and a balanced accuracy of 0.653 (95%CI: 0.611, 0.693) in the testing set. The predicted high mortality risk group was significantly associated with 10-year mortality (hazard ratio=1.79, p=4E-05) compared with low mortality risk group. These 393 CpGs were located in 280 genes enriched in immune and inflammation responses pathways. Conclusions We identified a panel of DNAm features associated with mortality risk in PLWH. These DNAm features may serve as predictive biomarkers for mortality risk among PLWH.", "URL": "https://doi.org/10.1101/19010272"} |
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] | {"Title": "Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study", "Authors": "David Szabolcs, Mesri Hamed Y., Bodiut Victor A., Nagtegaal Steven H. J., Elhalawani Hesham, de Luca Alberto, Philippens Marielle E. P., Viergever Max A., Mohamed Abdallah S. R., Ding Yao, Chung Caroline, Fuller Clifton D., Verhoeff Joost J. C., Leemans Alexander", "Abstract": "Abstract Background and purpose Radiation-induced changes in brain tissue may relate to post-radiotherapy (RT) cognitive decline. Our aim is to investigate changes of the brain microstructural properties after exposure to radiation during clinical protocols of RT using diffusion MRI (dMRI). Methods and Materials The susceptibility of tissue changes to radiation was investigated in a clinically heterogenic cohort (age, pathology, tumor location, type of surgery) consisting of 121 scans of 18 patients (10 females). The imaging dataset included 18 planning CTs and 103 dMRI scans (range 2-14, median = 6 per patient) assessing pre-operative, post-operative pre-RT and post-RT states. Diffusion tensor imaging (DTI) metrics were estimated from all scans for a region-of-interest based linear relation analysis between mean dose and change in DTI metrics, while partial volume effects were regressed out. Results The largest regional dose dependency with mean diffusivity appear in the white matter of the frontal pole in the left hemisphere by an increase of 2.61 %/(Gy x year). Full brain-wise, pooled results for white matter show fractional anisotropy to decrease by 0.85 %/(30Gy x year); mean diffusivity increase by 9.17 %/(30Gy x year); axial diffusivity increase by 7.30%/(30Gy x year) and radial diffusivity increases by 10.63%/(30Gy x year). Conclusions White matter is susceptible to radiation with some regional variability where diffusivity metrics demonstrate the largest relative sensitivity. This suggests that dMRI is a promising tool in assessing microstructural changes after RT, which can help in understanding treatment-induced cognitive decline.", "URL": "https://doi.org/10.1101/19005157"} |
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] | {"Title": "Influenza-associated mortality for different causes of death during the 2010-2011 through the 2014-2015 influenza seasons in Russia", "Authors": "Goldstein Edward", "Abstract": "Abstract Background There is limited information on the volume of influenza-associated mortality in Russia. Methods Using previously developed methodology (Goldstein et al., Epidemiology 2012), we regressed the monthly rates of mortality for respiratory causes, circulatory causes, and for certain infectious and parasitic diseases (available from the Russian Federal State Statistics Service (Rosstat)) linearly against the monthly proxies for the incidence of influenza A/H3N2, A/H1N1 and B (obtained using data from the Smorodintsev Research Institute of Influenza (RII) on levels of ILI/ARI consultations and the percent of respiratory specimens testing positive for influenza A/H3N2, A/H1N1 and B), adjusting for the baseline rates of mortality not associated with influenza circulation and temporal trends. Results For the 2010/11 through the 2014/15 seasons, influenza circulation was associated with an average annual 11106 (95% CI (4321,17892)) deaths for circulatory causes, 4552 (3744,5360) deaths for respiratory causes, and 343 (63,624) deaths for certain infectious and parasitic diseases, with influenza A/H3N2 being responsible for the majority of influenza-associated respiratory deaths and influenza B making a substantial contribution to influenza-associated mortality for circulatory causes. Conclusions Influenza circulation is associated with a substantial mortality burden in Russia, particularly for circulatory deaths. Those results support the potential utility of influenza vaccination (with the role played by influenza B in circulatory mortality pointing to the benefit of quadrivalent influenza vaccines), as well as of administration of antiviral drugs for high-risk individuals during periods of active influenza circulation.", "URL": "https://doi.org/10.1101/19005470"} |
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] | {"Title": "Reliability and validity of the UK Biobank cognitive tests", "Authors": "Fawns-Ritchie Chloe, Deary Ian J", "Abstract": "Abstract UK Biobank is a health resource with data from over 500,000 adults. The participants have been assessed on cognitive function since baseline. The cognitive tests in UK Biobank are brief and bespoke, and are administered without supervision on a touchscreen computer. Psychometric information on the tests is limited. The present study examined their concurrent validity and short-term test-retest reliability. A sample of 160 participants (mean age=62.59, SD=10.24) completed the UK Biobank cognitive assessment and a range of well-validated cognitive tests (\u2018reference tests\u2019). Fifty-two participants returned 4 weeks later to repeat the UK Biobank tests. Correlations were calculated between UK Biobank tests and the reference tests. Four-week test-retest correlations were calculated for UK Biobank tests. UK Biobank cognitive tests showed a range of correlations with their respective reference tests, i.e. those tests that are thought to assess the same underlying cognitive ability (mean Pearson r =0.53, range=0.22 to 0.83, p \u2264.005). Four-week test-retest reliability of the UK Biobank tests were moderate-to-high (mean Pearson r =0.55, range=0.40 to 0.89, p\u2264.003). Despite the brief, non-standard nature of the UK Biobank cognitive tests, some showed substantial concurrent validity and test-retest reliability. These psychometric results provide currently-lacking information on the validity of the UK Biobank cognitive tests.", "URL": "https://doi.org/10.1101/19002204"} |
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] | {"Title": "Applications of qualitative grounded theory methodology to investigate hearing loss: Protocol for a qualitative systematic review", "Authors": "Ali Yasmin H K, Wright Nicola, Charnock David, Henshaw Helen, Ferguson Melanie A, Hoare Derek J", "Abstract": "ABTRACT Introduction Hearing loss is a chronic condition affecting 11 million individuals in the UK. People with hearing loss regularly experience difficulties interacting in everyday conversations. These difficulties in communication can result in a person with hearing loss withdrawing from social situations and becoming isolated. While hearing health loss research has largely deployed quantitative methods to investigate various aspects of the condition, qualitative research is becoming more widespread. Grounded theory is a specific qualitative methodology that has been used to establish novel theories on the experiences of living with hearing loss. Method and analysis The aim of this systematic review is to establish how grounded theory has been applied to investigate the psychosocial aspects of hearing loss. Methods are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) 2015 checklist. Studies included in this review will have applied grounded theory methodology. For a study to be included, it can apply grounded theory as an overarching methodology, or have grounded theory methodology embedded amongst other methodologies. These studies can be in the form of retrospective or prospective studies, before and after comparison studies, RCTs, non-RCTs, cohort studies, prospective observational studies, case-control studies, cross-sectional studies, longitudinal studies, and mixed method studies. Purely quantitative studies, studies that have not applied grounded theory methodology, articles reporting expert opinions, case reports, practice guidelines, case series, conference abstracts, and book chapters will be excluded. Studies included will have adult participants (\u226518 years) who are either people with an acquired hearing loss, their family and friends (communication partners), or audiologists. The quality of application of grounded theory in each study will be assessed using the Guideline for Reporting and Evaluating Grounded Theory Research Studies (GUREGT). Ethics and dissemination As only secondary data will be used in this systematic review, ethical approval is not required. No other ethical issues are foreseen. The International Prospective Register of Systematic Reviews ( http://www.crd.york.ac.uk/PROSPERO ) holds the registration record of this systematic review. Findings will be disseminated via peer reviewed publications and at relevant academic conferences. Findings may also be published in relevant professional and third sector newsletters and magazines as appropriate. Data will inform future research and guideline development. Prospero registration number PROSPERO CRD42019134197 Strengths and limitations of this study This systematic review is the first to provide a comprehensive critique of the use of grounded theory to investigate hearing loss. The search strategy was formed in collaboration with an information specialist at the University of Nottingham. The PRISMA-P guidelines have directed the considerations and layout of this protocol. Because experiences and articulations of hearing loss are influenced by age, only adult (\u226518 years) participants (people with hearing loss, communication partners, audiologists) will be considered. The search will not include grey literature. The studies included will only have samples of individuals with hearing loss, rather than full deafness.", "URL": "https://doi.org/10.1101/19004259"} |
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] | {"Title": "Genetic Diversity of the cagA gene of Helicobacter pylori strains from Sudanese Patients with Different Gastroduodenal Diseases", "Authors": "Hassan Hadeel Gassim, Idris Abeer Babiker, Hassan Mohamed A., Altayb Hisham N., Yasin Kyakonye, Beirage Nazar, Abdel Hamid Muzamil M.", "Abstract": "Abstract Background There is an increase in the prevalence of Helicobacter pylori infection in Sudan, accompanied by a high incidence of upper gastrointestinal malignancy. The cytotoxin-associated gene cagA gene is a marker of a pathogenicity island (PAI) in H. pylori and plays a crucial role in determining the clinical outcome of Helicobacter infections. Objective This study aimed to determine the frequency and heterogeneity of the cagA gene of H. pylori and correlate the presence of cagA gene with clinical outcomes. Materials and methods Fifty endoscopy biopsies were collected from Fedail and Soba hospitals in Khartoum state. DNA was extracted using the Guanidine chloride method followed by PCR to amplify 16S rRNA and cagA gene of H. pylori using specific primers. DNA amplicons of cagA gene were purified and sequenced. Bioinformatics and statistical analysis were done to characterize and to test the association between cagA gene and gastric complications. Results CagA gene was detected in 20/37(54%) of the samples that were found positive for H. pylori . There was no association between endoscopy finding and the presence of the cagA gene (p = 0.225). Specific amino acid variations were found at seven loci related to strains from a patient with duodenitis, gastric ulcer, and gastric atrophy (R448H, T457K, S460L, IT463-464VA, D470E, A482Q, KNV490-491-492TKT) while mutations in cancerous strain were A439P, T457P, and H500Y. Conclusion Disease-specific variations of cagA of H. pylori strains, in the region of amino acid residues 428-510, were evident among Sudanese patients with different gastroduodenal diseases. A novel mutation (K458N) was detected in a patient with duodenitis, which affects the positive electrostatic surface of cagA . Phylogenetic analysis showed a high level of diversity of cagA from Sudanese H. pylori strains.", "URL": "https://doi.org/10.1101/19007435"} |
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] | {"Title": "The consistent burden in published estimates of delirium occurrence in medical inpatients over four decades: a systematic review and meta-analysis study", "Authors": "Gibb Kate, Seeley Anna, Quinn Terry, Siddiqi Najma, Shenkin Susan, Rockwood Kenneth, Davis Daniel", "Abstract": "Abstract Introduction Delirium is associated with a wide range of adverse patient safety outcomes. We sought to identify if trends in healthcare complexity were associated with changes in reported delirium in adult medical patients in the general hospital over the last four decades. Methods We used identical criteria to a previous systematic review, including studies using DSM and ICD-10 criteria for delirium diagnosis. Random effects meta-analysis pooled estimates across studies, meta-regression estimated temporal changes, funnel plots assessed publication bias. Results Overall delirium occurrence was 23% (95% CI 19%-26%) (33 studies). There was no change between 1980-2019, nor was case-mix (average age of sample, proportion with dementia) different. There was evidence of increasing publication bias over time. Discussion The incidence and prevalence of delirium in hospitals appears to be stable, though publication bias may mask true changes. Nonetheless, delirium remains a challenging and urgent priority for clinical diagnosis and care pathways.", "URL": "https://doi.org/10.1101/19005165"} |
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] | {"Title": "HIV-1 founder variant multiplicity is determined by the infection stage of the source partner", "Authors": "Villabona-Arenas Ch. Juli\u00e1n, Hall Matthew, Lythgoe Katrina A., Gaffney Stephen G., Regoes Roland R., Hu\u00e9 St\u00e9phane, Atkins Katherine E.", "Abstract": "Abstract During sexual transmission, the large genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection 1 . Understanding the drivers of this bottleneck is crucial to develop effective infection control strategies 2 . Genetic characteristics of the potential founder viruses and events in the recipient partner are both known to contribute to this bottleneck, but little is understood about the importance of the source partner 3 . To test the hypothesis that the source partner affects the multiplicity of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results demonstrate the importance of infection stage of the source partner, and not exposure route, in determining founder variant multiplicity. Specifically, acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple variant transmission when compared with someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple founder strain infections and can inform clinical intervention study design and interpretation.", "URL": "https://doi.org/10.1101/19013524"} |
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] | {"Title": "Forecasting the impact of population ageing on tuberculosis incidence", "Authors": "Ku Chu-Chang, Dodd Peter J", "Abstract": "Abstract Background Tuberculosis (TB) disease reactivates from distant latent infection or recent (re)infection. Progression risks increase with age. Across the World Health Organisation Western Pacific region, many populations are ageing and have the highest per capita TB incidence rates in older age groups. However, methods for analysing age-specific TB incidence and forecasting epidemic trends while accounting for demographic change remain limited. Methods We applied the Lee-Carter models, which were originally developed for mortality modelling, to model the temporal trends in age-specific TB incidence data from 2005 to 2018 in Taiwan. Females and males were modelled separately. We combined our demographic forecasts, and age-specific TB incidence forecasts to project TB incidence until 2035. We compared TB incidence projections with demography fixed in 2018 to projections accounting for demographic change. Results Our models quantified increasing incidence rates with age and declining temporal trends. By 2035, the forecast suggests that the TB incidence rate in Taiwan will decrease by 54% (95% Prediction Interval (PI): 45%-59%) compared to 2015, while most age-specific incidence rates will reduce by more than 60%. In 2035, adults aged 65 and above will make up 78% of incident TB cases. Forecast TB incidence in 2035 accounting for demographic change will be 39% (95% PI: 36%-42%) higher than without population ageing. Conclusions Age-specific incidence forecasts coupled with demographic forecasts can inform the impact of population ageing on TB epidemics. The TB control programme in Taiwan should develop plans specific to older age groups and their care needs.", "URL": "https://doi.org/10.1101/19001115"} |
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] | {"Title": "Using Paired Agent-Based Simulations To Test Strategies For Limiting The Effects Of Epidemics", "Authors": "Armstrong Margaret, Coelho Fl\u00e1vio Code\u00e7o", "Abstract": "Abstract Agent-based simulations are widely used nowadays in public health research for comparing different strategies for mitigating epidemics and for planning appropriate responses in the aftermath of crises in large urban areas because they can capture fine scale heterogeneities that may have important non-linear effects on the results. Given the costs of implementing strategies, decision-makers have to be convinced that the proposed treatment/procedure leads to a statistically significant improvement. This paper presents an innovative method for constructing paired agent-based simulations where exactly the same set of random effects is applied to simulations with and without the treatment/procedure. Statistical Analysis of Variance distinguishes the sum of squares between groups (BSS) from the sum of squares within groups (WSS). Our aim was to filter out the within sum of squares (WSS) leaving only the sum of squares between the control group and the treatment group (BSS). We propose to filter out the WSS by constructing paired simulations because as is well known, when paired t-tests can be used, they are much more powerful than ordinary t-tests. Pearson\u2019s Chi-squared goodness of fit, the Kolmogorov-Smirnov statistic and the Kullback-Leibler Divergence are then used to test whether the effect is statistically significant. This procedure has been tested on a case-study on the propagation of the Zika epidemic in Rio de Janeiro in 2015. Author summary Agent-based simulations are emerging as a powerful tool in computational biology because they can capture fine scale heterogeneities that can have important effects on the propagation of epidemics. In silico experiments can be used to test different strategies for mitigating epidemics quickly and inexpensively. Given the inherent variability from one simulation to another, it is difficult to statistically prove their effectiveness. We have developed a powerful method rather like paired t-tests, for testing whether a given treatment is statistically better than the control. We do this by generating paired simulations with exactly the same random variables in the control simulation and the one with a treatment. Using the terminology of analysis of variance, we want to filter out the sum of squares within the group, leaving only the sum of squares between the control and the treatment. This procedure has been applied to a case-study to see whether enclosing and air-conditioning the transport hub in Rio de Janeiro would have slowed down the propagation of Zika.", "URL": "https://doi.org/10.1101/19014043"} |
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] | {"Title": "Comparative functional survival and equivalent annual cost of three long lasting insecticidal net (LLIN) products in Tanzania", "Authors": "Lorenz Lena M, Bradley John, Yukich Joshua, Massue Dennis Joram, Mboma Zawadi Mageni, Pigeon Olivier, Moore Jason, Kilian Albert Dr., Lines Jo, Kisinza William, Overgaard Hans J, Moore Sarah J", "Abstract": "Abstract Almost 1.2 billion long-lasting insecticidal nets (LLINs) have been procured for malaria control. Institutional buyers often assume that World Health Organization (WHO) prequalified LLINs are functionally identical with a three-year lifespan. We measured the lifespans of three LLIN products, and calculated their cost-per-year of functional life, through a randomised double-blinded prospective evaluation among 3,420 study households in Tanzania using WHO-recommended methods. Primary outcome was LLIN functional survival (LLINs present in serviceable condition). Secondary outcomes were 1) bioefficacy and chemical content (residual insecticidal activity) and 2) protective efficacy for volunteers sleeping under LLINs (bite reduction and mosquitoes killed). LLIN median functional survival was significantly different: 2\u00b70 years for Olyset, 2\u00b75 years for PermaNet and 2\u00b76 years for NetProtect. Functional survival was affected by accumulation of holes resulting in users discarding nets. Protective efficacy also significantly differed between products as they aged. The longer-lived nets were 20% cheaper than the shorter-lived product.", "URL": "https://doi.org/10.1101/19002212"} |
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] | {"Title": "Treatment advantage in HBV/HIV coinfection compared to HBV monoinfection in a South African cohort", "Authors": "Maponga Tongai G, McNaughton Anna L, Van Schalkwyk Marije, Hugo Susan, Nwankwo Chikezie, Taljaard Jantjie, Mokaya Jolynne, Smith David A, van Vuuren Cloete, Goedhals Dominique, Gabriel Shiraaz, Andersson Monique I, Preiser Wolfgang, van Rensburg Christo, Matthews Philippa C", "Abstract": "ABSTRACT Objective Prompted by international targets for elimination of hepatitis B virus (HBV) infection, we performed a cross-sectional observational study of adults with chronic HBV (CHB) infection in South Africa, characterising individuals with HBV monoinfection vs. those coinfected with HBV/HIV, to evaluate the impact of therapy and to guide improvements in clinical care as guidelines for antiviral therapy change over time. Design We prospectively recruited 115 adults with CHB, over a period of one year at a university hospital in Cape Town, South Africa. HIV coinfection was present in 39 (34%) subjects. We recorded cross-sectional demographic, clinical and laboratory data. Results Adults with HBV monoinfection were comparable to those with HBV/HIV coinfection in terms of age, sex and body mass. HBeAg-positive status was more common among those with HIV coinfection (p=0.01). However, compared to HBV/HIV coinfection, HBV monoinfected patients were less likely to have had assessment with elastography (p<0.0001) and less likely to be on antiviral treatment (p<0.0001). The HBV monoinfected group was more likely to have detectable HBV viraemia (p=0.04), and features suggesting underlying liver disease including moderate/severe thrombocytopaenia (p=0.007), elevated bilirubin (p=0.004), and APRI score >2 (p=0.02). Three cases of hepatocellular carcinoma were documented, all in patients with HBV monoinfection. Conclusion In this setting, individuals with HBV monoinfection are disadvantaged in terms of clinical assessment and appropriate antiviral therapy compared to those with HIV coinfection, associated with relatively worse liver health. Enhanced advocacy, education, resources and infrastructure are required to optimise interventions for CHB.", "URL": "https://doi.org/10.1101/19007963"} |
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] | {"Title": "A Comparison of Contemporary versus Older Studies of Aspirin for Primary Prevention", "Authors": "Moriarty Frank, Ebell Mark H.", "Abstract": "Abstract Objective This study compares the benefits and harms of aspirin for primary prevention before and after widespread use of statins and colorectal cancer screening. Methods We compared studies of aspirin for primary prevention that recruited patients from 2005 onward with previous individual patient meta-analyses that recruited patients from 1978 to 2002. Data for contemporary studies were synthesized using random-effects models. We report vascular (major adverse cardiovascular events [MACE], myocardial infarction [MI], stroke), bleeding, cancer, and mortality outcomes. Results The IPD analyses of older studies included 95,456 patients for CV prevention and 25,270 for cancer mortality, while the four newer studies had 61,604 patients. Relative risks for vascular outcomes for older vs newer studies follow: MACE: 0.89 (95% CI 0.83-0.95) vs 0.93 (0.86-0.99); fatal hemorrhagic stroke: 1.73 (1.11-2.72) vs 1.06 (0.66-1.70); any ischemic stroke: 0.86 (0.74-1.00) vs 0.86 (0.75-0.98); any MI: 0.84 (0.77-0.92) vs 0.88 (0.77-1.00); and non-fatal MI: 0.79 (0.71-0.88) vs 0.94 (0.83-1.08). Cancer death was not significantly decreased in newer studies (RR 1.11, 0.92-1.34). Major hemorrhage was significantly increased for both older and newer studies (RR 1.48, 95% CI 1.25-1.76 vs 1.37, 95% CI 1.24-1.53). There was no effect in either group on all-cause mortality, cardiovascular mortality, fatal stroke, or fatal MI. Conclusions In the modern era characterized by widespread statin use and cancer screening, aspirin does not reduce the risk of non-fatal MI or cancer death. There are no mortality benefits and a significant risk of major hemorrhage. Aspirin should no longer be recommended for primary prevention. Summary of current evidence and what this study adds What is already known about this subject? The cumulative evidence for aspirin suggests a role in the primary prevention of cardiovascular disease, and in reducing cancer incidence and mortality. However most of the trials of aspirin for primary prevention were set in Europe and the United States and recruited patients prior to the year 2000. The benefits and harms of aspirin should be considered separately in studies performed in the eras before and after widespread use of statins and colorectal cancer screening. What does this study add? This study provides the most detailed summary to date of cardiac, stroke, bleeding, mortality and cancer outcomes to date in the literature. In trials of aspirin for primary prevention from 2005 onwards, aspirin reduced major adverse cardiovascular events but significantly increased the risk of bleeding, with no benefit for mortality or, Unlike older studies, there was no reduction in cancer mortality and non-fatal myocardial infarction. How does this impact on clinical practice? Our study suggests aspirin should not be recommended for primary prevention in the modern era.", "URL": "https://doi.org/10.1101/19004267"} |
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] | {"Title": "Brain derived neurotrophic factor (BDNF) Val66Met polymorphism is not risk factor for bipolar disorder", "Authors": "Rai Vandana, Jamal Farhin, Kumar Pradeep", "Abstract": "Abstract Bipolar disorder (BPD) is a psychiatric disease, characterized by the cycles of mania and depression. Several genetic studies investigated BDNF gene Val66Met polymorphism as risk factor for BPD, but results were inconclusive. Therefore, present meta-analysis was performed to reevaluate the BDNF Val66Met polymorphism and BPD association. Four databases (Pubmed, Springer Link, Science Direct and Google Scholar) were searched for eligible studies up to March 31,2018. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of the association. All statistical analyses were done by MetaAnalyst and Mix program. Forty studies with a total of 28,787 subjects (10,085 cases and 18,702 controls) were included in this meta-analysis. Overall, pooled analysis indicated that there was no significant association between BDNF Val66Met polymorphism and BPD risk under all five genetic models (OR A vs.G =0.99, 95%CI= 0.94-1.03, p=0.49; OR AG vs. GG = 0.1.02, 95%CI= 0.95-1.07, p= 0.57; OR AA vs. GG = 0.98, 95%CI=0.89-1.08, p=0.75; OR AA+AG vs. GG = 1.0, 95%CI= 0.94-1.06, p= 0.89;OR AA vs. AG+GG = 0.96, 95%CI= 0.89-1.05, p= 0.47). Similarly, no significant association was observed in ethnicity based subgroup analysis in both Asian and Caucasian population. However, significant association was found in subtype analysis between BDNF Val66Met and BPDII (OR AA+AG vs. GG = 1.21, 95%CI= 1.06-1.37, p= 0.003) but not with BPDI. These findings suggested that the BDNF Val66Met polymorphism confer no genetic susceptibility to BPD I but risk for BPDII.", "URL": "https://doi.org/10.1101/19010280"} |
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] | {"Title": "Epigenetic prediction of major depressive disorder", "Authors": "Barbu Miruna C., Walker Rosie M., Howard David M., Evans Kathryn L., Whalley Heather C., Porteous David J., Morris Stewart W., Deary Ian J., Marioni Riccardo E., Clarke Toni-Kim, McIntosh Andrew M.", "Abstract": "Abstract Objective DNA methylation (DNAm) is associated with environmental risk factors for major depressive disorder (MDD) but has not yet been tested for its ability to discriminate individuals with MDD from unaffected individuals. Methods Using penalized regression based on genome-wide CpG methylation, we trained a DNAm risk score of MDD (DNAm-RS) in 1,223 cases and 1,824 controls and tested in a second independent sample of 363 prevalent cases and 1,417 controls. Using DNA from 1,607 unaffected individuals, we tested whether DNAm-RS could discriminate the 190 incident cases of lifetime MDD from the 1,417 individuals who remained unaffected at follow-up. Results A weighted linear combination of 196 CpG sites were derived from the training sample to form a DNAm-RS. The DNAm-RS explained 1.75% of the variance in MDD risk in an independent case-control sample and significantly predicted future incident episodes of MDD at follow up (R 2 =0.52%). DNAm-RS and MDD polygenic risk scores together additively explained 3.99% of the variance in prevalent MDD. The DNAm-RS was also significantly associated with lifestyle factors associated with MDD, including smoking status (\u03b2=0.440, p=<2\u00d710 \u221216 ) and alcohol use (\u03b2=0.092, p=9.85\u00d710 \u22125 ). The DNAm-RS remained significantly associated with MDD after adjustment for these environmental factors (independent association: \u03b2=0.338, p=1.17\u00d710 \u22127 association post-adjustment: \u03b2=0.081, p=0.0006). Conclusions A novel risk score of MDD based on DNAm data significantly discriminated MDD cases from controls in an independent dataset, and controls who would subsequently develop MDD from those who remained unaffected. DNAm-RS captured the effects of exposure to key lifestyle risk factors for MDD, revealing a potential role in risk stratification.", "URL": "https://doi.org/10.1101/19001123"} |
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] | {"Title": "Modified Long-Axis In-Plane Ultrasound Versus Short-Axis Out-of-Plane Ultrasound For Radial Arterial Cannulation: A Prospective Randomized Controlled Trial", "Authors": "Wang Jiebo, Zhang Liangcheng, Huang Qijian, Lai Zhongmeng, Wu Guohua, Lin Lei, Liu Junle, Weng Xianfeng", "Abstract": "BACKGROUND Given a low first-pass success rate of the conventional SAX (short-axis) or LAX (long-axis) approach, ultrasound-guided radial artery cannulation in adults with radial artery diameter less than 2.2 mm may be still challenging. OBJECTIVE To assess the efficacy of modified long-axis in-plane(M-LAIP) versus short-axis out-of-plane (SAOP) or conventional palpation(C-P) approaches for ultrasound-guided radial artery cannulation. DESIGN A prospective, randomized and controlled trial. SETTING Operating room in a tertiary university hospital, from 1 July 2018 to 24 November 2018. PATIENTS A total of 201 patients (age 18 to 85 years, the diameter of the radial artery less 2.2 mm) were included. Patients with history of forearm surgery, ulnar artery occlusion, abnormal Allen test, etc, were excluded from this study. INTERVENTIONS All patients were randomized 1:1:1 to M-LAIP, SAOP or C-P. MAIN OUTCOME MEASURES The primary outcome was the cannulation success rate. Secondary outcomes included first location time and cannulation time, number of attempts. RESULTS The cannulation success rate was significantly higher in the M-LAIP group than in the SAOP group or C-P group (first success rate: 80.3% vs 53.8% or 33.8%; p =0.000; total success rate: 93.9% vs 78.5% or 50.8%; p =0.000). First location time (s) was significantly longer in the M-LAIP group compared with the SAOP group (31(28-35[12-44]) vs 15(14-17[10-21]); p =0.000) and the C-P group (31(28-35[12-44]) vs 12(8-13.5 [6-37]); p =0.000). However, the time of cannulation in the M-LAIP group (29(24-45[16-313])) was significantly shorter than that in the SAOP group (45(28.5-135.5[14-346]), p =0.002) and in the C-P group(138(27-308[12-363]), p =0.000). The number of attempts decreased in the M-LAIP group compared with SAOP or C-P group (1.29\u00b10.63 vs 1.8\u00b10.89 or 2.22\u00b10.93, p =0.000). CONCLUSION The M-LAIP procedure for ultrasound-guided radial artery cannulation can offer a higher success rate of the first-attempt and total cannulation, fewer attempts and less time of cannulation. TRIAL REGISTRATION The study was registered at ClinicalTrials.gov ( http://www.chictr.org.cn/index.aspx , number: ChiCTR-IOR-17011474).", "URL": "https://doi.org/10.1101/19005496"} |
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] | {"Title": "Optimizing the deployment of ultra-low volume and indoor residual spraying for dengue outbreak response", "Authors": "Cavany Sean M., Espa\u00f1a Guido, Lloyd Alun L., Waller Lance A., Kitron Uriel, Astete Helvio, Elson William H., Vazquez-Prokopec Gonzalo M., Scott Thomas W., Morrison Amy C., Reiner Robert C. Jr., Perkins T. Alex", "Abstract": "Abstract Recent years have seen rising incidence of dengue and large outbreaks of Zika and chikungunya, which are all caused by viruses transmitted by Aedes aegypti mosquitoes. In most settings, the primary intervention against Aedes -transmitted viruses is vector control, such as indoor, ultra-low volume (ULV) spraying. Targeted indoor residual spraying (TIRS) has the potential to more effectively impact Aedes-borne diseases, but its implementation requires careful planning and evaluation. The optimal time to deploy these interventions and their relative epidemiological effects are not well understood, however. We used an agent-based model of dengue virus transmission calibrated to data from Iquitos, Peru to assess the epidemiological effects of these interventions under differing strategies for deploying them. Specifically, we compared strategies where spray application was initiated when incidence rose above a threshold based on incidence in recent years to strategies where spraying occurred at the same time(s) each year. In the absence of spraying, the model predicted 361,000 infections [inter-quartile range (IQR): 347,000 \u2013 383,000] in the period 2000-2010. The ULV strategy with the fewest median infections was spraying twice yearly, in March and October, which led to a median of 172,000 infections [IQR: 158,000 \u2013 183,000] over the 11-year study period, a 52% reduction from baseline. Compared to spraying once yearly in September, the best threshold-based strategy utilizing ULV had fewer median infections (254,000 vs. 261,000), but required more spraying (351 vs. 274 days). For TIRS, the best strategy was threshold-based, which led to the fewest infections of all strategies tested (9,900; [IQR: 8,720 \u2013 11,400], a 94% reduction), and required fewer days spraying than the equivalent ULV strategy (280). Although spraying twice each year is likely to avert the most infections, our results indicate that a threshold-based strategy can become an alternative to better balance the translation of spraying effort into impact, particularly if used with a residual insecticide. Author Summary Over half of the world\u2019s population is at risk of infection by dengue virus (DENV) from Aedes a egypti mosquitoes . While most infected people experience mild or asymptomatic infections, dengue can cause severe symptoms, such as hemorrhage, shock, and death. A vaccine against dengue exists, but it can increase the risk of severe disease in people who have not been previously infected by one of the four DENV serotypes. In many places, therefore, the best currently available way to prevent outbreaks is by controlling the mosquito population. Our study used a simulation model to explore alternative strategies for deploying insecticide in the city of Iquitos in the Peruvian Amazon. Our simulations closely matched empirical patterns from studies of dengue\u2019s ecology and epidemiology in Iquitos, such as mosquito population dynamics, human household structure, demography, human and mosquito movement, and virus transmission. Our results indicate that an insecticide that has a long-lasting, residual effect will have the biggest impact on reducing DENV transmission. For non-residual insecticides, we find that it is best to begin spraying close to the start of the dengue transmission season, as mosquito populations can rebound quickly and resume previous levels of transmission.", "URL": "https://doi.org/10.1101/19007971"} |
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] | {"Title": "HIV-associated sensory neuropathy continues to be a problem in individuals starting tenofovir-based antiretroviral treatment", "Authors": "Pillay Prinisha, Wadley Antonia L, Cherry Catherine L, Karstaedt Alan S, Kamerman Peter R", "Abstract": "Abstract HIV-associated sensory neuropathy (HIV-SN) is a common and often painful neurological condition associated with HIV-infection and its treatment. However, data on the incidence of HIV-SN in neuropathy-free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. We investigated the six-month incidence of HIV-SN in ART na\u00efve individuals initiating tenofovir (TDF)-based cART, and the clinical factors associated with the development of HIV-SN. 120 neuropathy-free and ART na\u00efve individuals initiating cART at a single centre in Johannesburg, South Africa were enrolled. Participants were screened for HIV-SN at study enrolment and then approximately every two-months for a period of approximately six-months. Symptomatic HIV-SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin-prick hypoaesthesia). Asymptomatic HIV-SN required at least two clinical signs only. A total of 88% of the cohort completed three visits within the six-month period. Eleven individuals developed asymptomatic HIV-SN and nine developed symptomatic HIV-SN, giving a six-month cumulative incidence of neuropathy of 140 cases per 1000 patients (95% CI: 80 - 210) at an incidence rate of 0.37 (95% CI: 0.2 - 0.5) per person year. Increasing height and active tuberculosis (TB) disease were independently associated with the risk of developing HIV-SN (p < 0.05). We found that within the first six months of starting cART, incident SN persists in the post-stavudine era, but may be asymptomatic.", "URL": "https://doi.org/10.1101/19002220"} |
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] | {"Title": "Knowledge about benefits and risks of undergoing cataract surgery among cataract patients in Southern China", "Authors": "Ye Guofang, Qu Bo, Shi Wen, Chen Xin, Ma Pengjuan, Zhong Yuxin, Chen Shida, Lamoureux Ecosse, Zheng Yingfeng", "Abstract": "Abstract Objective To develop a theoretical framework for assessing knowledge about the possible outcomes of undergoing cataract surgery, and explore the association of knowledge level with psychological status and decision quality among patients with cataract in Southern China. Methods The details of the knowledge scale were based on the health education information booklet provided by National Eye Institute, NIH. We used a theory-based approach to assess gist knowledge, which comprises conceptual and numeric questions related to knowledge of the possible surgical outcomes. The scale was then used in a cross-sectional study to assess the association of knowledge score with psychological status and decision quality of cataract patients, including worry, anxiety, attitudes, intentions, decisional conflict, confidence in decision making, anticipated regret and temporal orientation. Results A total of 489 participants with age-related cataract were included in this study, and 10.2% (50/489) of them had adequate level of knowledge. The knowledge scale was significantly associated to the levels of worry (Odds Ratio (OR) = 0.36, 95%CI: 0.18, 0.70; P = 0.003), anxiety (beta coefficient = -5.36, 95%CI: -8.88,-1.84; P = 0.003), inaction regret (OR = 0.49, 95%CI : 0.28, 0.88; P = 0.016) and decision conflict (beta coefficient = -7.93, 95%CI: -12.81, -3.04; P = 0.002) in multivariate analyses adjusted for age, sex, education level and literacy level. Conclusion The level of knowledge adequacy with cataract surgery outcomes is high in China and was associated with psychological status and decision quality. These findings suggest that strategies targeting knowledge of possible surgical outcomes may reduce psychological stress and improve decision quality among patients with age-related cataract.", "URL": "https://doi.org/10.1101/19014100"} |
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-0.0690813958644867,
0.8561214208602905,
-0.06153425946831703,
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0.9830852746963501,
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] | {"Title": "Characteristics of Cardiac Memory in Patients with Implanted Cardioverter Defibrillator: the CAMI study", "Authors": "Haq Kazi T., Cao Jian, Tereshchenko Larisa G.", "Abstract": "Abstract Objective The goal of this study was to determine factors associated with cardiac memory (CM) in patients with implantable cardioverter-defibrillators (ICD). Methods Patients with structural heart disease (n=20; mean age 72.6\u00b111.6 y; 80% male; mean left ventricular ejection fraction (LVEF) 31.7\u00b17.6%; history of myocardial infarction (MI) in 75%, ventricular tachycardia (VT) in 85%) and preserved atrioventricular (AV) conduction received primary (80%) or secondary (20%) prevention dual-chamber ICD. Standard 12-lead ECG was recorded in AAI and DDD mode, before and after 7 days of right ventricular (RV) pacing in DDD mode with short AV delay. Direction (azimuth and elevation) and magnitude of spatial QRS, T, and ventricular gradient (SVG) vectors were measured before and after 7 days of RV pacing. CM was quantified as the degree of alignment between QRS DDD-7 and T AAI-7 vectors (QRS DDD-7 -T AAI-7 angle). Circular statistics and mixed models with a random slope and intercept were adjusted for days 1-7 change in cardiac activation, LVEF, known risk factors, and use of medications known to affect CM. Results QRS DDD-7 -T AAI-7 angle strongly correlated (circular r = - 0.972; P<0.0001) with T AAI-7 -T DDD-7 angle. In the mixed models, history of MI (\u2212180\u00b0(95%CI \u2212320\u00b0 to \u221240\u00b0); P=0.011) and female sex (\u2212162\u00b0(95%CI \u2212268\u00b0 to \u221255\u00b0); P=0.003) counteracted CM-T azimuth changes (+132\u00b0(95%CI 80\u00b0-184\u00b0); P<0.0001). History of VT (+27(95%CI 4-46) mV*ms; P=0.007) amplified CM-T area increase (+15(95%CI 6\u201324) mV*ms; P<0.0001). Conclusions Existing cardiac remodeling affects CM in response to RV pacing. Women develop less CM than men. Activation memory is another manifestation of CM.", "URL": "https://doi.org/10.1101/19005181"} |
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] | {"Title": "Physician Suicide: A Scoping Review to Highlight Opportunities for Prevention", "Authors": "Leung Tiffany I., Pendharkar Sima S., Chen Chwen-Yuen Angie, Snyder Rebecca", "Abstract": "Abstract Objective The aim of this scoping review is to map the current landscape of published research and perspectives on physician suicide. Findings could serve as a roadmap for further investigations and potentially inform efforts to prevent physician suicide. Methods Ovid MEDLINE, PsycInfo, and Scopus were searched for English-language publications from August 21, 2017 through April 28, 2018. Inclusion criteria were a primary outcome or thesis focused on suicide (including suicide completion, attempts, and thoughts or ideation) among medical students, postgraduate trainees, or attending physicians. Opinion articles were included. Studies that were non-English, or those that only mentioned physician burnout, mental health or substance use disorders were excluded. Data extraction was performed by two authors. Results The search yielded 1,596 articles, of which 347 articles passed to the full-text review round. The oldest article was an editorial from 1903; 210 (60.3%) articles were published from 2000 to present. Authors originated from 37 countries and 143 (41.2%) were opinion articles. Most discussed were suicide risk factors and culture of practice issues, while least discussed themes included public health and postvention. Conclusions Consistency and reliability of data and information about physician suicides could be improved. Data limitations partly contribute to these issues. Also, various suicide risk factors for physicians have been explored, and several remain poorly understood. Based on this scoping review, a public health approach, including surveillance and early warning systems, investigations of sentinel cases, and postvention may be impactful next steps in preventing physician deaths by suicide.", "URL": "https://doi.org/10.1101/19004465"} |
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] | {"Title": "Maternal MTHFR A1298C polymorphism and risk of congenital heart disease in fetus", "Authors": "Rai Vandana", "Abstract": "Abstract Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, DNA synthesis and methylation. A number of studies have examined the association of maternal MTHFR A1298C polymorphism with congenital heart disease (CHD) susceptibility; however, the conclusions were contradictory. To clarify the influence of maternal MTHFR A1298C polymorphism on CHD, a meta-analysis of seventeen case- control studies was carried out. Four electronic databases - Pubmed, Google Scholars, Elsevier and Springer Link were searched upto June, 2018 for suitable articles. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to evaluate the association. Meta-analysis was performed by Mix and MetaAnalyst programs. The results of meta-analysis suggested that except co-dominant model, maternal A1298C polymorphism is risk for CHD in fetus using overall comparisons in four genetic models (C vs. A: OR= 1.19, 95% CI= 1.00-1.41, p= 0.04; CC+AC vs. AA: OR= 1.19, 95% CI= 0.97-1.4, p= 0.04; CC vs. AA: OR= 1.46, 95% CI= 1.00-2.13, p= 0.04; AC vs. AA OR= 1.13, 95% CI=0.93-1.36, p= 0.23; CC vs. AC+AA: OR=1.34, 95% CI=1.1-1.6, p=0.01). Publication bias was absent using four genetic models. In conclusion, results of present meta-analysis showed significant association between maternal MTHFR A1298C polymorphism and CHD risk.", "URL": "https://doi.org/10.1101/19010298"} |
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] | {"Title": "A Personalized Multi-Component Lifestyle Intervention Program Leads to Improved Quality of Life in Persons with Chronic Kidney Disease", "Authors": "Headley Samuel A., Hutchinson Jasmin C., Thompson Brian A., Ostroff Marissa L., Doyle-Campbell Courtney J., Cornelius Allen E., Dempsey Kristen, Siddall Jennifer, Miele Emily M., Evans Elizabeth E., Wood Brianna, Sirois Cherilyn M., Winston Brett A., Whalen Stefanie K., Germain Michael. J.", "Abstract": "Abstract Introduction Lifestyle interventions have been shown to produce favorable changes in some health outcomes in patients with chronic kidney disease (CKD). However, few such studies, employing \u201creal world\u201d methods have been completed in patients with CKD. Objective This study tested the effectiveness of a comprehensive, multicomponent, lifestyle intervention, delivered through individualized counseling on a variety of health outcomes in pre-dialysis CKD patients. Methods Eligible patients were assigned randomly to the intervention (TR) or usual care group (UC). A six-month home-based program involving personalized counseling to increase physical activity to recommended levels among stage G3a to G4 CKD patients while exchanging plant proteins for animal proteins was implemented. Physical function, cardiovascular function, dietary intake, medication use, and health-related quality of life (HRQOL) were assessed at baseline and after 1-month, 3-months (M3) and 6-months (M6). Results Forty-two, patients (age 60.2 \u00b1 9.2, BMI 34.5 \u00b1 7.8) participated in this study (TR=27 UC=15). The intervention reduced (p<0.05) brachial (bSBP) and central systolic blood pressures (cSBP) at month 3 (M3) but both were attenuated at month 6 (M6). Scores on the effect of kidney disease subscale of the HRQOL measure improved in the intervention group at M3 and M6. There was no change in the other measures of HRQOL or in any physical function scores. Conclusions This personalized multi-component lifestyle intervention enabled CKD patients to self-report fewer concerns with how CKD affected their daily lives independent of changes in physical function.", "URL": "https://doi.org/10.1101/19007989"} |
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] | {"Title": "Impact of spectrograms on the classification of wheezes and crackles in an educational setting. An interrater study", "Authors": "Aviles-Solis JC., Storvoll I, Sophie Vanbelle, Melbye H.", "Abstract": "Abstract Background Chest auscultation is a widely used method in the diagnosis of lung diseases. However, the interpretation of lung sounds is a subjective task and disagreements arise. New technological developments like the use of visual representation of sounds through spectrograms could improve the agreement when classifying lung sounds, but this is not yet known. Aims To test if the use of spectrograms improves the agreement when classifying wheezes and crackles. Methods We used 30 lung sounds recordings. The sample contained 15 normal recordings and 15 with wheezes or crackles. We produced spectrograms of the recordings. Twenty-three third to fifth-year medical students at UiT the Arctic University of Norway classified the recordings using an online questionnaire. We first showed the students examples of how wheezes and crackles looked in the spectrogram. Then, we played the recordings in a random order two times, first without the spectrogram, then with live spectrograms displayed. We asked them to classify the sounds for the presence of wheezes and crackles. We calculated kappa values for the agreement between each student and the expert classification with and without display of spectrograms and tested for significant improvement. We also calculated Fleiss kappa for the 23 observers with and without the spectrogram. Results When classifying wheezes 13/23 (1 with p<.05) students had a positive change in k, and 16/23 (2 with p<.05). All the statistically significant changes were in the direction of improved kappa values (.52 - .75). Fleiss kappa values were k=.51 and k=.56 (p=.63) for wheezes without and with spectrograms. For crackles, these values were k=.22 and k=.40 (p=<0.01) in the same order. Conclusions The use of spectrograms had a positive impact on the inter-rater agreement and the agreement with experts. We observed a higher improvement in the classification of crackles compared to wheezes.", "URL": "https://doi.org/10.1101/19005504"} |
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] | {"Title": "Out of hospital cardiac arrests in the Gulf Region: a scoping review", "Authors": "Batt Alan M., Lanos Chelsea, Delport Shannon, Al-Hasan Dalal, Knox Shane, Alhmoudi Assim, Anderson Megan, Fares Saleh, Cummins Fergal H.", "Abstract": "Abstract Background Out-of-hospital cardiac arrest (OHCA) is a major cause of mortality worldwide. Recent studies demonstrated low survival rates in Middle Eastern countries. Anecdotally there are unique demographic, cultural and logistical challenges in this region. However, there remains a paucity of data published on OHCA in the Middle East. In order to address OHCA in a meaningful manner in the region, we first need to quantify the issue. Methods We conducted a scoping review of published and grey literature on OHCA in the Gulf Cooperative Council region that utilised Arksey and O\u2019Malley\u2019s framework. Electronic databases and grey literature sources were identified and searched. Subject matter experts in the region were consulted. All types of studies in English and Arabic were included. Results A total of 24 studies were included from Saudi Arabia, the UAE, Oman, Kuwait, and Qatar. No literature was identified from the state of Bahrain. OHCA victims in the region are younger, predominantly male, and more co-morbid than other international studies. We observed low Emergency Medical Service utilisation, low bystander cardiopulmonary resuscitation, return of spontaneous circulation, and survival to discharge rates across the region. There are differences in characteristics of OHCA among ethnic groups. Discussion and conclusions We identified unique characteristics associated with OHCA in the region, variances in processes and outcomes, and a lack of coordinated effort to research and address OHCA. We recommend creating lead agencies responsible for coordinating and developing strategies such as community response, public education, and reporting databases.", "URL": "https://doi.org/10.1101/19014118"} |
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] | {"Title": "Intermittent Lactobacilli-containing Vaginal Probiotic or Metronidazole Use to Prevent Bacterial Vaginosis Recurrence: Safety and Preliminary Efficacy by Microscopy and Sequencing", "Authors": "van de Wijgert Janneke H.H.M., Verwijs Marijn C., Agaba Stephen K., Bronowski Christina, Mwambarangwe Lambert, Uwineza Mireille, Lievens Elke, Nivoliez Adrien, Ravel Jacques, Darby Alistair C.", "Abstract": "ABSTRACT Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n=17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet ( L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7-10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p=0.004), Ecologic Femi+ (3.58/person-year; p=0.043), and Gynophilus LP groups (5.36/person-year; p=0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes concentrations and/or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect microbiota or cause antimicrobial resistance.", "URL": "https://doi.org/10.1101/19001156"} |
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] | {"Title": "Systematic review and meta-analysis of the association between Epstein-Barr virus, Multiple Sclerosis, and other risk factors", "Authors": "Jacobs Benjamin M, Giovannoni Gavin, Cuzick Jack, Dobson Ruth", "Abstract": "Abstract Background EBV infection is thought to play a central role in the development of Multiple Sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk. Objective To examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk. Methods Pubmed was searched using the terms \u201cmultiple sclerosis\u201d AND \u201cEpstein Barr virus\u201d, \u201cmultiple sclerosis\u201d AND EBV, \u201cclinically isolated syndrome\u201d AND \u201cEpstein Barr virus\u201d and \u201cclinically isolated syndrome\u201d AND EBV. All abstracts were reviewed for possible inclusion. Results 262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (AP 0.48, p<1\u00d710 \u22124 ; RERI 3.84, p<5\u00d710 \u22123 ; S 1.68, p=0.06). Previous IM was associated with increased OR of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR 2.76) but not low anti-EBV antibodies (OR 1.16). No interaction between EBV and risk factors was found on a multiplicative scale. Conclusions EBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.", "URL": "https://doi.org/10.1101/19007450"} |
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] | {"Title": "Evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection", "Authors": "Trotter Alexander J., Dean Rachael, Whitehouse Celia E., Mikalsen Jarle, Hill Claire, Brunton-Sim Roxanne, Kay Gemma L., Shakokhani Majeed, Durst Alexander, Wain John, McNamara Iain, O\u2019Grady Justin", "Abstract": "Abstract Background Microbiological diagnosis of prosthetic joint infection (PJI) relies on culture techniques that are slow and insensitive. Rapid tests are urgently required to improve patient management. Calprotectin is a neutrophil biomarker of inflammation that has been demonstrated to be effective for the diagnosis of PJI. A calprotectin based lateral flow test has been developed for the rapid detection of PJI using synovial fluid samples. Methods A convenience series of 69 synovial fluid samples from patients at the Norfolk and Norwich University Hospitals (NNUH) were collected intraoperatively from 52 hip and 17 knee revision operations. Calprotectin levels were measured using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone). For all samples, synovial fluid was pipetted onto the lateral flow device and the signal was read using a mobile phone app after 15 minutes incubation at room temperature. Results According to the Musculoskeletal Infection Society (MSIS) criteria, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test against the MSIS criteria was 75%. The test had a sensitivity and specificity of 75% and 76% respectively with a positive predictive value (PPV) of 62% and a negative predictive value (NPV) of 85%. Discordant results were then reviewed by the clinical team using available patient data to develop an alternative gold standard for defining presence/absence of infection (MSIS+). Compared to MSIS+, the test showed an overall accuracy of 83%, sensitivity and specificity of 95% and 78% respectively, a PPV of 62% and an NPV of 98%. Test accuracy for hip revisions was 77% and for knee revisions was 100%. Conclusions This study demonstrates that the calprotectin lateral flow assay is an effective diagnostic test for PJI. Our data suggests that the test is likely to generate false positive results in patients with metallosis and gross osteolysis.", "URL": "https://doi.org/10.1101/19004473"} |
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] | {"Title": "An Assessment of Transparency and Reproducibility-related Research Practices in Otolaryngology", "Authors": "Johnson Austin L., Torgerson Trevor, Skinner Mason, Hamilton Tom, Tritz Daniel, Vassar Matt", "Abstract": "ABSTRACT Introduction Clinical research serves as the foundation for evidence-based patient care, and reproducibility of results is consequently critical. We sought to assess the transparency and reproducibility of research studies in otolaryngology by evaluating a random sample of publications in otolaryngology journals between 2014 and 2018. Methods We used the National Library of Medicine catalog to identify otolaryngology journals that met the inclusion criteria (available in the English language and indexed in MEDLINE). From these journals, we extracted a random sample of 300 publications using a PubMed search for records published between January 1, 2014, and December 31, 2018. Specific indicators of reproducible and transparent research practices were evaluated in a blinded, independent, and duplicate manner using a pilot-tested Google form. Results Our initial search returned 26,498 records, from which 300 were randomly selected for analysis. Of these 300 records, 286 met inclusion criteria and 14 did not. Among the empirical studies, 2% (95% CI, 0.4%-3.5%) of publications indicated that raw data were available, 0.6% (95% CI, 0.3%-1.6%) reported an analysis script, 5.3% (95% CI, 2.7%-7.8%) were linked to an accessible research protocol, and 3.9% (95% CI, 1.7%-6.1%) were preregistered. None of the publications had a clear statement claiming to replicate, or to be a replication of, another study. Conclusions Inadequate reproducibility practices exist in otolaryngology. Nearly all studies in our analysis lacked a data or material availability statement, did not link to an accessible protocol, and were not preregistered. Most studies were not available as open access. Taking steps to improve reproducibility would likely also improve patient care.", "URL": "https://doi.org/10.1101/19002238"} |
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] | {"Title": "Aggregating Multiple Real-World Data Sources using a Patient-Centered Health Data Sharing Platform: an 8-week Cohort Study among Patients Undergoing Bariatric Surgery or Catheter Ablation of Atrial Fibrillation", "Authors": "Dhruva Sanket S., Ross Joseph S., Akar Joseph G., Caldwell Brittany, Childers Karla, Chow Wing, Ciaccio Laura, Coplan Paul, Dong Jun, Dykhoff Hayley J., Johnston Stephen, Kellogg Todd, Long Cynthia, Noseworthy Peter A., Roberts Kurt, Saha Anindita, Yoo Andrew, Shah Nilay D.", "Abstract": "ABSTRACT Real-world data sources, including electronic health records (EHR) and personal digital device data, are increasingly available, but are often siloed and cannot be easily integrated for clinical, research, or regulatory purposes. We conducted a prospective cohort study of 60 patients undergoing bariatric surgery or catheter-based atrial fibrillation ablation at two U.S. tertiary care hospitals, testing the feasibility of using a patient-centered health data sharing platform to obtain and aggregate health data from multiple sources. We successfully obtained EHR data for all patients at both hospitals, as well as from 10 additional health systems, which were successfully aggregated with pharmacy data obtained for patients using CVS or Walgreens pharmacies, personal digital device data from activity monitors, digital weight scales, and single-lead ECGs, and patient-reported outcome measure data obtained through surveys to assess post-procedure recovery and disease-specific symptoms. A patient-centered health data sharing platform successfully aggregated data from multiple sources.", "URL": "https://doi.org/10.1101/19010348"} |
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] | {"Title": "Safety of Flexible Sigmoidoscopy in Pregnant Patients with known or suspected Inflammatory Bowel Disease", "Authors": "Ko Myung S., Rudrapatna Vivek A., Avila Patrick, Mahadevan Uma", "Abstract": "Abstract I. Background and Aims Lower gastrointestinal endoscopy is the gold standard for the diagnosis and staging of Inflammatory Bowel Disease (IBD). However, there is limited safety data in pregnant populations, resulting in conservative society guidelines and practice patterns favoring diagnostic delay. The aim of this study is to investigate if the performance of flexible sigmoidoscopy is associated with adverse events in pregnant patients with known or suspected IBD. II. Methods A retrospective cohort study was conducted at the University of California San Francisco (UCSF) between April 2008 and April 2019. Female patients aged between 18 and 48 years who were pregnant at the time of endoscopy were identified. All patient records were reviewed to determine disease, pregnancy course, and lifestyle factors. Two independent reviewers performed the data abstraction. Adverse events were assessed for temporal relation (defined as within 4 weeks) with endoscopy. Any discrepancies in the two reviewers\u2019 data were reviewed by a third independent investigator. Descriptive statistics of data were calculated, and comparison of continuous and categorical data were made using a one-sided Wilcoxon rank-sum test and Fisher\u2019s exact test, respectively. III. Results We report the outcomes of 48 pregnant patients across all trimesters who underwent lower endoscopy for suspected or established IBD. There were no hospitalizations or adverse obstetric events temporally associated with sigmoidoscopy. 78% of patients experienced a change in treatment following sigmoidoscopy. 12% of the patients with known IBD were found to have no endoscopic evidence of disease activity despite symptoms. IV. Conclusions Lower endoscopy in the pregnant patient with known or suspected IBD is low risk and affects therapeutic decision making. It should not be delayed in patients with appropriate indications.", "URL": "https://doi.org/10.1101/19007997"} |
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] | {"Title": "Null effect of circulating sphingomyelins on risk for breast cancer: a Mendelian randomization report using Breast Cancer Association Consortium (BCAC) data", "Authors": "Adams Charleen D.", "Abstract": "Abstract Background Changes in cellular metabolism are a hallmark of cancer and are linked with sphingolipid synthesis. Due to immense interest in how sphingolipids influence chemoresistance, more is known about the impact of sphingolipids during cancer treatment and progression than about the potential role of sphingolipids in the induction of tumors in humans. Methods Because estrogen triggers sphingolipid signaling cascades, the causal role of circulating levels of sphingomyelin (a type of sphingolipid) on breast cancer was investigated with a well-powered Mendelian randomization design. Results The results reveal a null effect (OR = 0.94; 95% CI = 0.85, 1.05; P = 0.30). Conclusion Despite the role sphingomyelins play during chemoresistance and cancer progression, circulating sphingomyelins do not appear to initiate or protect from breast cancer. Impact This finding comprises the first causal report in humans that sphingomyelins on breast cancer initiation is null. Future investigations of risk in other cancer types are needed to further explore the potential role of sphingolipid biology in cancer etiology.", "URL": "https://doi.org/10.1101/19013540"} |
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] | {"Title": "High occurrence of transportation and logistics occupations among vascular dementia patients: an observational study", "Authors": "van Loenhoud A.C., de Boer C., Wols K., Pijnenburg Y.A., Lemstra A.W., Bouwman F.H., Prins N.D., Scheltens P., Ossenkoppele R., van der Flier W.M.", "Abstract": "Abstract Background Growing evidence suggests a role of occupation in the emergence and manifestation of dementia. Occupations are often defined by complexity level, although working environments and activities differ in several other important ways. We aimed to capture the multi-faceted nature of occupation through its measurement as a qualitative (instead of a quantitative) variable and explored its relationship with different types of dementia. Methods We collected occupational information of 2,121 dementia patients with various suspected etiologies from the Amsterdam Dementia Cohort (age: 67\u00b18, 57% male, MMSE: 21\u00b15). Our final sample included individuals with Alzheimer\u2019s disease (AD) dementia (n=1,467), frontotemporal dementia (n=281), vascular dementia (n=98), Lewy Body disease (n=174) and progressive supranuclear palsy/corticobasal degeneration (n=101). Within the AD group, we used neuropsychological data to further characterize patients by clinical phenotypes. All participants were categorized into one of 11 occupational classes, across which we evaluated the distribution of dementia (sub)types with Chi 2 analyses. We gained further insight into occupation-dementia relationships through post-hoc logistic regressions that included various demographic and health characteristics as explanatory variables. Results There were significant differences in the distribution of dementia types across occupation groups (Chi 2 =85.87, p<.001). Vascular dementia was relatively common in the Transportation/Logistics sector, and higher vascular risk factors partly explained this relationship. Alzheimer\u2019s disease occurred less in Transportation/Logistics and more in Health Care/Welfare occupations, which related to a higher/lower percentage of males. We found no relationships between occupational classes and clinical phenotypes of AD (Chi 2 =53.65, n.s.). Conclusions Relationships between occupation and dementia seem to exist beyond complexity level, which offers new opportunities for disease prevention and improvement of occupational health policy.", "URL": "https://doi.org/10.1101/19005512"} |
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] | {"Title": "The epidemiology of systematic review updates: a longitudinal study of updating of Cochrane reviews, 2003 to 2018", "Authors": "Bastian Hilda, Doust Jenny, Clarke Mike, Glasziou Paul", "Abstract": "ABSTRACT Background The Cochrane Collaboration has been publishing systematic reviews in the Cochrane Database of Systematic Reviews ( CDSR ) since 1995, with the intention that these be updated periodically. Objectives To chart the long-term updating history of a cohort of Cochrane reviews and the impact on the number of included studies. Methods The status of a cohort of Cochrane reviews updated in 2003 was assessed at three time points: 2003, 2011, and 2018. We assessed their subject scope, compiled their publication history using PubMed and CDSR , and compared them to all Cochrane reviews available in 2002 and 2017/18. Results Of the 1,532 Cochrane reviews available in 2002, 11.3% were updated in 2003, with 16.6% not updated between 2003 and 2011. The reviews updated in 2003 were not markedly different to other reviews available in 2002, but more were retracted or declared stable by 2011 (13.3% versus 6.3%). The 2003 update led to a major change of the conclusions of 2.8% of updated reviews (n = 177). The cohort had a median time since publication of the first full version of the review of 18 years and a median of three updates by 2018 (range 1\u201311). The median time to update was three years (range 0\u201314 years). By the end of 2018, the median time since the last update was seven years (range 0\u201315). The median number of included studies rose from eight in the version of the review before the 2003 update, to 10 in that update and 14 in 2018 (range 0\u2013347). Conclusions Most Cochrane reviews get updated, however they are becoming more out-of-date over time. Updates have resulted in an overall rise in the number of included studies, although they only rarely lead to major changes in conclusion.", "URL": "https://doi.org/10.1101/19014134"} |
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] | {"Title": "Isolated night cough in children: how does it differ from wheeze?", "Authors": "Jurca Maja, Goutaki Myrofora, Latzin Philipp, Gaillard Erol A., Spycher Ben D., Kuehni Claudia E.", "Abstract": "Abstract Background Children with night cough but no wheeze might have a mild form of asthma (cough variant asthma), sharing risk factors with children who wheeze, and possibly developing wheeze later. Methods We compared risk factors of children with isolated night cough and children with wheeze in the Leicester Respiratory Cohort study at ages 1, 4, 6, and 9 years. We also compared prognoses of children with isolated night cough, children with wheeze, and asymptomatic children. Results Among 4,101 children at age 1 year, 2,854 at 4, 2,369 at 6, and 1,688 at 9 years, the prevalence of isolated night cough was 10% at age 1 and 18% in older children, while prevalence of wheeze decreased from 35% at 1 year to 13% at age 9. Although many risk factors were the same for cough and wheeze, day care, reflux, and family history of bronchitis were more strongly associated with cough, and male sex and family history of asthma with wheeze. Over one-third of pre-schoolers with cough continued to cough at school age, but their risk of developing wheeze was similar to that of children asymptomatic at earlier surveys. Wheeze tracked more strongly throughout childhood than cough. Conclusions Some risk factors for cough and wheeze were shared and some were not; there was little evidence that children with isolated night cough have an increased risk of future wheeze. This suggests that only a fraction of children with isolated night cough might have a variant of asthma, if at all.", "URL": "https://doi.org/10.1101/19007500"} |
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] | {"Title": "Rationalising neurosurgical head injury referrals: The development and implementation of the Liverpool Head Injury Tomography Score (Liverpool HITS) for mild traumatic brain injury", "Authors": "Gillespie Conor SN, Mcleavy Christopher M, Islim Abdurrahman I, Prescott Sarah, McMahon Catherine J", "Abstract": "Abstract Objectives To develop and implement a radiological scoring system to define a \u2018surgically significant\u2019 mild Traumatic Brain Injury (TBI), stratify neurosurgical referrals and improve communication between referral centres and neurosurgical units. Design Retrospective single centre case-control analysis of ten continuous months of mild TBI referrals. Setting A major tertiary neurosurgery centre in England, UK. Participants All neurosurgical referrals with a mild TBI (GCS 13-15) during the period of 1 st January to 30 th October 2017 were eligible for the study. 1248 patients were identified during the study period, with 1144 being included in the final analysis. Interventions All patients\u2019 CT head results from the referring centres were scored retrospectively using the scoring system and stratified according to their mean score, and if they were accepted for transfer to the neurosurgical centre or managed locally. Main outcome measure Determine the discriminatory and diagnostic power, sensitivity and specificity of the scoring system for predicting a \u2018surgically significant\u2019 mild TBI. Results Most patients referred were male (59.4%, N=681), with a mean age of 69 years (SD=21.1). Of the referrals to the neurosurgical centre, 17% (n=195) were accepted for transfer and 83% (n=946) were not accepted. The scoring system was 99% sensitive and 51.9% specific for determining a surgically significant TBI. Diagnostic power of the model was fair with an area under the curve of 0.79 (95% CI 0.76 to 0.82). The score identified 495 (52.2%) patients in ten months of referrals that could have been successfully managed locally without neurosurgical referral if the scoring system was correctly used at the time of injury. Conclusion The Liverpool Head Injury Tomography Score (HITS) score is a CT based scoring system that can be used to define a surgically significant mild TBI. The scoring system can be easily used by multiple healthcare professionals, has high sensitivity, will reduce neurosurgical referrals, and could be incorporated into local, regional and national head injury guidance.", "URL": "https://doi.org/10.1101/19004499"} |
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] | {"Title": "Gait differences in patients with multiple sclerosis who have low and high levels of disability", "Authors": "Fraser John J., Stephenson Jeannie B.", "Abstract": "Abstract Background Multiple Sclerosis (MS) often results in gait impairment and disability. Objective To investigate differences in spatiotemporal gait characteristics of people with MS who have low versus high levels of disability. Between trial and inter-limb consistency and the association of gait variables with level of disability were also investigated. Methods Participants with MS who had either low-disability [n=7; 3 females; EDSS mean: 2.7\u00b10.5, range 2.0-4.5; BMI=26.9\u00b16.6] or high-disability [n=11; 6 females; EDSS mean: 2.7\u00b10.5, range 6.0-6.5; BMI=27.8\u00b11.5) performed 2 trials of self-selected walking on an instrumented walkway. Differences in group, limb, and group by limb interactions were assessed using analysis of variance, independent-measures t-tests, and Cohen\u2019s d effect sizes (ES). Between-trial consistency of gait were assessed with intra-class correlation coefficients (2, k). Results Participants in the high disability group had increased step time (ES=0.8), cycle time (ES=0.8), and ambulation time (ES=1.2) while taking shorter strides (ES=0.9) and more steps at a slower rate (ES=1.1). The high disability group demonstrated less between-trial consistency for 69% of gait variables when compared to the low disability group. Conclusion People with MS who have high levels of disability walk differently and with less consistency than those with lower levels of disability.", "URL": "https://doi.org/10.1101/19000166"} |
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] | {"Title": "Can the impact of childhood adiposity on disease risk be reversed? A Mendelian randomization study", "Authors": "Richardson Tom G., Sanderson Eleanor, Elsworth Benjamin, Tilling Kate, Davey Smith George", "Abstract": "Abstract Objective To evaluate whether early life adiposity has an independent effect on later life disease risk or whether its influence is mediated by adulthood body mass index (BMI). Design Two-sample univariable and multivariable Mendelian randomization. Setting The UK Biobank (UKB) prospective cohort study and four large-scale genome-wide association study (GWAS) consortia. Participants 453,169 participants enrolled in the UKB and a combined total of over 700,000 individuals from different GWAS consortia. Exposures Measured BMI during adulthood (mean age: 56.5) and self-reported adiposity at age 10. Main outcome measures Coronary artery disease (CAD), type 2 diabetes (T2D), breast cancer and prostate cancer. Results Individuals with genetically predicted higher BMI in early life had increased odds of CAD (OR:1.49, 95% CI:1.33-1.68) and T2D (OR:2.32, 95% CI:1.76-3.05) based on univariable MR (UVMR) analyses. However, there was little evidence of a direct effect (i.e. not via adult BMI) based on multivariable MR (MVMR) estimates (CAD OR:1.02, 95% CI:0.86-1.22, T2D OR:1.16, 95% CI:0.74-1.82). In the MVMR analysis of breast cancer risk, there was strong evidence of a protective direct effect for early BMI (OR:0.59, 95% CI:0.50-0.71), although adult BMI did not appear to have a direct effect on this outcome (OR:1.08, 95% CI:0.93-1.27). Adding age of menarche as an additional exposure provided weak evidence of a total causal effect (UVMR OR:0.98, 95% CI:0.91-1.06) but strong evidence of a direct causal effect, independent of early and adult BMI (MVMR OR:0.90, 95% CI:0.85-0.95). Weak evidence of a causal effect was observed in the MVMR analysis of prostate cancer (early life BMI OR:1.06, 95% CI:0.81-1.40, adult BMI OR:0.87, 95% CI:0.70-1.08). Conclusions Our findings suggest that increased CAD and T2D risk attributed to early life adiposity can be mitigated if individuals reduce their weight in later life. However, having a low BMI during childhood may increase risk of breast cancer regardless of changes to weight in later life, with timing of puberty also putatively playing an important role.", "URL": "https://doi.org/10.1101/19008011"} |
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] | {"Title": "Pre-diagnostic loss to follow-up in an active case-finding TB program: a mixed-methods study from rural Bihar, India", "Authors": "Garg Tushar, Gupta Vivek, Sen Dyuti, Verma Madhur, Brouwer Miranda, Mishra Rajeshwar, Bhardwaj Manish", "Abstract": "ABSTRACT background Despite active case-finding (ACF) identifying more presumptive and confirmed TB cases, high pre-diagnostic loss to follow-up (PDLFU) among presumptive TB cases referred for diagnostic test remains a concern. We aimed to quantify the PDLFU, and identify the barriers and enablers in undergoing a diagnostic evaluation in an ACF program implemented in 1.02 million rural population in the Samastipur district of Bihar, India. methods During their routine work, Accredited Social Health Activists (ASHA, a community health worker or CHW), informal providers, and community laypersons identified people at risk of TB, and referred them to the program. A field coordinator (FC) screened them for TB symptoms at the patient\u2019s home. The identified presumptive TB cases were accompanied by the CHW to a designated government facility for diagnostics. Those with a confirmed TB diagnosis were put on treatment by the CHW and followed-up till treatment completion. All services were provided free of cost and patients were supported throughout the care pathway, including a transport allowance. We analyzed programmatically collected data, conducted in-depth interviews with patients, and focus group discussions with the CHWs and FCs in an explanatory mixed-methods design. results A total of 11146 presumptive TB cases were identified from January 2018 to December 2018, out of which 4912 (44.1%) underwent a diagnostic evaluation. The key enablers were CHW accompaniment and support in addition to the free TB services in the public sector. The major barriers identified were transport challenges, deficient family and health provider support, and poor services in the public system. conclusion If we are to find missing cases, the health system needs urgent reform, and diagnostic services need to be patient-centric. A strong patient support system engaging all stakeholders and involvement of CHWs in routine TB care is an effective solution. STRENGTHS AND LIMITATIONS OF THIS STUDY First such study to explore the reasons for pre-diagnostic loss to follow-up A mixed-method design including the views of both patients and community health workers Uses operational data from a routine programmatic setting at an NGO site No record of the actual number of people screened intuitively before being referred to the program. No record of patients accessing diagnostics in private sector and those completing the diagnostic process.", "URL": "https://doi.org/10.1101/19005199"} |
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] | {"Title": "Rate of Force Development is Related to Maximal Force, Muscle Quality and Physical Function in Patients With Chronic Kidney Disease Predialysis", "Authors": "Gollie Jared M., Harris-Love Michael O., Patel Samir S., Blackman Marc R.", "Abstract": "ABSTRACT Background Physical function is severely compromised in people with chronic kidney disease (CKD) and worsens with continued decreases in kidney function. Neuromuscular force capacity is a key determinant of physical function in healthy older adults, though its importance in persons with CKD is less understood. Methods This study aimed to determine the relationships among rate of force development (RFD), muscle quality and physical function in a group of community-dwelling, middle-aged and older men (n=14; age=71.2\u00b16.2 years) with CKD stages 3 and 4 (eGFR=37.5\u00b110.4 ml/min per 1.73 m 2 ). Force characteristics were determined from maximal knee extensor isometric contractions and muscle quality was estimated using ultrasound grayscale analysis. Physical function was assessed by the Short Physical Performance Battery (SPPB) and 5-repetition sit-to-stand (STS) test. Results eGFR was directly related to SPPB (r=0.54, p=0.044) and inversely related to STS (r=-0.62, p=0.029). RFD was positively related to SPPB at time points 0-50 ms, 50-100 ms, and 0-300 ms (RFD 0-50 , r=0.73, p=0.010; RFD 50-100 , r=0.67, p=0.022 and RFD 0-300 r=0.61, p=0.045); and inversely related to STS at time points 0-50 ms, 50-100 ms, and 0-300 ms (RFD 0-50 , r=-0.78, p=0.007; RFD 50-100 , r=-0.78, p=0.006 and RFD 0-300 r=-0.76, p=0.009), respectively. RFD was positively associated with maximal voluntary force (MVF) at times 50-100 ms, 100-200 ms, and 0-300 ms (RFD 50-100 , r=0.72, p=0.011; RFD 100-200 , r=0.66, p=0.025; and RFD 0-300 r=0.70, p=0.016), respectively. Neither MVF nor muscle quality was significantly associated with functional measures. Conclusions RFD is an important determinant of physical function in middle-aged and older men with CKD stages 3 and 4.", "URL": "https://doi.org/10.1101/19013557"} |
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] | {"Title": "Quaternary Prevention: Is this Concept Relevant to Public Health? A Bibliometric and Descriptive Content Analysis", "Authors": "Depallens Miguel Andino, Guimar\u00e3es Jane Mary de Medeiros, Filho Naomar Almeida", "Abstract": "Abstract Objective To measure and map research output on Quaternary Prevention (P4) and outline research trends; to assess the papers content, mainly regarding methods and subjects approached in order to contribute to the improvement of global knowledge about P4 and to evaluate its relevance for public health. Design Bibliometric and descriptive content analysis. Articles reviewed Scientific articles about P4 recorded in Pubmed, LILACS, Scielo or CINAHL published until August 2018, with correspondent full articles available in Portuguese, English, Spanish, German or French. Main outcome measures Year of publication, first authors\u2019 name and nationality, journals\u2019 name, country and ranking, publication language, used methods and main reported subjects. Results 65 articles were included, published in 33 journals of 16 countries between 2003 and 2018 with a peak of publications in 2015. The first authors came from 17 different countries, 23% of them were Brazilian and Uruguay was the leading nation according to the scientific production per capita. 40% of all the selected articles were in English, 32% in Portuguese, 26% in Spanish. 28% of the papers were published in Q1 or Q2 journals. The research outputs on P4 begun first in the South of Europe, went to South America and then expanded worldwide. 88% of the articles were bibliographic research and 38% of all focused on specific examples of medical overuse (including several screening tests). Conclusions Quaternary prevention represents an ethical and valid approach to prevent occurence of iatrogenic events and to achieve equal and fair access to health services. Conceptual, geographical and linguistic elements, as well as WONCA conferences and type of healthcare systems in the authors\u2019 country were fundamental factors that affected research output. The quality and quantity of available studies is still limited, therefore further investigations are recommended to assess the effective impact of P4 on public health.", "URL": "https://doi.org/10.1101/19007526"} |
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] | {"Title": "Tensor Fasciae Suralis \u2013 Prevalence Study and Literature Review", "Authors": "Bale Logan S., Herrin Sean O.", "Abstract": "SUMMARY Tensor fasciae suralis (TFS) is an accessory muscle of the posterior lower extremity. Although TFS has been documented in cadaveric and radiological reports, its prevalence remains unknown. The TFS variant is noteworthy to anatomists, as it may be encountered in the dissection laboratory, and clinicians, as the muscle could potentially cause confusion during physical examination or diagnostic imaging. Multiple variations of TFS have been reported in the literature, suggesting the need for a classification system. We dissected 236 formalin-fixed cadaveric lower limbs to determine the prevalence of TFS. The PubMed and MEDLINE databases were searched to compare the anatomical features of independent TFS case reports. In our prevalence study, the TFS muscle was identified in three lower limbs (1.3%). In total, 35 cases of TFS (31 cadaveric and four radiological) were identified in the literature. Our literature review revealed that the accessory muscle most often arises as a single head from the long head of the biceps femoris, yet many other presentations have been documented. The need for a classification system to distinguish between the subtypes of TFS became apparent during the literature review. Tensor fasciae suralis is a rare muscle, present in only 3 of 236 (1.3%) cadaveric lower limbs dissected in this study. We propose the use of a classification system, based on muscle origin and number of heads, to better organize the subtypes of TFS.", "URL": "https://doi.org/10.1101/19010389"} |
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] | {"Title": "Novel prefrontal synthesis intervention improves language in children with autism", "Authors": "Vyshedskiy Andrey, Khokhlovich Edward, Dunn Rita, Faisman Alexander, Elgart Jonah, Lokshina Lisa, Gankin Yuriy, Ostrovsky Simone, deTorres Lauren, Edelson Stephen M, Ilyinskii Petr O", "Abstract": "Abstract Prefrontal synthesis (PFS) is defined as the ability to juxtapose mental objects at will. Paralysis of PFS may be responsible for the lack of comprehension of spatial prepositions, semantically-reversible sentences, and recursive sentences observed in 30 to 40% of individuals with ASD. In this report we present data from a three-year-long clinical trial of 6,454 ASD children aged 2-12 years, which were administered a PFS-targeting intervention. Tablet-based verbal and nonverbal exercises emphasizing mental-juxtaposition-of-objects were organized into an application called Mental Imagery Therapy for Autism (MITA). The test group included participants who completed more than one thousand exercises and made no more than one error per exercise. The control group included the rest of participants. The test group participants were matched to the control group by age, gender, expressive language, receptive language, sociability, cognitive awareness, and health at the 1 st evaluation. The test group showed 1.7-fold improvement in receptive language score vs. control group (p=0.0002) and 1.4-fold improvement in expressive language (p=0.0144). No statistically significant change was detected in other subscales not targeted by the exercises. These findings show that language acquisition improves by training PFS and warrants further investigation of the PFS-targeting intervention in a randomized controlled study.", "URL": "https://doi.org/10.1101/2019.12.10.19014159"} |
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] | {"Title": "Community gender systems and daughter\u2019s risk of female genital mutilation/cutting: New theory and application to Egypt", "Authors": "Yount Kathryn M., Cheong Yuk Fai, James-Hawkins Laurie, Grose Rose Grace, Hayford Sarah R.", "Abstract": "Abstract We proposed and tested a feminist social-ecological theory about daughters\u2019 experience of female genital mutilation/cutting (FGMC) in Egypt, where over 90% of women ages 15\u201349 are cut. FGMC has potential adverse effects on demographic and health outcomes and has been defined as a human-rights violation. Contextual factors are important determinants of FGMC, but an integrated theory is lacking, and quantitative multilevel research is limited. We theorized that more favorable community-level gender systems, including gender norms opposing FGMC and expanded opportunities for women outside of the family, would be associated with a daughter\u2019s lower risk of FGMC and would strengthen the negative association of a mother\u2019s opposition to FGMC with her daughter\u2019s risk of cutting. Using a national sample of 14,171 mother-daughter dyads from the 2014 Egypt Demographic and Health Survey, we estimated multilevel discrete-time hazard models to test these relationships. Community gender norms opposing FGMC had significant direct, negative associations with the hazard that a daughter was cut, but women\u2019s opportunities outside the family did not. Maternal opposition to FGMC was negatively associated with cutting a daughter, and these associations were stronger where community opposition to FGMC and opportunities for women were greater. Results provided good support for a gender-systems theory of the multilevel influences on FGMC. Integrated, multilevel interventions that address gender norms about FGMC and opportunities for women in the community, as well as beliefs about the practice among the mothers of at-risk daughters may be needed for sustainable declines in the practice.", "URL": "https://doi.org/10.1101/19005520"} |
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] | {"Title": "The ansa subthalamica: a neglected fiber tract", "Authors": "Lopes Alho Eduardo Joaquim, Di Lorenzo Alho Ana Tereza, Horn Andreas, M. Martin Maria da Graca, Edlow Brian L, Fischl Bruce, Nagy J\u00f3zsef, Fonoff Erich T, Hamani Clement, Heinsen Helmut", "Abstract": "Abstract Background The pallidofugal pathways are classically subdivided into ansa lenticularis, lenticular fasciculus, and subthalamic fasciculus. In addition to these three subsystems, we characterize an anatomical structure that connects the antero-medial pole of the subthalamic nucleus to the ventral portions of the pallidum, both related to limbic processing of information. This bundle has been previously considered to form a part of the ansa lenticularis, however, it shows striking differences on histology and MRI features compared to the ansa lenticularis, and therefore we suggest to denominate it ansa subthalamica . Objectives To describe the ansa subthalamica as a different structure than the ansa lenticularis, that can be recognized by different methods (histology, high-field MRI and connectome tractography), including current 3T clinical imaging. Methods A complete human brain was histologically processed and submitted to registration procedures to correct for tissue deformations and normalization to MNI space. Coordinates of histological structures were then comparable to high-field (7T) post-mortem and in vivo MRIs, 13 pre-operative 3T imaging of parkinsonian patients and normative connectome tractography. Mean intensity gray values for different structures were measured in Susceptibility-Weighted Images. Results It was possible to characterize this structure with different methods and there was significant difference in signal intensity in the ansa subthalamica (hypointense), compared to the ansa lenticularis (hyperintense). Conclusions The ansa subhtalamica may represent the anatomical pathway that connects limbic regions of the STN and pallidum, and should be investigated as a possible substrate for limbic effects of stereotactic surgery of the subthalamic region.", "URL": "https://doi.org/10.1101/19002352"} |
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] | {"Title": "The prevalence of scabies, pyoderma and other communicable dermatoses in the Bijagos Archipelago, Guinea-Bissau", "Authors": "Marks Michael, Sammut Thomas, Cabral Marito Gomes, da Silva Eunice Teixeira, Goncalves Adriana, Rodrigues Amabelia, Mandjuba Crist\u00f3v\u00e3o, Nakutum Jose, Ca Janete, D\u2019Alessandro Umberto, Achan Jane, Logan James, Bailey Robin, Mabey David, Last Anna, Walker Stephen L.", "Abstract": "Abstract Background Skin diseases represent a significant public health problem in most low and middle income settings. Nevertheless, there is a relative paucity of high-quality epidemiological data on the prevalence of these conditions. Materials/methods We conducted two cross-sectional population-based skin-surveys of children (6 months to 9 years old) in the Bijag\u00f3s Archipelago of Guinea-Bissau during the dry season (February-March 2018) and the wet season (June-July 2018). Following a period of training, a nurse performed a standardised examination for communicable dermatoses for each participant. We calculated the prevalence of each skin condition and investigated demographic associations. Results 1062 children were enrolled in the dry season survey of whom 318 (29.9%) had at least one skin diseases. The most common diagnosis was tinea capitis (154/1062, 14.5% - 95% CI 12.5-16.8%) followed by tinea corporis (84/1062, 7.9% - 95% CI 6.4-9.7%), pyoderma (82/1062, 7.7% - 95% CI 6.2-9.5%) and scabies (56/1062. 5.2% - 95%CI 4.0 \u2013 6.8%). 320 children were enrolled in the wet season survey of whom 121 (37.8%) had at least one skin problem. Tinea capitis remained the most common diagnosis (79/320, 24.7% - 95% CI 20.1 \u2013 29.9%), followed by pyoderma (38/320, 11.9% - 95% CI 8.6-16.1%), tinea corporis (23/320, 7.2% - 95% 4.7 \u2013 10.7%) and scabies (6/320, 1.9% - 95% CI 0.8-4.2%). Conclusions Our study, which utilised robust population-based cluster random sampling methodology, demonstrates the substantial disease burden caused by common communicable dermatoses in this setting. Given these findings, there is a need to consider common dermatoses as part of Universal Health Coverage to deliver \u2018skin-health for all\u2019. Author Summary Skin conditions are very common in many low and middle income settings but there have been relatively few surveys of skin disease conducted using the best epidemiological approaches. We performed two cross-sectional population-based skin-surveys of children in the Bijag\u00f3s Archipelago, Guinea-Bissau, using gold-standard sampling methodologies. Skin conditions were extremely common and almost 30% of children had at least one common, infectious skin condition in both surveys. Fungal skin and scalp infections were the most common conditions followed by bacterial skin infections. Our survey demonstrates that common, easily treatable skin conditions are responsible for a high burden of disease in this population. Skin-health should be considered a key component of the Universal Health Coverage agenda.", "URL": "https://doi.org/10.1101/19000257"} |
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] | {"Title": "Potential impact of outpatient stewardship interventions on antibiotic exposures of bacterial pathogens", "Authors": "Tedijanto Christine, Grad Yonatan H, Lipsitch Marc", "Abstract": "Abstract The relationship between antibiotic stewardship and population levels of antibiotic resistance remains unclear. In order to better understand shifts in selective pressure due to stewardship, we use publicly available data to estimate the effect of changes in prescribing on exposures to frequently used antibiotics experienced by potentially pathogenic bacteria that are asymptomatically colonizing the microbiome. We quantify this impact under four hypothetical stewardship strategies. In one scenario, we estimate that elimination of all unnecessary outpatient antibiotic use could avert 6 to 48% (IQR: 17 to 31%) of exposures across pairwise combinations of sixteen common antibiotics and nine bacterial pathogens. All scenarios demonstrate that stewardship interventions, facilitated by changes in clinician behavior and improved diagnostics, have the opportunity to broadly reduce antibiotic exposures across a range of potential pathogens. Concurrent approaches, such as vaccines aiming to reduce infection incidence, are needed to further decrease exposures occurring in \u201cnecessary\u201d contexts.", "URL": "https://doi.org/10.1101/19008029"} |
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] | {"Title": "The Impact of Pre-exposure Prophylaxis for Human Immunodeficiency Virus on Gonorrhea Prevalence", "Authors": "Pharaon Joe, Bauch Chris T.", "Abstract": "Abstract Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in reducing the risk of HIV infection in gay and bisexual men who have sex with men (GbMSM). However, PrEP does not protect against other sexually transmitted infections (STIs). In some populations, PrEP has also led to riskier behaviour such as reduced condom usage, with the result that the prevalence of bacterial STIs like gonorrhea has increased. Here we develop a compartmental model of the transmission of HIV and gonorrhea, and the impacts of PrEP, condom usage, STI testing frequency and potential changes in sexual risk behaviour stemming from the introduction of PrEP in a population of GbMSM. We find that introducing PrEP causes an increase in gonorrhea prevalence for a wide range of parameter values, including at the current recommended frequency of STI testing once every 3 months for individuals on PrEP. Moreover, the model predicts that a higher STI testing frequency alone is not enough to prevent a rise in gonorrhea prevalence, unless the testing frequency is increased to impractical levels. However, testing every 2 months in combination with sufficiently high condom usage by individuals on PrEP would be successful in maintaining gonorrhea prevalence at pre-PrEP levels. The results emphasize that programs making PrEP more available should be accompanied by efforts to support condom usage and frequent STI testing, in order to avoid an increase in the prevalence of gonorrhea and other bacterial STIs.", "URL": "https://doi.org/10.1101/19005207"} |
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] | {"Title": "Reactions to an Online Demonstration of the Effect of Increased Fruit and Vegetable Consumption on Appearance: Survey", "Authors": "Cairns Patrick, Ozakinci Gozde, Perrett David Ian", "Abstract": "Abstract Background Inadequate fruit and vegetable consumption causes a considerable disease burden and premature mortality. Despite considerable public health promotion of a healthy diet the average consumption is still below recommended levels. Fruit and vegetable consumption influences human skin colour, increasing red/yellow/orange pigment in the skin. Given that this colour is deemed attractive and healthy-looking, the appearance benefit may provide motivation to eat more fruit and vegetables. Such appearance motivation could be particularly effective in young individuals who currently eat least fruit and vegetables. Objectives To assess how widely the impact of diet on skin colour is known within the UK. To compare the strength of motivation to eat fruit and vegetables based on health and appearance benefits and to compare the effect of different UK demographics on motivation. Methods Four groups of UK residents (N = 200 each group) were recruited through the Prolific online platform. Groups comprised younger (aged 18-24) and older adults (aged 40-60) of low and high self-reported socioeconomic status (1-5 and 6-10 on a 10-point rating scale). Facial images simulating the skin colour associated with low and high fruit and vegetable diets were shown to participants. Questionnaires were used to assess (1) background knowledge of the health and skin colour effects of dietary fruit and vegetables; (2) the specific motivational impact of the skin colour illustration and (3) the relative importance of motivation to consume fruit and vegetables arising from health and skin colour appearance benefits. Results (1) 61% of all participants were unaware of the dietary\u2013skin colour association. (2) 57% of participants found the simple demonstration of the dietary impact on skin colour positively motivating to eat more fruit and vegetables. The visual demonstration was equally motivating for participants of high and low self-reported socioeconomic status ( P = .63) and different ethnic backgrounds (White N = 453, Black N = 182, Asian N = 87, P = .22). Health benefits from a diet high in fruit and vegetables were regarded as more motivating than skin colour appearance benefits. The appearance benefits of a high fruit and vegetable diet (compared to the health benefits) were relatively more important for the younger participants (Mann-Whitney U = 96,263, P < .001) and for women (N = 489) than for men (N = 310, U = 83,763, P = .01). Conclusions These findings indicate that promotion of the skin colour effects of diets high in fruit and vegetables could provide additional motivation for a healthier diet. Our study indicates the wide appeal of appearance benefits from dietary fruit and vegetable (across ethnicity and socioeconomic status) and particularly amongst young adults where inadequate diet is most prevalent.", "URL": "https://doi.org/10.1101/19004523"} |
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] | {"Title": "Classifying post-traumatic stress disorder using the magnetoencephalographic connectome and machine learning", "Authors": "Zhang Jing, Richardson J. Don, Dunkley Benjamin T.", "Abstract": "Abstract Given the subjective nature of conventional diagnostic methods for post-traumatic stress disorder (PTSD), an objectively measurable biomarker is highly desirable. Macroscopic neural circuits measured using magnetoencephalography (MEG) has previously been shown to be indicative of the PTSD phenotype and severity. In the present study, we employed a machine learning-based classification framework using MEG neural synchrony to distinguish combat-related PTSD from trauma-exposed controls. Support vector machine (SVM) was used as the core classification algorithm. A recursive random forest feature selection step was directly incorporated in the nested SVM cross validation process (CV-SVM-rRF-FS) for identifying the most important features for PTSD classification. For the five frequency bands tested, the nested CV-SVM-rRF-FS analysis selected the minimum numbers of edges per frequency that could serve as a PTSD signature and be used as the basis for SVM modelling. Many of the selected edges have been reported previously to be core in PTSD pathophysiology, with frequency-specific patterns also observed. Furthermore, the independent partial least squares discriminant analysis suggested low bias in the nested CV-SVM-rRF-FS process. The final SVM models built with selected features showed excellent PTSD classification performance (area-under-curve value up to 0.9). Testament to its robustness when distinguishing individuals from a heavily-traumatised control group, these developments for a classification model for PTSD also provide a comprehensive machine learning-based computational framework for classifying other mental health challenges using MEG connectome profiles.", "URL": "https://doi.org/10.1101/19008037"} |
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] | {"Title": "Rate and predictors of Treatment Failure among pediatric population taking Highly Active Antiretroviral Therapy in Ethiopia", "Authors": "Getaneh Yimam, Yizengaw Ajanaw, Likie Agajie, Getahun Mulusew, Feleke Altaye, Kidane Eleni, Yilma Amelework, Mulugeta Achamyeleh, Moshago Tezera, Assefa Yibeltal", "Abstract": "Abstract Background Though the unprecedented global effort at scaling up universal access to antiretroviral therapy (ART) has decreased the progression of HIV, treatment failure (TF) among pediatric patients receiving ART against human immunodeficiency virus (HIV) is becoming a global public health concern which may impact on treatment outcome. Thus, the aim of this study was to determine the rate and predictors of treatment failure (TF) among HIV-infected pediatric patients taking ART in Ethiopia. Methods A prospective and retrospective follow-up study was conducted from March 2016 to 2017. Retrospective clinical and laboratory data were captured from patients\u2019 medical record. Socio-demographics and explanatory variables of participants were collected using pre-tested structured questionnaire and study participants were followed for three to six month after baseline viral load has been done to classify virologic failure (VF). TF was ascertained from population who virally failed with the denominator of population taking ART. Chi-square test and multiple logistic regressions were conducted to assess predictors TF. Statistical significance was set at P-value less than 0.05. Results A total of 554 pediatrics patients taking ART from 40 selected health facilities were included in the study. Viral load suppression (VLS) (VL<1000 copies/ml) among pediatric population taking ART in Ethiopia were found to be 344 (62.1%). From those who was not virally suppressed at baseline of the study 210 (37.9%), 99 (51.6%) were re-suppressed after three to six month of enhanced adherence and counseling, leading the overall virologic failure (VF) among pediatric population taking ART in Ethiopia to be 93 (17.3%). The mean CD4 count was improved from 490 cells/ml at ART initiation to 921 cells/ml after 80 months of ART exposure. Moreover, the clinical outcome was improved from 42% to 89% at ART initiation and after 80 month of ART experience. CD4 count, clinical stage, Hemoglobin and weight were found to be predictors of VF. Moreover; family HIV and disclosure status, duration on ART, age, being orphan, stigma and medication adherence have significant association with VF. Conclusions The low level of VLS (62.1%) and the high level of VF (18.3%) could explain the challenge on the national ART program among pediatric population. The significant improvement on immunologic and clinical outcome could indicate the success of ART on treatment outcome among pediatric population. CD4 count, clinical stage, Hemoglobin and weight could be good predictors of TF among pediatric population. Improving disclosure status, stigma and medication adherence could improve the treatment outcome of pediatric population taking ART in Ethiopia.", "URL": "https://doi.org/10.1101/19005538"} |
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] | {"Title": "Association of Single Nucleotide Polymorphisms with Dyslipidemia in Antiretroviral Exposed HIV Patients: A Case-Control Study in a Ghanaian population", "Authors": "Obirikorang Christian, Acheampong Emmanuel, Quaye Lawrence, Yorke Joseph, Amos-Abanyie Ernestine Kubi, Akyaw Priscilla Abena, Anto Enoch Odame, Bani Simon Bannison, Asamoah Evans Adu, Batu Emmanuella Nsenbah", "Abstract": "Abstract Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia HIV patients on ART in Ghana have not been fully explored. A total of 289 HIV-infected patients on stable ART for at least a year and 104 age-matched controls with no history of HIV and dyslipidemia were recruited for the study. Fasting blood was collected into EDTA for lipids measurements. Lipid profiles were determined as a measure of dyslipidemia. There was a significant difference in case-control prevalence for dyslipidemia (31.4% vs. 18.3%, p=0.013). Four candidate Single Nucleotide Polymorphisms (SNPs) from four genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex Ligation Detection Reaction (LDR). Significantly increased levels of total cholesterol (TC) low-density lipoprotein cholesterol (LDL-C) and triglycerides [TG] were observed in protease inhibitor-based (PI) treated case subjects compared to non-PI-based case subjects. The population frequency of homozygotes for the rare alleles rs6511720 (T/T), rs2066714 (G/G), rs10892151 (T/T) and rs662799 (G/G) were 3.6%, 9.6%, 6.4% and 6.0%, respectively. Adjusted analysis controlling for age, gender and duration of treatment revealed that rare homozygous genotypes for APOA5 (G/G) [aOR=18.74(5.65-54.73), p<0.0001], ABCA1 (G/G) [aOR=3.94(0.86 \u221217.38), p=0.033] and DSCAML1 (T/T) [aOR=11.46(3.651-43.56), p<0.0001) were significant factors for high TC. Subjects with the T/T genotype for DSCAML1 (rs10892151) were associated with a high likelihood of raised levels of LDL-C [aOR=3.76(1.43-8.46), p=0.033]. Furthermore, the rare homozygous genotype for ABCA1 (G/G) [aOR=5.67(3.43-13.54), p<0.0001] and LDLR (T/T) [aOR=4.46(1.86-10.56), p<0.0001) was significantly associated with hypertriglyceridemia. The study has demonstrated the presence of SNPs in four candidate genes among HIV patients exposed to ART in the Ghanaian population. SNPs were found to associate with dyslipidemia. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and its association with dyslipidemia.", "URL": "https://doi.org/10.1101/19004812"} |
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] | {"Title": "Identifying subtypes of a stigmatized medical condition", "Authors": "Gabashvili Irene S.", "Abstract": "Abstract Background Some conditions - such as obesity, depression and functional odor disorders - come with a social stigma. Understanding the etiology of these conditions helps to avoid stereotypes and find remedies. One of the major obstacles facing researchers, especially for those studying socially distressing metabolic malodor, is the difficulty in assembling biologically homogenous study cohorts. Objective The aim of this study was to examine phenotypic variance, self-reported data and laboratory tests for the purpose of identifying clinically relevant and etiologically meaningful subtypes of idiopathic body odor and the \u201cPeople are Allergic To Me\u201d (PATM) syndrome. Methods Participants with undiagnosed body odor conditions enrolled to participate in this research study initiated by a healthcare charity MEBO Research and sponsored by Wishart Research group at the Metabolomics Innovation Centre, University of Alberta, Canada. Primary outcomes were differences in metabolite concentrations measured in urine, blood and breath of test and control groups. Principal component analyses and other statistical tests were carried out for these measurements. Results While neither of existing laboratory tests could reliably predict chronic malodor symptoms, several measurements distinguished phenotypes at a significance level less than 5%. Types of malodor can be differentiated by self-reported consumption of (or sensitivity to) added sugars (p<0.01), blood alcohols after glucose challenge (especially ethanol: p<0.0005), urinary excretion of phenylalanine, putrescine, and combinations of blood or urine metabolites. Conclusions Our preliminary results suggest that malodor heterogeneity can be addressed by analyses of phenotypes based on patients\u2019 dietary and olfactory observations. Our studies highlight the need for more trials. Future research focused on comprehensive metabolomics and microbiome sequencing will play an important role in the diagnosis and treatment of malodor. Trial Registration The study discussed in the manuscript was registered as NCT02692495 at clinicaltrials.gov. The results were compared with our earlier study registered as NCT02683876.", "URL": "https://doi.org/10.1101/19005223"} |
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] | {"Title": "Nonlinear biomarker interactions in conversion from Mild Cognitive Impairment to Alzheimer\u2019s disease", "Authors": "Popescu Sebastian G., Whittington Alex, Gunn Roger N., Matthews Paul M., Glocker Ben, Sharp David J, Cole James H", "Abstract": "Abstract The multi-faceted nature of Alzheimer\u2019s disease means that multiple biomarkers (e.g., amyloid-\u03b2, tau, brain atrophy) can contribute to the prediction of clinical outcomes. Machine learning methods are a powerful way to identify the best approach to this prediction. However, it has been difficult previously to model nonlinear interactions between biomarkers in the context of predictive models. This is important as the mechanisms relating these biomarkers to the disease are inter-related and nonlinear interactions occur. Here, we used Gaussian Processes to model nonlinear interactions when combining biomarkers to predict Alzheimer\u2019s disease conversion in 48 mild cognitive impairment participants who progressed to Alzheimer\u2019s disease and 158 stable (over three years) people with mild cognitive impairment. Measures included: demographics, APOE4 genotype, CSF (amyloid-\u03b242, total tau, phosphorylated tau), neuroimaging markers of amyloid-\u03b2 deposition ([18 F ]florbetapir) or neurodegeneration (hippocampal volume, brain-age). We examined: (i) the independent value each biomarker has in predicting conversion; and (ii) whether modelling nonlinear interactions between biomarkers improved prediction performance. Despite relatively high correlations between different biomarkers, our results showed that each measured added complementary information when predicting conversion to Alzheimer\u2019s disease. A linear model predicting MCI group (stable versus progressive) explained over half the variance (R 2 = 0.51, P < 0.001); the strongest independently-contributing biomarker was hippocampal volume (R 2 = 0.13). Next, we compared the sensitivity of different models to progressive MCI: independent biomarker models, additive models (with no interaction terms), nonlinear interaction models. We observed a significant improvement ( P < 0.001) for various two-way interaction models, with the best performing model including an interaction between amyloid-\u03b2-PET and P-tau, while accounting for hippocampal volume (sensitivity = 0.77). Our results showed that closely-related biomarkers still contribute uniquely to the prediction of conversion, supporting the continued use of comprehensive biological assessments. A number of interactions between biomarkers were implicated in the prediction of Alzheimer\u2019s disease conversion. For example, the interaction between hippocampal atrophy and amyloid-deposition influences progression to Alzheimer\u2019s disease over and above their independent contributions. Importantly, nonlinear interaction modelling shows that although for some patients adding additional biomarkers may add little value (i.e., when hippocampal volume is high), but for others (i.e., with low hippocampal volume) further invasive and expensive testing is warranted. Our Gaussian Processes framework enables visual examination of these nonlinear interactions, allowing projection of individual patients into biomarker \u2018space\u2019, providing a way to make personalised healthcare decisions or stratify subsets of patients for recruitment into trials of neuroprotective interventions.", "URL": "https://doi.org/10.1101/19002378"} |
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] | {"Title": "Predicting the required pre-surgery blood volume in surgical patients based on machine learning", "Authors": "Li Ruilin, Han Xinyin, Sun Liping, Feng Yannan, Sun Xiaolin, He Xiaoyu, Zhang Yu, Zhu Haidong, Zhao Dan, Dai Chuangchuang, He Zhipeng, Chen Shanyu, Wang Xin, Li Weizhong, Chi Xuebin, Yu Yang, Niu Beifang, Wang Deqing", "Abstract": "Abstract Precisely predicting the required pre-surgery blood volume (PBV) in surgical patients is a formidable challenge in China. Inaccurate estimation is associate with excessive costs, postponed surgeries and adverse outcome after surgery due to in sufficient supply or inventory. This study aimed to predict required PBV based on machine learning techniques. 181,027 medical documents over 6 years were cleaned and finally obtained 92,057 blood transfusion records. The blood transfusion and surgery related factors of perioperative patients, surgeons experience volumes and the actual volumes of transfused RBCs were extracted. 6 machine learning algorithms were used to build prediction models. The surgery patients received allogenic RBCs or without transfusion, had total volume less than 10 units, or had the latest laboratory examinations of pre-surgery within 7 days were included, providing 118,823 data points. 39 predictive factors related to the RBCs transfusion were identified. Random forest model was selected to predict the required PBV of RBCs with 72.9% accuracy and strikingly improved the accuracy by 30.4% compared with surgeons experience, where 90% of data was used for training. We tested and demonstrated that both the data-driven models and the random forest model achieved higher accuracy than surgeons experience. Furthermore, we developed a computational tool, PTRBC, to precisely estimate the required PBV in surgical patients and we believe this tool will find more applications in assisting clinician decisions, not only confined to making accurate pre-surgery blood requirement predicting.", "URL": "https://doi.org/10.1101/19008045"} |
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] | {"Title": "The Mezurio smartphone application: Evaluating the feasibility of frequent digital cognitive assessment in the PREVENT dementia study", "Authors": "Lancaster Claire Dr, Blane Jasmine, Chinner Amy, Wolters Leona, Koychev Ivan Dr, Hinds Chris Dr", "Abstract": "Abstract Background Smartphones may significantly contribute to the detection of early cognitive decline at scale by enabling remote, frequent, sensitive, economic assessment. Several prior studies have sustained engagement with participants remotely over a period of a week; extending this to a period of a month would clearly give greater opportunity for measurement. However, as such study durations are increased, so too is the need to understand how participant burden and scientific value might be optimally balanced. Objectives We explore the \u2018little but often\u2019 approach to assessment employed by the Mezurio app, interacting with participants every day for over a month. We aim to understand whether this extended remote study duration is feasible, and which factors might promote sustained participant engagement over such study durations. Methods Thirty-five adults (aged 40-59 years) with no diagnosis of cognitive impairment were prompted to interact with the Mezurio smartphone app platform for up to 36 days, completing short, daily episodic memory tasks in addition to optional executive function and language tests. A subset ( n =20) completed semi-structured interviews focused on their experience using the app. Results Average compliance with the schedule of learning for subsequent memory test was 80%, with 88% of participants still actively engaged by the final task. Thematic analysis of participants\u2019 experiences highlighted schedule flexibility, a clear user-interface, and performance feedback as important considerations for engagement with remote digital assessment. Conclusions Despite the extended study duration, participants demonstrated high compliance with the tasks scheduled and were extremely positive about their experiences. Long durations of remote digital interaction are therefore definitely feasible, but only when careful attention is paid to the design of the users\u2019 experience.", "URL": "https://doi.org/10.1101/19005124"} |
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] | {"Title": "Novel delivery of cellular therapy to reduce ischaemia reperfusion injury in kidney transplantation", "Authors": "Thompson Emily R, Bates Lucy, Ibrahim Ibrahim K, Sewpaul Avinash, Stenberg Ben, McNeill Andrew, Figueiredo Rodrigo, Girdlestone Tom, Wilkins Georgina C, Irwin Ellen A, Tingle Samuel J, Scott William E III, Lamos Henrique, Mellor Andrew L., Roobrouck Valerie D., Ting Anthony E., Hosgood Sarah A, Nicholson Michael L, Fisher Andrew J, Ali Simi, Sheerin Neil S, Wilson Colin H", "Abstract": "Abstract Ex-vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimise organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC \u00ae ) possess potent immunomodulatory properties which could prove beneficial in minimising subsequent ischaemia reperfusion injury. We investigated the potential reconditioning capability of MAPC cells in kidney NMP. Methods Pairs (5) of human kidneys from the same donor were simultaneously perfused for 7 hours. The right or left kidney was randomly allocated to receive MAPC treatment. Serial samples of perfusate, urine and tissue biopsies were taken for comparison with the control paired kidney. Results MAPC-treated kidneys demonstrated improved urine output (p<0.01), decreased expression of the kidney injury biomarker NGAL (p<0.01), improved microvascular perfusion on contrast enhanced ultrasound (cortex p<0.05, medulla p<0.01), downregulation of IL-1\u03b2 (p<0.05) and upregulation of IL-10 (p<0.05) and Indolamine-2, 3-dioxygenase (p<0.05). A mouse model of intraperitoneal chemotaxis demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (p<0.01). Immunofluorescence revealed pre-labelled MAPC cells home to the perivascular space in the kidneys during NMP. MAPC therapy was not associated with detrimental physiological or embolic events. Conclusion We report the first successful delivery of cellular therapy to a kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant functional parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to clinical transplantation. One Sentence Summary Ex-vivo reconditioning of human kidneys using Multipotent Adult Progenitor Cell therapy delivered during normothermic machine perfusion.", "URL": "https://doi.org/10.1101/19005546"} |
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] | {"Title": "Against Empathy: distinct correlates of empathy and compassion with burnout and affective symptoms in health professionals and students", "Authors": "Romani-Sponchiado Aline, Jordan Matthew R., Stringaris Argyris, Salum Giovanni Abrah\u00e3o", "Abstract": "Concern for the well-being of medical professionals has increased considering the high rates of depression and suicidal ideation observed among medical students and residents. However, the causes of such psychological distress among health professionals are still unknown.\nOne possibility is that such negative outcomes arise from individual differences in how clinicians respond to the emotional states of their patients: while some tend respond with empathy (feeling what others feel), others tend respond with compassion (caring about what others feel). The aim of this study is to investigate the hypothesis that empathy is related to higher levels of burnout and affective symptoms, while compassion is related to lower levels of these outcomes.\nWe surveyed 464 undergraduate students and professionals in medicine (34.3%), psychology (47%) and nursing (18.8%), 79.7% female, with a median age of 23.3. The survey included the concern and perspective taking subscales from the Interpersonal Reactivity Index (IRI); empathy and behavioral contagion from the Empathy Index (EI); the depression, anxiety, and anger subscales from PROMIS; and the Medical Student Well-Being Index (MSWBI).\nEmpathy was associated with higher symptoms of burnout, depression, anxiety and anger; while higher levels of compassion were associated with lower levels of these outcomes.\nOur findings provide new evidence that the well-being of medical professionals might be affected differently depending on socio-emotional traits relevant to emotional connection.", "URL": "https://doi.org/10.1101/19005231"} |
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] | {"Title": "From frail to fit after allogeneic hematopoietic cell transplantation: Scope of the problem and a strength-based solution", "Authors": "Sweetnam Jason, Twohey Eric, Skendzel Sasha, Stingle John, Arora Mukta, Baraki Austin, Cao Qing, Grillo Sonya, Holtan Shernan G.", "Abstract": "Abstract Background Frailty is a common but underdiagnosed syndrome among long-term survivors of allogeneic hematopoietic cell transplantation (HCT). Conditions such as malnutrition, fatigue, and weakness may suggest frailty despite patients not receiving a formal diagnosis. Furthermore, the optimal interventions to overcome frailty in long-term survivors of allogeneic HCT is not yet established. Patients and Methods This study consists of a retrospective and prospective component. First, we completed a retrospective review using diagnosis data from the electronic medical record to estimate the prevalence of components of frailty in 1077 recipients of allogeneic HCT through 5 years post-transplant. Second, we developed a community-based pilot study of strength training for long-term survivors of allogeneic HCT that addressed several common barriers exercise engagement and adherence. Four allogeneic HCT recipients (2 males, 2 females) and 4 controls (2 males, 2 females) completed the strength training pilot study, consisting of a baseline assessment, 10 weeks of personalized and supervised strength programming at least once weekly as a group, and an end-of-study assessment to measure progress in strength, body composition, and a standardized measure of self-efficacy. Results Despite a lack of a formal diagnosis, approximately 80% of HCT recipients in this series received a diagnosis of a component of frailty (weakness, fatigue, or malnutrition), and over 1/3 of HCT recipients had symptoms extending beyond 1 year. Over the course of the strength training pilot study, both pre-frail/frail allogeneic HCT recipients and healthy controls doubled their total strength, lost body fat, and gained muscle mass. Self-efficacy improved from baseline in allogeneic HCT recipients after the strength training pilot program. Discussion Based upon the prevalence of frailty-related diagnoses among long-term survivors of HCT, a comprehensive mitigation strategy needs to be developed for this population. A community-based strength training program that includes a personalized component, a group setting, and caregiver/partner involvement appears feasible and overcomes several established barriers to exercise engagement and adherence.", "URL": "https://doi.org/10.1101/19010397"} |
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] | {"Title": "Independently Carriage of IL-1RN*2 Allele Associated with Increased Risk of Gastric Cancer in The Sudanese Population", "Authors": "Idris Abeer Babiker, Ataelmanan Amany Eltayib, Eltaher Sulafa Mohamed, Idris Einas Babiker, Osman Arbab Bashir M., Idris Ahmed Ibn, Mansour Mohamed, Ibrahim El-Amin Mohamed, Hassan Mohamed A.", "Abstract": "Abstract Background Helicobacter pylori is responsible for gastric cancer in approximately tens of millions of patients. Gastric cancer in Sudan represents one of the top causing death among cancers with about 686 cases per year and a 2.7 % mortality rate. IL-1RN VNTR polymorphism has been reported to increase the risk of gastric cancer. Objective The purpose of this study was to assess the association of the 86 bp VNTR polymorphism of IL- 1RN gene and the susceptibility to H. pylori infection and gastric cancer in the Sudanese population. Materials and methods Genomic DNA was extracted from 114 subjects. Of whom 60 had gastritis and duodenitis, 26 had a peptic ulcer, 16 had gastric cancer and 12 had normal gastroscopy findings. H. pylori infection was investigated by specific 16S rRNA . And IL-1RN VNTR polymorphism at intron 2 was genotyped using the PCR method and direct sequencing for random samples. Results The positive H. pylori infection rate among participants was 47.37%. There is a lack of a significant difference in IL- 1RN genotype with H. pylori infection (p-value=1.0000). The IL-1 RN L/L genotype was significantly more frequent in a patient with benign disorders (gastritis or duodenitis or peptic ulcer), Odd=6.000 (95% CI =1.750-20.57, P=0.0056). While the heterozygote genotype 2/L was associated with an increased risk of gastric cancer with OR = 12.83 (95% CI = 1.261-130.6, P=0.0302). Conclusion Independently carriage of IL-1RN *2 allele was associated with increased risk of gastric cancer in the Sudanese population. Notwithstanding the relatively small sample size of the study population, our findings show that the host genetic can be a useful tool for identifying high-risk individuals among dyspeptic patients; and also underscore the role played by host genetics in gastric carcinogenesis. To the best of our knowledge, this is the first study in Sudan concerning this issue.", "URL": "https://doi.org/10.1101/19013573"} |
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] | {"Title": "Subacute effects of the psychedelic ayahuasca on the salience and default mode networks", "Authors": "Pasquini Lorenzo, Palhano-Fontes Fernanda, Araujo Draulio B.", "Abstract": "Abstract Background Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks\u2019 functional organization. Even less is known on the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networks supporting higher-order affective and self-referential functions 24h after a single session with the psychedelic ayahuasca. Methods We leveraged task-free functional magnetic resonance imaging data one day before and one day after a randomized placebo-controlled trial exploring the effects of ayahuasca in na\u00efve healthy participants (21 placebo/22 ayahuasca). We derived intra- and inter-network functional connectivity of the salience, default mode, visual, and sensorimotor networks, and assessed post-session connectivity changes between the ayahuasca and placebo groups. Connectivity changes were associated with Hallucinogen Rating Scale scores assessed during the acute effects. Results Our findings revealed increased anterior cingulate cortex connectivity within the salience network, decreased posterior cingulate cortex connectivity within the default mode network, and increased connectivity between the salience and default mode networks one day after the session in the ayahuasca group compared to placebo. Connectivity of primary sensory networks did not differ between-groups. Salience network connectivity increases correlated with altered somesthesia scores, decreased default mode network connectivity correlated with altered volition scores, and increased salience-default mode network connectivity correlated with altered affect scores. Conclusion These findings provide preliminary evidence for subacute functional changes induced by the psychedelic ayahuasca on higher-order cognitive brain networks that support interoceptive, affective, and self-referential functions.", "URL": "https://doi.org/10.1101/19007542"} |
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] | {"Title": "Disruptive Mood Dysregulation Disorder: symptomatic and syndromic thresholds and diagnostic operationalization", "Authors": "Laporte Paola Paganella, Matijasevich Alicia, Munhoz Tiago N., Santos In\u00e1 S., Barros Alu\u00edsio J. D., Pine Daniel Samuel, Rohde Luis Augusto, Leibenluft Ellen, Abrah\u00e3o Salum Giovanni", "Abstract": "Abstract Objective The aim of this study is to identify the most appropriate threshold for Disruptive Mood Dysregulation Disorder (DMDD) diagnosis and the impact of potential changes in diagnostic rules on prevalence levels in the community. Method Trained psychologists evaluated 3,562 pre-adolescents/early adolescents from the 2004 Pelotas Birth Cohort with the Development and Well-Being Behavior Assessment (DAWBA). The clinical threshold was assessed in three stages: symptomatic, syndromic and clinical operationalization. The symptomatic threshold identified the response category in each DAWBA item which separates normative misbehavior from a clinical indicator. The syndromic threshold identified the number of irritable mood and outbursts needed to capture pre-adolescents/early adolescents with high symptom levels. Clinical operationalization compared the impact of AND/OR rules for combining irritable mood and outbursts on impairment and levels of psychopathology. Results At the symptomatic threshold, most irritable mood items were normative in their lowest response categories and clinically significant in their highest response categories. For outbursts some indicated a symptom even when present at only a mild level, while others did not indicate symptoms at any level. At the syndromic level, a combination of 2 out of 7 irritable mood and 3 out of 8 outburst indicators accurately captured a cluster of individuals with high level of symptoms. Analysis combining irritable mood and outbursts delineated non-overlapping aspects of DMDD, providing support for the OR rule in clinical operationalization. The best DMDD criteria resulted in a prevalence of 3%. Conclusion Results provide information for initiatives aiming to provide data-driven and clinically oriented operationalized criteria for DMDD.", "URL": "https://doi.org/10.1101/19002436"} |
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] | {"Title": "Molecular Epidemiology, Diagnostics and Mechanisms of Antibiotic Resistance in Mycobacterium tuberculosis complex in Africa: A Systematic Review of Current Reports", "Authors": "Sekyere John Osei, Reta Melese Abate, Maningi Nontuthuko Excellent, Fourie Petrus Bernard", "Abstract": "Abstract Background Tuberculosis (TB) remains a main global public health problem. However, a systematic review of TB resistance epidemiology in Africa is wanting. Methods A comprehensive systematic search of PubMed, Web of Science and ScienceDirect for English research articles reporting on the molecular epidemiology of Mycobacterium tuberculosis complex resistance in Africa from January 2007 to December 2018 was undertaken. Results and conclusion Qualitative and quantitative synthesis were respectively undertaken with 232 and 186 included articles, representing 32 countries. TB monoresistance rate was highest for isoniazid (59%) and rifampicin (27%), particularly in Zimbabwe (100%), Swaziland (100%), and Sudan (67.9%) whilst multidrug resistance (MDR) rate was substantial in Zimbabwe (100%), Sudan (34.6%), Ivory Coast (24.5%) and Ethiopia (23.9%). Resistance-conferring mutations were commonly found in katG (n=3694), rpoB (n=3591), rrs (n=1272), inhA (n=1065), pncA (n=1063) and embB (n=705) in almost all included countries: S 315 G/I/N/R/T, V 473 D/F/G/I, Q 471 H/Q/R/Y, S 303 C/L etc. in katG; S 531 A/F/S/G, H 526 A/C/D/G, D 516 A/E/G etc. in rpoB; A 1401 G, A 513 C etc. in rrs; C 15 T, G 17 A/T, -A 16 G etc. in inhA; Ins 456 C, Ins 172 G, L 172 P, C 14 R, Ins 515 G etc in pncA . Commonest lineages and families such as T (n=8139), LAM (n=5243), Beijing (n=5471), Cameroon (n=3315), CAS (n=2021), H (n=1773) etc., with the exception of T, were not fairly distributed; Beijing, Cameroon and CAS were prevalent in South Africa (n=4964), Ghana (n=2306), and Ethiopia/Tanzania (n=799/635) respectively. Resistance mutations were not lineage-specific and sputum (96.2%) were mainly used for diagnosing TB resistance using the LPA (38.5%), GeneXpert (17.2%), whole-genome sequencing (12.3%) and PCR/amplicon sequencing (9%/23%). Intercountry spread of strains were limited while intra-country dissemination was common. TB resistance and its diagnosis remain a major threat in Africa, necessitating urgent action to contain this global menace.", "URL": "https://doi.org/10.1101/19008052"} |
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] | {"Title": "Systematic Review and Meta-Analysis of the Associations Between Body Mass Index, Prostate Cancer, Advanced Prostate Cancer and Prostate Specific Antigen", "Authors": "Harrison Sean, Tilling Kate, Turner Emma L., Martin Richard M., Lennon Rosie, Lane J. Athene, Donovan Jenny L., Hamdy Freddie C., Neal David E., Bosch J.L.H. Ruud, Jones Hayley E.", "Abstract": "Abstract Purpose The relationship between body-mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA. Methods We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome. Results In the meta-analyses with continuous BMI, a 5 kg/m 2 increase in BMI was associated with a percentage change in PSA of \u22125.88% (95% CI \u22126.87% to \u22124.87%). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI \u22125.57% to \u22121.23%), and obese men were 12.9% lower (95% CI \u221215.2% to \u221210.7%). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations. Conclusion There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.", "URL": "https://doi.org/10.1101/19005421"} |
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] | {"Title": "Impairment of dual-task gait dynamics in older adults with mild cognitive impairment: Relationships to neuropsychological status, fitness and brain morphology", "Authors": "Hawkins Tess C, Samuel Rebecca, Fiatarone Singh Maria A, Gates Nicola, Wilson Guy C, Jain Nidhi, Meiklejohn Jacinda, Brodaty Henry, Wen Wei, Singh Nalin, Baune Bernhard T, Suo Chao, Baker Michael K, Foroughi Nasim, Wang Yi, Sachdev Perminder S, Valenzuela Michael J, Hausdorff Jeffrey M, Mavros Yorgi", "Abstract": "ABSTRACT Background Individuals with Mild Cognitive Impairment (MCI) have more gait variability under dual-task conditions than cognitively healthy adults. However, characteristics associated with this susceptibility of gait to dual-task stress are unknown. Methods Testing was performed at baseline in the Study of Mental And Resistance Training (SMART). Ninety-three adults with MCI (age 70\u00b16.8 years; 66.6% female) performed a single- and dual-task walk (cognitive distractor=letter fluency), in random order. Linear and non-linear gait variability were measured using force-sensitive insoles. Cognitive performance during dual-tasking was assessed by the number of correct words vocalized. Cognitive function, brain Magnetic Resonance Imaging (MRI), muscle strength, aerobic capacity, body composition, physical and psychosocial function were also assessed as potential correlates of gait dynamics. Results Gait dynamics worsened during dual-tasking, with decrements in both stride time variability (p<0.001) and detrended fluctuation analysis (DFA) (p=0.001). Lower aerobic capacity and thinner posterior cingulate cortex were associated with greater decrements in DFA (p<0.05). Smaller hippocampal volume, worse psychological well-being and poorer static balance were associated with greater decrements in stride time variability (p<0.05). By contrast, cognitive performance did not change under dual-task conditions compared to seated testing (p=0.13). Conclusions Under dual-task conditions, participants with MCI preserved their cognitive performance at the expense of gait stability. Decrements in dual-tasking gait were associated with lower aerobic fitness, balance, psychological well-being, and brain volume in cognitively-relevant areas of the posterior cingulate and hippocampus, all potentially modifiable characteristics. Trials of targeted interventions are needed to determine the potential plasticity of gait variability in high-risk cohorts.", "URL": "https://doi.org/10.1101/19005249"} |
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] | {"Title": "Natural Language Processing for Mimicking Clinical Trial Recruitment in Critical Care: A Semi-automated Simulation Based on the LeoPARDS Trial", "Authors": "Tissot Hegler, Shah Anoop, Agbakoba Ruth, Folarin Amos, Romao Luis, Brealey David, Harris Steve, Roguski Lukasz, Dobson Richard, Asselbergs Folkert", "Abstract": "Abstract Clinical trials often fail on recruiting an adequate number of appropriate patients. Identifying eligible trial participants is a resource-intensive task when relying on manual review of clinical notes, particularly in critical care settings where the time window is short. Automated review of electronic health records has been explored as a way of identifying trial participants, but much of the information is in unstructured free text rather than a computable form. We developed an electronic health record pipeline that combines structured electronic health record data with free text in order to simulate recruitment into the LeoPARDS trial. We applied an algorithm to identify eligible patients using a moving 1-hour time window, and compared the set of patients identified by our approach with those actually screened and recruited for the trial. We manually reviewed clinical records for a random sample of additional patients identified by the algorithm but not identified for screening in the original trial. Our approach identified 308 patients, of whom 208 were screened in the actual trial. We identified all 40 patients with CCHIC data available who were actually recruited to LeoPARDS in our centre. The algorithm identified 96 patients on the same day as manual screening and 62 patients one or two days earlier. Analysis of electronic health records incorporating natural language processing tools could effectively replicate recruitment in a critical care trial, and identify some eligible patients at an earlier stage. If implemented in real-time this could improve the efficiency of clinical trial recruitment.", "URL": "https://doi.org/10.1101/19005603"} |
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] | {"Title": "[Knowledge and attitudes regarding infant BLS among babysitters and nursemaids in north rural Jordan]", "Authors": "Raffee Liqaa, Hamadneh Shereen, Kassab Manal, Almomani Fidaa, Hamadneh Jehan, AlBashtawy Mohammed, Obeidat Rawan A., Almazloom Othman", "Abstract": "Abstract Background There is a lack of national data related to the public knowledge and attitudes concerning Basic Life Support (BLS) for an infant. This study is the first to assess the knowledge and attitude regarding infant BLS among babysitters and nursemaids who are working in registered nurseries in North Jordan. Methods A semi-structured questionnaire was conducted among a convenience sample of 77 child caretakers (babysitters and nursemaids) who were looking after infants in registered nurseries in north of Jordan. Results The findings show that the majority of participants were not aware of skills for managing foreign body aspiration (or CPR) among infants, while more than two-thirds of them never attended training and or education sessions regarding managing foreign body aspiration among infants. Conclusions This research strongly recommends training for babysitters and care center staff. The findings of this study indicated that caregivers in Jordanian kindergartens and nurseries lack awareness regarding safe infant care. As such, there is a lack of basic skills for resuscitation in urgent cases; which can increase the risk of sudden and unexpected child death. Accordingly, the infant life support course is highly recommended for babysitters and nursemaids. Health care professionals could help to implement infant basic life support training courses through local community basic service centers, non-governmental organizations, local associations, universities and health colleges through providing workshops that aim at enhancing knowledge and skills for infant BLS among caregivers and babysitters.", "URL": "https://doi.org/10.1101/19014175"} |
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] | {"Title": "A Genome-Wide Association Study of the Frailty Index Highlights Synaptic Pathways in Aging", "Authors": "Atkins Janice L, Jylh\u00e4v\u00e4 Juulia, Pedersen Nancy L, Magnusson Patrik K, Lu Yi, Wang Yunzhang, H\u00e4gg Sara, Melzer David, Williams Dylan M, Pilling Luke C", "Abstract": "ABSTRACT Frailty is a common geriatric syndrome, strongly associated with disability, mortality and hospitalisation. The mechanisms underlying frailty are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 19 and 45%. Understanding the genetic determinants and biological mechanisms underpinning frailty may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) of a frailty index (FI) in European descent participants from UK Biobank ( n =164,610, aged 60-70 years). FI calculation was based on 49 self-reported items on symptoms, disabilities and diagnosed diseases. We identified 26 independent genetic signals at 24 loci associated with the FI ( p <5*10 \u22128 ). Many of these loci have previously been associated with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, three appear to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 14% (0.14, SE 0.006). A genetic risk score for the FI, derived solely from the UK Biobank data, was significantly associated with FI in the Swedish TwinGene study ( n =10,616, beta: 0.11, 95% CI: 0.02-0.20, p =0.015). In pathway analysis, genes associated with synapse function were significantly enriched ( p <3*10 \u22126 ). We also used Mendelian randomization to identify modifiable traits and exposures that may affect the risk of frailty, with a higher educational attainment genetic risk score being associated with a lower risk of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on synapse maintenance pathways.", "URL": "https://doi.org/10.1101/19007559"} |
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] | {"Title": "Considerations in the deployment of novel universal vaccines against epidemic and pandemic influenza", "Authors": "Arinaminpathy N, Riley S, Barclay W.S, Saad-Roy C, Grenfell B", "Abstract": "Abstract There is increasing interest in the development of new, \u2018universal\u2019 influenza vaccines (UIV) that - unlike current vaccines - are effective against a broad range of seasonal influenza strains, as well as against novel pandemic viruses. Even where these vaccines do not block infection, they can moderate clinical severity, reducing morbidity and mortality while potentially also reducing opportunities for transmission. Previous modelling studies have illustrated the potential epidemiological benefits of UIVs, including their potential to mitigate pandemic burden. However, these new vaccines could shape population immunity in complex ways. Here, using mathematical models of influenza transmission, we illustrate two types of unintended consequences that could arise from their future deployment. First, by reducing the amount of infection-induced immunity in a population without fully replacing it, a seasonal UIV programme may permit larger pandemics than in the absence of vaccination. Second, the more successful a future UIV programme is in reducing transmission of seasonal influenza, the more vulnerable the population could become to the emergence of a vaccine-escape variant. These risks could be mitigated by optimal deployment of any future UIV vaccine: namely, the use of a combined vaccine formulation (incorporating conventional as well as multiple universal antigenic targets), and by achieving sufficient population coverage to compensate for reductions in infection-induced immunity. As early candidates of UIVs approach advanced clinical trials, there is a need to monitor their characteristics in such a way that is focused on their potential impact. This work offers a first step in this direction.", "URL": "https://doi.org/10.1101/19002485"} |
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] | {"Title": "Prediction of Suicidal Ideation in the Canadian Community Health Survey - Mental Health Component Using Deep Learning", "Authors": "Desai Sneha, Tanguay-Sela Myriam, Benrimoh David, Fratila Robert, Brown Eleanor, Perlman Kelly, John Ann, DelPozo-Banos Marcos, Low Nancy, Israel Sonia, Palladini Lisa, Turecki Gustavo", "Abstract": "Abstract Introduction Suicidal ideation (SI) is prevalent in the general population, and is a prominent risk factor for suicide. However, predicting which patients are likely to have SI remains a challenge. Deep Learning (DL) may be a useful tool in this context, as it can be used to find patterns in complex, heterogeneous, and incomplete psychiatric datasets. An automated screening system for SI could help prompt clinicians to be more attentive to patients at risk for suicide. Methods Using the Canadian Community Health Survey - Mental Health Component, we trained a DL model based on 23,859 survey responses to predict lifetime SI on an individual patient basis. Models were created to predict both lifetime and last 12 month SI. We reduced 582 possible model parameters captured by the survey to 96 and 21 feature versions of the models. Models were trained using an undersampling procedure that balanced the training set between SI and non-SI respondents; validation was done on held-out data. Results AUC was used as the main model metric. For lifetime SI, the 96 feature model had an AUC of 0.79 and the 21 feature model had an AUC of 0.75. For SI in the last 12 months the 96 feature model had an AUC of 0.76 and the 21 feature model had an AUC of 0.69. DL outperformed random forest classifiers. Discussion Although requiring further study to ensure clinical relevance and sample generalizability, this study is a proof-of-concept for the use of DL to improve prediction of SI. This kind of model would help start conversations with patients which could lead to improved care and, it is hoped, a reduction in suicidal behavior.", "URL": "https://doi.org/10.1101/19010413"} |
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] | {"Title": "Changes in association between school foods and child and adolescent dietary quality during implementation of the Healthy, Hunger-Free Kids Act of 2010", "Authors": "Berger Aaron T., Widome Rachel, Erickson Darin J., Laska Melissa N., Harnack Lisa J.", "Abstract": "Abstract Purpose To estimate the effect of Healthy, Hunger-Free Kids Act of 2010 (HHFKA) implementation on dietary quality of all US school-aged children and adolescents, and examine whether those effects differed by demographic group. Methods We used survey regression on 2007-2016 National Health and Nutrition Examination Survey (NHANES) data to estimate the proportion of energy intake from school foods and the association between school food intake and dietary quality, before and after HHFKA passage/implementation. To account for demographic changes in the US population over time, inverse probability weighting was employed. The product of the proportion of energy from school foods and the association between school food intake and dietary quality estimated the effect of HHFKA implementation on dietary quality. Results School food intake quantity remained stable during the study period. HHFKA implementation improved students\u2019 dietary quality by 4.3 Healthy Eating Index-2010 (HEI) points (95% CI: 2.5, 6.1) on days when school foods were eaten, and by 1.3 HEI points (95% CI: 0.73, 1.8) averaged over all days annually. Conclusions HHFKA implementation improved the total dietary quality of US school students. US students would benefit from eating school meals in the post-HHFKA era, and HHFKA regulations should not be relaxed.", "URL": "https://doi.org/10.1101/19005579"} |
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] | {"Title": "Setting Standards to Promote Artificial Intelligence in Colon Mass Endoscopic Sampling", "Authors": "Zheng Yueping, Su Ruizhang, Wang Wangyue, Meng Sijun, Xiao Hang, Zhang Wen, Xu Haineng, Bu Yemei, Zhong Yuhuan, Zhang Yi, Qiu Hesong, Qin Wenjuan, Zhang Yongxiu, Xu Wen, Chen Hong, Zhang Changhua, Wu Siqi, Han Zhaofang, Zheng Xiaofang, Zhu Huafen, Wu Shuisheng, Pan Wensheng, He Yulong, Hu Yiqun", "Abstract": "ABSTRACT Objective Artificial intelligence (AI) has undeniable values in detection, characterization, and monitoring of tumors during cancer imaging. However, major AI explorations in digestive endoscopy have not been systematically planned, and more important, most AI productions are based on Single-center Studies (ScSs). ScSs result in data scarcity, redundancy as well as island effects, which leads to some limitations in applying it on endoscopy. We investigate the disadvantages of picture processing which may effect the AI detection, and make improvements in AI detection and image recognition accuracy. Design Current investigation aggregates a total of 2,500 gastroenteroscopy samples from various hospitals in multiple regions and carries out deep learning. Results It is found that factors inconducive to AI recognition are common such as: (a) the gastrointestinal tract is not cleaned up completely; (b) shooting angle (from left to right and the top of polyp are unexposed clearly), shooting distance (too close or too far to shoot causes the lump to be unclear), shooting light (insufficient light source or overexposed light source in mass) and unstable shooting lead to poor quality of pictures. Conclusion We set standards for a multicenter cooperation involving three-level medical institutions from the provincial, municipal and county to improve the recognition accuracy as well as the diagnosis and treatment efficiency meanwhile.", "URL": "https://doi.org/10.1101/19008078"} |
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] | {"Title": "Evaluation of Patient-Level Retrieval from Electronic Health Record Data for a Cohort Discovery Task", "Authors": "Bedrick Steven D., Cohen Aaron M., Wang Yanshan, Wen Andrew, Liu Sijia, Liu Hongfang, Hersh William R.", "Abstract": "ABSTRACT Objective Growing numbers of academic medical centers offer patient cohort discovery tools to their researchers, yet the performance of systems for this use case is not well-understood. The objective of this research was to assess patient-level information retrieval (IR) methods using electronic health records (EHR) for different types of cohort definition retrieval. Materials and Methods We developed a test collection consisting of about 100,000 patient records and 56 test topics that characterized patient cohort requests for various clinical studies. Automated IR tasks using word-based approaches were performed, varying four different parameters for a total of 48 permutations, with performance measured using B-Pref. We subsequently created structured Boolean queries for the 56 topics for performance comparisons. In addition, we performed a more detailed analysis of 10 topics. Results The best-performing word-based automated query parameter settings achieved a mean B-Pref of 0.167 across all 56 topics. The way a topic was structured (topic representation) had the largest impact on performance. Performance not only varied widely across topics, but there was also a large variance in sensitivity to parameter settings across the topics. Structured queries generally performed better than automated queries on measures of recall and precision, but were still not able to recall all relevant patients found by the automated queries. Conclusion While word-based automated methods of cohort retrieval offer an attractive solution to the labor-intensive nature of this task currently used at many medical centers, we generally found suboptimal performance in those approaches, with better performance obtained from structured Boolean queries. Insights gained in this preliminary analysis will help guide future work to develop new methods for patient-level cohort discovery with EHR data.", "URL": "https://doi.org/10.1101/19005280"} |
10.1101/2019.12.09.19014183 | [
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] | {"Title": "A polygenic risk score for rheumatoid arthritis sheds light on the Prevotella association", "Authors": "Wells Philippa M, Adebayo Adewale S, Freidin Maxim B, Finckh Axel, Strowig Till, Lesker Till Robin, Alpizar-Rodriguez Deshire, Gilbert Benoit, Kirkham Bruce, Cope Andrew P, Steves Claire J, Williams Frances M K", "Abstract": "Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with reduced life expectancy. It is heritable and an extensive repertoire of genetic variants have been identified. The gut microbiota may represent an environmental risk factor for RA. Indeed, Prevotella copri is a candidate keystone species, but whether it lies on the causal pathway for disease or is simply a bystander reflecting host-genetic predisposition to RA, remains to be determined. The study of disease-microbiota associations may be confounded by the presence of the disease of interest or by its treatment. To circumvent this issue, we assessed whether known RA risk alleles were associated with the gut microbiota, in a large who do not have RA. Methods Blood and stool acquired from volunteers from TwinsUK were used for genotyping and assessment of the gut microbiota, respectively. A weighted polygenic risk score (PRS) for RA was calculated in 1650 unaffected twins from the TwinsUK cohort, based on 233 published GWAS-identified published RA associated single nucleotide polymorphisms (SNPs). Amplicon sequence variants (ASVs) were generated from 16S rRNA sequencing of stool samples and assessed for association with RA PRS. Confirmation of findings was performed using an independent sample comprised of first-degree relatives of RA patients from the SCREEN-RA cohort (n=133). Findings We found that Prevotella spp was positively associated with RA PRS in TwinsUK participants (p.adj<1e-7). This finding was validated in SCREEN-RA participants carrying the shared epitope risk alleles (p.adj=1.12e-3). An association of Prevotella spp . with pre-clinical RA phases was also demonstrated (p.adj=0.021). Interpretation Prevotella in the gut microbiota is associated with RA genotype in the absence of RA, as well as in subjects at high risk of developing RA. This work suggests that host genotype is associated with microbiota profile prior to disease onset. Research in context Evidence before this study? Prevotella copri is increased within the gut microbiota in rheumatoid arthritis (RA) patients, predominantly those with early disease, before treatment is initiated. Prevotellaceae (family) has been demonstrated to be increased in pre-clinical RA cases compared to controls. Prevotella copri is posited to be an inflammatory driver, contributing to RA pathology by promoting a pro-inflammatory cytokine milieu. What does this study add? This study is the first to demonstrate that, in a large human cohort, carrying genetic risk factors for RA is associated with a higher abundance of Prevotella spp . in the absence of RA. How might this impact on clinical practice or future developments This work suggests that any potential causal role of Prevotella spp . occurs very early in disease development. Strategies to intervene should target early or asymptomatic at-risk groups", "URL": "https://doi.org/10.1101/2019.12.09.19014183"} |
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] | {"Title": "The genetic and clinical landscape of nanophthalmos in an Australian cohort", "Authors": "Siggs Owen M, Awadalla Mona S, Souzeau Emmanuelle, Staffieri Sandra E, Kearns Lisa S, Laurie Kate, Kuot Abraham, Qassim Ayub, Edwards Thomas L, Coote Michael A, Mancel Erica, Walland Mark J, Dondey Joanne, Galanopoulous Anna, Casson Robert J, Mills Richard A, MacArthur Daniel G, Ruddle Jonathan B, Burdon Kathryn P, Craig Jamie E", "Abstract": "Abstract Purpose Refractive error is caused by a disparity between the axial length and focusing power of the eye. Nanophthalmos is a rare ocular abnormality in which both eyes are abnormally small, typically causing extreme hyperopic refractive error, and associated with an increased risk of angle-closure glaucoma. Methods A cohort of 40 individuals from 13 unrelated nanophthalmos kindreds were recruited, with 11 probands subjected to exome sequencing. Results Nine probands (69.2%) were assigned a genetic diagnosis, with variants in PRSS56 (4), MFRP (3), and previously reported variants in TMEM98 (1) and MYRF (1). Two of the four PRSS56 probands harboured the previously described c.1066dupC frameshift variant implicated in over half of all reported PRSS56 kindreds, with surrounding haplotypes distinct from each other, and from a previously reported Tunisian c.1066dupC haplotype. Individuals with a genetic diagnosis had shorter mean axial lengths ( P =7.22\u00d710 \u22129 ) and more extreme hyperopia ( P =0.0005) than those without a genetic diagnosis, with recessive forms associated with the shortest axial lengths and highest hyperopia. All individuals with an axial length below 18 mm in their smaller eye (17/17) were assigned a genetic diagnosis. Conclusions These findings detail the genetic architecture of nanophthalmos in an Australian cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.", "URL": "https://doi.org/10.1101/19013599"} |
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] | {"Title": "Towards accurate and unbiased imaging based differentiation of Parkinson\u2019s Disease, Progressive Supranuclear Palsy and Corticobasal Syndrome", "Authors": "Correia Marta M, Rittman Tim, Barnes Christopher L, Coyle-Gilchrist Ian T, Ghosh Boyd, Hughes Laura E, Rowe James B", "Abstract": "Abstract The early and accurate differential diagnosis of parkinsonian disorders is still a significant challenge for clinicians. In recent years, a number of studies have used MRI data combined with machine learning and statistical classifiers to successfully differentiate between different forms of Parkinsonism. However, several questions and methodological issues remain, to minimise bias and artefact-driven classification. In this study we compared different approaches for feature selection, as well as different MRI modalities, with well matched patient groups and tightly controlling for data quality issues related to patient motion. Our sample was drawn from a cohort of 69 healthy controls, and patients with idiopathic Parkinson\u2019s disease (n=35, PD), Progressive Supranuclear Palsy Richardson\u2019s syndrome (n=52, PSP) and corticobasal syndrome (n=36, CBS). Participants underwent standardised T1-weighted MPRAGE and diffusion-weighted MRI. We compared two different methods for feature selection and dimensionality reduction: whole-brain principal components analysis, and an anatomical region-of-interest based approach. In both cases, support vector machines were used to construct a statistical model for pairwise classification of healthy controls and patients. The accuracy of each model was estimated using a leave-two-out cross-validation approach, as well as an independent validation using a different set of subjects. Our cross-validation results suggest that using principal components analysis (PCA) for feature extraction provides higher classification accuracies when compared to a region-of-interest based approach. However, the differences between the two feature extraction methods were significantly reduced when an independent sample was used for validation, suggesting that the principal components analysis approach may be more vulnerable to overfitting with cross-validation. Both T1-weighted and diffusion MRI data could be used to successfully differentiate between subject groups, with neither modality outperforming the other across all pairwise comparisons in the cross-validation analysis. However, features obtained from diffusion MRI data resulted in significantly higher classification accuracies when an independent validation cohort was used. Overall, our results support the use of statistical classification approaches for differential diagnosis of parkinsonian disorders. However, classification accuracy can be affected by group size, age, sex and movement artifacts. With appropriate controls and out-of-sample cross validation, diagnostic biomarker evaluation including MRI based classifiers can be an important adjunct to clinical evaluation.", "URL": "https://doi.org/10.1101/19007575"} |
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] | {"Title": "Obstructive sleep apnea, positive airway pressure treatment, and postoperative delirium: protocol for a retrospective observational study", "Authors": "King Christopher R, Escallier Krisztina, Ju Yo-El S., Lin Nan, Palanca Ben Julian A., McKinnon Sherry, Avidan Michael S Professor", "Abstract": "ABSTRACT Introduction Obstructive sleep apnea (OSA) is common among older surgical patients, and delirium is a frequent and serious postoperative complication. Emerging evidence suggests that OSA increases the risk for postoperative delirium. We hypothesize that OSA is an independent risk factor for postoperative delirium, and that in patients with OSA, perioperative adherence to positive airway pressure (PAP) therapy decreases the incidence of postoperative delirium and its sequelae. The proposed retrospective cohort analysis study will use existing datasets to: (i) describe and compare the incidence of postoperative delirium in surgical patients based on OSA diagnosis and treatment with PAP; (ii) assess whether preoperatively untreated OSA is independently associated with postoperative delirium; and (iii) explore whether preoperatively untreated OSA is independently associated with worse postoperative quality of life. The findings of this study will inform on the potential utility and approach of an interventional trial aimed at preventing postoperative delirium in patients with diagnosed and undiagnosed OSA. Methods and Analysis Observational data from existing electronic databases will be used, including over 100,000 surgical patients and \u223c10,000 intensive care unit (ICU) admissions. We will obtain the incidence of postoperative delirium in adults admitted postoperatively to the ICU who underwent structured preoperative assessment, including OSA diagnosis and screening. We will use doubly robust propensity score methods to assess whether untreated OSA independently predicts postoperative delirium. Using similar methodology, we will assess if untreated OSA independently predicts worse postoperative quality of life. Ethics and dissemination This study has been approved by the Human Research Protection Office at Washington University School of Medicine. We will publish the results in a peer-reviewed venue. Because the data is secondary and high risk for re-identification, we will not publicly share the data. Data will be destroyed after 1 year of completion of active IRB approved projects. Article summary Strengths and limitations of this study, (containing 5 short bullet points, no longer than one sentence each, that relate specifically to the methods) Our granular database includes routine structured preoperative screening for OSA, processed laboratory results, and verified comorbid diagnoses. We have limited information on the severity of most comorbidities, creating the possibility for substantial residual confounding. Our database includes near-universal and standardized nurse-driven delirium evaluations at multiple time-points as well as clinician diagnoses. Compared to prior studies, the large sample size will allow for more aggressive confounder adjustment utilizing linked structured medical histories, intraoperative records, and administrative data. Selection bias and confounding by indication are important limitations, which we will address using advanced statistical methods.", "URL": "https://doi.org/10.1101/19002501"} |
10.1101/19005892 | [
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] | {"Title": "Physical activity and risk of breast and endometrial cancers: a Mendelian randomization study", "Authors": "Baurecht Hansj\u00f6rg, Leitzmann Michael, O\u2019Mara Tracy, Thompson Deborah J, Teumer Alexander, Baumeister Sebastian E.", "Abstract": "A bstract Importance The causality of the association between physical activity and risk of breast and endometrial cancers is uncertain because available evidence is based exclusively on observational studies, which are potentially susceptible to confounding and reverse causation. Objective To investigate whether increased physical activity is causally associated with decreased risk of breast and endometrial cancers, using a two-sample Mendelian randomization study design. Design, Setting, and Participants Genome-wide association studies of physical activity, breast cancer, and endometrial cancer, published up to April 31, 2019, were identified using PubMed and the GWAS catalog. Twelve single nucleotide polymorphisms (SNP) known at P < 5 \u00d7 10 \u22128 to be associated with accelerometer-assessed or self-reported physical activity served as instrumental variables. Genetic summary data from four large consortia provided SNP-outcome associations [Breast Cancer Association Consortium; Discovery, Biology and Risk of Inherited Variants in Breast Cancer Consortium; Endometrial Cancer Association Consortium]. Main Outcomes and Measures The primary outcomes were risk of breast cancer and risk of endometrial cancer. Secondary outcomes were estrogen receptor positive (ER+) and ER-breast cancers. Odds ratios (ORs) and 95% confidence intervals (CIs) per mean acceleration in milli-gravities of accelerometer-assessed physical activity and per one standard deviation (1-SD) increase in metabolic-equivalent (MET)-minutes/week of self-reported moderate-to-vigorous physical activity were computed using the inverse variance weighted method. A series of sensitivity analyses addressed the potential impact of heterogeneity, pleiotropy, and outliers. Results Summary data were available for 122,977 breast cancers and 12,270 endometrial cancers. Genetic predisposition to increased accelerometer-assessed physical activity was associated with lower risk of breast and endometrial cancers. The associations (ORs [95% CI] per 1-SD increase in mean acceleration) were 0.88 (0.85-0.91) for breast cancer and 0.90 (0.83-0.97) for endometrial cancer. In addition, genetic predisposition to increased accelerometer-assessed physical activity was associated with lower risk of ER+ breast cancer. We found no evidence for an association between genetic predisposition to self-reported physical activity and risk of total breast cancer, breast cancer subtypes, or endometrial cancer. Conclusion and Relevance This first Mendelian randomization study shows that objectively-assessed physical activity plays a causal role in protecting against breast and endometrial cancers.", "URL": "https://doi.org/10.1101/19005892"} |
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] | {"Title": "Forecasting Seizure Risk over Days", "Authors": "Proix Timoth\u00e9e, Truccolo Wilson, Leguia Marc G., King-Stephens David, Rao Vikram R., Baud Maxime O.", "Abstract": "Abstract For persons with epilepsy, much suffering stems from the apparent unpredictability of seizures. Historically, efforts to predict seizures have sought to detect changes in brain activity in the seconds to minutes preceding seizures (pre-ictal period), a timeframe that limits preventative interventions. Recently, converging evidence from studies using chronic intracranial electroencephalography revealed that brain activity in epilepsy has a robust cyclical structure over hours (circadian) and days (multidien). These cycles organize pro-ictal states, hours-to days-long periods of heightened seizure risk, raising the possibility of forecasting seizures over horizons longer than the pre-ictal period. Here, using cEEG from 18 subjects, we developed point-process generalized linear models incorporating cyclical variables at multiple time-scales to show that seizure risk can be forecasted accurately over days in most subjects. Personalized risk-stratification days in advance of seizures is unprecedented and may enable novel preventative strategies.", "URL": "https://doi.org/10.1101/19008086"} |
10.1101/2019.12.13.19014217 | [
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] | {"Title": "Cerebrospinal fluid and plasma biomarkers in individuals at risk for genetic prion disease", "Authors": "Vallabh Sonia M, Minikel Eric Vallabh, Williams Victoria J, Carlyle Becky C, McManus Alison J, Wennick Chase D, Bolling Anna, Trombetta Bianca A, Urick David, Nobuhara Chloe K, Gerber Jessica, Duddy Holly, Lachmann Ingolf, Stehmann Christiane, Collins Steven J, Blennow Kaj, Zetterberg Henrik, Arnold Steven E", "Abstract": "ABSTRACT BACKGROUND Fluid biomarkers are important in the development of therapeutics to delay or prevent prion disease, but have not been systematically evaluated in pre-symptomatic individuals at risk for genetic prion disease. METHODS We recruited pre-symptomatic individuals with pathogenic mutations in the prion protein gene ( PRNP ; N=27) and matched controls (N=16), to donate cerebrospinal fluid (CSF) and blood at multiple timepoints to a cohort study at Massachusetts General Hospital. We quantified total prion protein (PrP) and real-time quaking-induced conversion (RT-QuIC) prion seeding activity in CSF, and the neuronal damage markers total tau (T-tau) and neurofilament light chain (NfL) in both CSF and plasma. We compared these markers cross-sectionally between mutation carriers and controls, evaluated short-term test-retest reliability over 2-4 months, and conducted a pilot longitudinal study over 10-20 months for a subset of participants. FINDINGS CSF PrP levels were stable on test-retest with a mean coefficient of variation of 7% both over 2-4 months in N=29 participants and over 10-20 months in N=10 participants. RT-QuIC was negative in 22/23 mutation carriers. The sole individual with positive RT-QuIC seeding activity at two study visits had steady CSF PrP levels and slightly increased tau and NfL concentrations compared with others, though still within the normal range, and remained asymptomatic one year later. Overall, tau and NfL showed no significant differences between mutation carriers and controls in either CSF or plasma. INTERPRETATION CSF PrP will be interpretable as a pharmacodynamic readout of the effects of a PrP-lowering therapeutic in pre-symptomatic individuals, and may serve as a surrogate biomarker in a \u201cprimary prevention\u201d trial paradigm. In contrast, current markers of prion seeding activity and of neuronal damage do not reliably cross-sectionally distinguish mutation carriers from controls, arguing against the feasibility of a \u201csecondary prevention\u201d paradigm in which trials specifically recruit pre-symptomatic participants with prodromal evidence of pathology.", "URL": "https://doi.org/10.1101/2019.12.13.19014217"} |
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] | {"Title": "Lower limb muscle activity underlying temporal gait asymmetry post-stroke", "Authors": "Rozanski Gabriela M., Huntley Andrew H., Crosby Lucas D., Schinkel-Ivy Alison, Mansfield Avril, Patterson Kara K.", "Abstract": "Abstract Objective Asymmetric walking after stroke is common, detrimental, and difficult to treat, but current knowledge of underlying physiological mechanisms is limited. This study investigated electromyographic (EMG) features of temporal gait asymmetry (TGA). Methods Participants post-stroke with or without TGA and control adults (n=27, 8, and 9, respectively) performed self-paced overground gait trials. EMG, force plate, and motion capture data were collected. Lower limb muscle activity was compared across groups and sides (more/less affected). Correlation between burst timing variables and asymmetry ratios was examined. Results Significant group by side interaction effects were found: fewer TGA group dorsiflexor bursts during swing (p=.0009), more affected plantarflexor stance activity ended early (p=.0006) and less affected dorsiflexor on/off time was delayed (p<.01) in persons with asymmetry compared to symmetric and normative controls. Less affected side EMG timing correlated most with swing time ratio (r=0.68-0.90, p<.001). Conclusions Temporal patterns of muscular activation, particularly about the ankle around the stance-to-swing transition period, are associated with TGA. The results may reflect specific impairments or compensations that affect locomotor coordination. Significance Neuromuscular underpinnings of spatiotemporal asymmetry have not been previously characterized. These novel findings may inform targeted therapeutic strategies to improve gait quality after stroke.", "URL": "https://doi.org/10.1101/19010421"} |
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] | {"Title": "Alien limb in the corticobasal syndrome: phenomenological characteristics and relationship to apraxia", "Authors": "Lewis-Smith David J., Wolpe Noham, Ghosh Boyd C.P., Rowe James B.", "Abstract": "ABSTRACT Alien limb refers to movements that seem purposeful but are independent of patients\u2019 reported intentions. Alien limb often co-occurs with apraxia in the corticobasal syndrome, and anatomical and phenomenological comparisons have led to the suggestion that alien limb and apraxia may be causally related as failures of goal-directed movements. Here, we characterised the nature of alien limb symptoms in patients with the corticobasal syndrome (n=30) and their relationship to limb apraxia. Twenty-five patients with progressive supranuclear palsy Richardson syndrome served as a disease-control group. Structured examinations of praxis, motor function, cognition and alien limb were undertaken in patients attending a regional specialist clinic. Twenty-eight patients with corticobasal syndrome (93%) demonstrated significant apraxia and this was often asymmetrical, with the left hand preferentially affected in 77% of patients. Moreover, 83% reported one or more symptoms consistent with alien limb. The range of these phenomena was broad, including changes in the sense of ownership and control as well as unwanted movements. Regression analyses showed no significant association between the severity of limb apraxia and both the occurrence of an alien limb and the number of alien limb phenomena reported. Bayesian estimation showed a low probability for a positive association between alien limb and apraxia, suggesting that alien limb phenomena are not likely to be related to severe apraxia. Our results shed light on the phenomenology of these disabling and as yet untreatable clinical features, with relevance to theoretical models of voluntary action.", "URL": "https://doi.org/10.1101/19013607"} |
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] | {"Title": "A deep learning approach with event-related spectral EEG data in attentional deficit hyperactivity disorder", "Authors": "Dubreuil-Vall Laura, Ruffini Giulio, Camprodon Joan A.", "Abstract": "Attention deficit hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder that affects 5% of the pediatric and adult population worldwide. The diagnosis remains essentially clinical, based on history and exam, with no available biomarkers. In this paper, we describe a deep convolutional neural network (DCNN) for ADHD classification derived from the time-frequency decomposition of electroencephalography data (EEG), particularly of event-related potentials (ERP) during the Flanker Task collected from 20 ADHD adult patients and 20 healthy controls (HC). The model reaches a classification accuracy of 88%, superior to resting state EEG spectrograms and with the key advantage, compared with other machine learning approaches, of avoiding the need for manual selection of EEG spectral or channel features. Finally, through the use of feature visualization techniques, we show that the main features exciting the DCNN nodes are a decreased power in the alpha band and an increased power in the delta-theta band around 100ms for ADHD patients compared to HC, suggestive of attentional and inhibition deficits, which have been previously suggested as pathophyisiological signatures of ADHD. While confirmation with larger clinical samples is necessary, these results highlight the potential of this methodology to develop CNS biomarkers of practical clinical utility.", "URL": "https://doi.org/10.1101/19005611"} |
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] | {"Title": "Predicting Under-five mortality across 21 Low and Middle-Income Countries using Deep Learning Methods", "Authors": "Adegbosin Adeyinka E, Stantic Bela, Sun Jing", "Abstract": "Abstract Objectives To explore the efficacy of Machine Learning (ML) techniques in predicting under-five mortality in LMICs and to identify significant predictors of under-five mortality (U5M). Design This is a cross-sectional, proof-of-concept study. Settings and participants We analysed data from the Demographic and Health Survey (DHS). The data was drawn from 21 Low-and-Middle Income Countries (LMICs) countries (N = 1,048,575). Eligible mothers in each household were asked information about their children and the reproductive care they received during the pregnancy. Primary and secondary outcome measures The primary outcome measure was under-five mortality; secondary outcome was comparing the efficacy of deep learning algorithms: Deep Neural Network (DNN); Convolution Neural Network (CNN); Hybrid CNN-DNN with Logistic Regression (LR) for the prediction of child survival. Results We found that duration of breast feeding, household wealth index and the level of maternal education are the most important predictors of under-five mortality. We found that deep learning techniques are superior to LR for the classification of child survival: LR sensitivity = 0.47, specificity = 0.53; DNN sensitivity = 0.69, specificity = 0.83; CNN sensitivity = 0.68, specificity = 0.83; CNN-DNN sensitivity = 0.71, specificity = 0.83. Conclusion Our findings provide an understanding of interventions that needs to be prioritized, in order to reduce levels of U5M in LMICs. It also demonstrates that deep learning models are more efficacious than a traditional analytical approach. Strengths and limitations of this study The models were tested using a very large data sample, drawn from over 1 million households. The survey utilised a cluster sampling approach and are representative of each country included. Socio-economic, political and cultural differences between the included countries may limit generalisability of the results. The cross-sectional design of the study means we can only infer association and not causality.", "URL": "https://doi.org/10.1101/19007583"} |
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] | {"Title": "White adipose tissue inflammation is not attenuated by short-term calorie restriction in obese humans", "Authors": "Sbierski-Kind Julia, Mai Knut, Kath Jonas, Jurisch Anke, Streitz Mathias, Kuchenbecker Leon, J\u00fcrchott Karsten, Spranger Leonard, von Schwartzenberg Reiner Jumpertz, Decker Anne-Marie, Kr\u00fcger Ulrike, Volk Hans-Dieter, Spranger Joachim", "Abstract": "Abstract Obesity is a growing global health problem due to its association with chronic low-grade inflammation contributing to metabolic complications. Multiple studies indicate that white adipose tissue (WAT) inflammation can promote type 2 diabetes. However, the function and regulation of both innate and adaptive immune cells in human WAT under conditions of obesity and calorie restriction (CR) is not fully understood yet. Using a randomized interventional design, we investigated postmenopausal obese women who either underwent CR for three months followed by a 4 weeks phase of weight maintenance or had to maintain a stable weight over the whole study period. A comprehensive immune phenotyping protocol was conducted using validated multiparameter flow cytometry analysis in blood and subcutaneous WAT (SAT) (n=21). The T cell receptor repertoire was analyzed by next generation sequencing (n=20) and cytokine levels were determined in SAT (n=22). Metabolic parameters were determined by hyperinsulinemic-euglycemic clamp and then correlated to immune cell subsets. We found that insulin resistance (IR) correlates significantly with a shift towards the memory T cell compartment in SAT. Among various T cell subsets, predominantly CD8 + effector memory T cells were associated with obesity-related IR. Interestingly, T cell receptor analysis revealed a diverse repertoire in SAT arguing against an antigen-driven intra-SAT expansion of effector memory T cells. Surprisingly, neither inflammatory cytokine levels nor leucocyte subpopulations were significantly altered upon CR. Our findings demonstrate the accumulation of effector memory T cells in obese SAT contributing to chronic inflammation. The long-standing effect of obesity-induced changes in SAT was demonstrated by preserved immune cell composition after short-term CR induced weight loss.", "URL": "https://doi.org/10.1101/19005934"} |