bluuebunny/crossref_metadata_2025 huggingface dataset:
Dural Arteriovenous Fistulas Presenting as Symmetric Lesions in the Internal Capsule on Imaging Studies
Authors: Zhang Daihui , Liang Kuopeng , Yin Juntao , Tang Lingtao , Yang Xiaoyi , Yang Zhihong , Li Xingliang
Published: May 2023

Background:

Dural arteriovenous fistulas (DAVFs) leading to oedema, primarily in the internal capsule, are extremely rare and, to our knowledge, have never been reported. We reported a case of DAVFs with oedema in bilateral internal capsule oedema and reviewed the literature.

Methods:

The report describes a unique imaging presentation of cases of DAVFs as symmetric lesions, mainly in the bilateral internal capsule. It also reviews the literature for symmetric lesions in the internal capsule and central grey matter caused by DAVFs to further characterize this rare entity and differential diagnosis through imaging features.

Results:

In cases of symmetric oedema caused by DAVFs, the most common artery involved in arterial supply was the middle meningeal artery (13/24; 54%). The main vein involved in the drainage was the Galen vein (18/29; 62%). Most cases were treated with transarterial embolization (23/29; 79%), and the probability of effective treatment or complete cure is 100%. On imaging, the vasogenic oedema signal caused by DAVFs is a symmetrical lesion of the bilateral internal capsule, that is, DWI MRI shows a high signal in the unrestricted diffusion area on the apparent diffusion coefficient map.

Conclusions:

MR has good diagnostic value in abnormal basal ganglia symmetric signals caused by DAVFs, and can quickly identify DAVFs early.
Frontal Hypoperfusion and Cerebellar Hyperperfusion in Transient Alcoholic Cerebellar Degeneration
Authors: Chuang Tzyy-Ling , Wang Yuh-Feng
Published: May 2023

A 55-year-old man consumed approximately 10 units of alcohol daily for 25 years, developing social withdrawal after retiring. For 2 months, he walked diagonally to the right, with a right shoulder droop. He spoke and walked slowly, but his speech was clear. After 20 days of abstinence, his symptoms improved, and his walk became more steady. Brain MRI revealed no specific finding. Brain perfusion scintigraphy with 99mTc-ECD on 2-tailed view display in eZIS showed hypoperfusion in the prefrontal, frontal, and left anterior temporal lobes and left thalamus and hyperperfusion in the posterior white matter, parietal-occipital cortical regions, pons, and cerebellum.
Subciliary Rotating Sutures Combined With Modified Hotz Procedure for Correction of Congenital Lower Eyelid Entropion
Authors: Khuu Thomas H. , Czyz Craig N. , Michels Kevin S.
Published: May 2023

Purpose

Standard techniques for the treatment of congenital lower eyelid entropion may not yield suitable outcomes or may result in overcorrection if disinsertion of the lower eyelid retractors is not the primary cause. Herein, we propose and evaluate a technique using subciliary rotating sutures combined with a modified Hotz procedure for repair of lower eyelid congenital entropion that addresses these concerns.

Methods

A retrospective chart review was conducted of all patients who underwent lower eyelid congenital entropion repair by a single surgeon using subciliary rotating sutures combined with a modified Hotz procedure between 2016 and 2020. Study variables included patient demographics, follow-up period, postoperative complications, operative success, and recurrence.

Results

Twelve patients (19 eyelids) met the study inclusion criteria. The mean patient age was 7.1 ± 6.1 years (range, 0.2–22 years). Nine of the patients were female (75%) and 3 were male (25%). The distribution of eyelids was 8 right (42%) and 11 left (58%). The mean follow-up time was 19.5 ± 15 (range 2.5–45) months. There were two eyelids (11%) that had entropion recurrence after initial repair in patients with concomitant compound disease processes. Repeated repair resulted in success with no recurrence at last follow-up. Overall, the described entropion repair technique was successful and without recurrence in 17 eyelids (89%). There were no cases of ectropion, lid retraction, or other complications.

Conclusions

Subciliary rotating sutures combined with a modified Hotz procedure are effective for correction of congenital lower eyelid entropion. As the technique does not manipulate the posterior layer of the lower eyelid retractors, it may be useful for when retractor reinsertion does not yield adequate improvement and may also reduce the risk of eyelid retraction and overcorrection in particular cases.
Supported Intervention Versus Intervention Alone for Management of Fecal Incontinence in Patients With Inflammatory Bowel Disease
Authors: Dibley* Lesley , Hart Ailsa , Duncan* Julie , Knowles Charles H. , Kerry Sally , Lanz* Doris , Berdunov* Vladislav , Madurasinghe* Vichithranie W. , Wade Tiffany , Terry Helen , Verjee Azmina , Fader Mandy , Norton Christine
Published: May 2023

PURPOSE:

The aims of this study were to test a noninvasive self-management intervention supported by specialist nurses versus intervention alone in patients with inflammatory bowel disease (IBD) experiencing fecal incontinence and to conduct a qualitative evaluation of the trial.

DESIGN:

Multicenter, parallel-group, open-label, mixed-methods randomized controlled trial (RCT).

SUBJECTS AND SETTING:

The sample comprised patients from a preceding case-finding study who reported fecal incontinence and met study requirements; the RCT was delivered via IBD outpatient clinics in 6 hospitals (5 in major UK cities, 1 rural) between September 2015 and August 2017. Sixteen participants and 11 staff members were interviewed for qualitative evaluation.

METHODS:

Adults with IBD completed the study activities over a 3-month period following randomization. Each participant received either four 30-minute structured sessions with an IBD clinical nurse specialist and a self-management booklet or the booklet alone. Low retention numbers precluded statistical analysis; individual face-to-face or telephone interviews, recorded digitally and transcribed professionally, were conducted to evaluate the RCT. Transcripts were analyzed thematically using an inductive method.

RESULTS:

Sixty-seven participants (36%) of the targeted 186 participants were recruited. The groups comprised 32 participants (17% of targeted participants) allocated to the nurse + booklet intervention and 35 (18.8% of targeted participants) allocated to the booklet alone. Less than one-third (n = 21, 31.3%) completed the study. Given the low recruitment and high attrition, statistical analysis of quantitative data was considered futile. Participant interviews were conducted concerning study participation and 4 themes emerged that described experiences of patients and staff. These data provided insights into reasons for low recruitment and high attrition, as well as challenges of delivering resource-heavy studies in busy health service environments.

CONCLUSIONS:

Alternative approaches to trials of nurse-led interventions in hospital settings are needed as many interfering factors may prevent successful completion.
Management of Localized Small- and Large-Cell Pancreatic Neuroendocrine Carcinoma in the National Cancer Database
Authors: Sugawara Toshitaka , Rodriguez Franco Salvador , Franklin Oskar , Kirsch Michael J , Colborn Kathryn L , Del Chiaro Marco , Schulick Richard D
Published: May 2023

BACKGROUND:

The role of curative-intent resection and perioperative chemotherapy for nonmetastatic pancreatic neuroendocrine carcinoma (PanNEC) remains unclear due to their biological aggressiveness and rarity. This study aimed to evaluate the association of resection and perioperative chemotherapy with overall survival for nonmetastatic PanNEC.

STUDY DESIGN:

Patients with localized (cT1–3, M0), small- and large-cell PanNEC were identified in the National Cancer Database from 2004 to 2017. The changing trends in terms of the annual proportions of resection and adjuvant chemotherapy were assessed. The survival of patients who received resection and those who received adjuvant chemotherapy were investigated using Kaplan–Meier estimates and Cox regression models.

RESULTS:

In total, 199 patients with localized small- and large-cell PanNEC were identified; 50.3% of those were resected, and 45.0% of the resected patients received adjuvant chemotherapy. Rate of resection and adjuvant treatment has trended upward since 2011. The resected group was younger, was more often treated at academic institutions, had more distal tumors, and had a lower number of small-cell PanNEC. The median overall survival was longer in the resected group compared to the unresected group (29.4 months vs 8.6 months, p < 0.001). Resection was associated with improved survival in a multivariable Cox regression model adjusting for preoperative factors (adjusted hazard ratio 0.58, 95% CI 0.37 to 0.92), while adjuvant therapy was not.

CONCLUSIONS:

This nationwide retrospective study suggests that resection is associated with improved survival in patients with localized PanNEC. The role of adjuvant chemotherapy needs more investigation.
Correlation of Performance on ENTRUST and Traditional Oral Objective Structured Clinical Examination for High-Stakes Assessment in the College of Surgeons of East, Central, and Southern Africa
Authors: Liebert Cara A , Melcer Edward F , Eddington Hyrum , Trickey Amber , Shields Samuel , Lee Melissa , Korndorffer James R , Bekele Abebe , Wren Sherry M , Lin Dana T
Published: May 2023

Background:

To address the global need for accessible evidence-based tools for competency-based education, we developed ENTRUST, an innovative online virtual patient simulation platform to author and securely deploy case scenarios to assess surgical decision-making competence.

Study Design:

In partnership with COSECSA, ENTRUST was piloted during the Membership of the College of Surgeons (MCS) 2021 examination. Examinees (n=110) completed the traditional 11-station oral OSCE, followed by three ENTRUST cases, authored to query similar clinical content of three corresponding OSCE cases. ENTRUST scores were analyzed for associations with MCS Exam outcome using independent sample t-tests. Correlation of ENTRUST scores to MCS Exam Percentage and OSCE Station Scores were calculated with Pearson correlations. Bivariate and multivariate analyses were performed to evaluate predictors of performance.

Results:

ENTRUST performance was significantly higher in examinees who passed the MCS Exam compared to those who failed (p<0.001). ENTRUST score was positively correlated with MCS Exam Percentage (p<0.001) and combined OSCE Station Scores (p<0.001). On multivariate analysis, there was a strong association between MCS Exam Percentage and ENTRUST Grand Total Score (p<0.001), Simulation Total Score (p=0.018), and Question Total Score (p<0.001). Age was a negative predictor for ENTRUST Grand Total and Simulation Total Score, but not for Question Total Score. Sex, native language status, and intended specialty were not associated with performance on ENTRUST.

Conclusion:

This study demonstrates feasibility and initial validity evidence for the use of ENTRUST in a high-stakes examination context for assessment of surgical decision-making. ENTRUST holds potential as an accessible learning and assessment platform for surgical trainees worldwide.
Alcohol Use among Emergency Medicine Department Patients in Tanzania: A Comparative Analysis of Injury Versus Non-Injury Patients
Authors: Pauley Alena , Thatcher Emily C. , Sarafian Joshua T. , Zadey Siddhesh , Shayo Frida , Mmbaga Blandina T. , Sakita Francis , Boshe Judith , Vissoci João Ricardo Nickenig , Staton Catherine A.
Published: May 2023

Background

Alcohol is a leading behavioral risk factor for death and disability worldwide. Tanzania has few trained personnel and resources for treating unhealthy alcohol use. In Emergency Medicine Departments (EMDs), alcohol is a well-known risk factor for injury patients. At Kilimanjaro Christian Medical Center (KCMC) in Moshi, Tanzania, 30% of EMD injury patients (IP) test positive for alcohol upon arrival to the ED. While the IP population is prime for EMD-based interventions, there is limited data on if non-injury patients (NIP) have similar alcohol use behavior and potentially benefit from screening and intervention as well.

Methods

This was a secondary analysis of a systematic random sampling of adult (≥18 years old), KiSwahili speaking, KCMC EMD patients surveyed between October 2021 and May 2022. When medically stable and clinically sober, participants provided informed consent. Information on demographics (sex, age, years of education, type of employment, income, marital status, tribe, and religion), injury status, self-reported alcohol use, and Alcohol Use Disorder (AUD) Identification Test (AUDIT) scores were collected. Descriptive statistics were analyzed in Rstudio using frequencies and proportions.

Results

Of the 376 patients enrolled, 59 (15.7%) presented with an injury. The IP and NIP groups did not differ in any demographics except sex, an expected difference as females were intentionally oversampled in the original study design. The mean [SD] AUDIT score (IP: 5.8 [6.6]; NIP: 3.9 [6.1]), drinks per week, and proportion of AUDIT ≥8 was higher for IP (IP:37%; NIP: 21%). However, alcohol preferences, drinking quantity, weekly expenditure on alcohol, perceptions of unhealthy alcohol use, attempts and reasons to quit, and treatment seeking were comparable between IPs and NIPs.

Conclusion

Our data suggests 37% of injury and 20% of non-injury patients screen positive for harmful or hazardous drinking in our setting. An EMD-based alcohol treatment and referral process could be beneficial to reduce this growing behavioral risk factor in non-injury as well as injury populations.
Integrated NMR and MS analysis of plasma metabolome reveals major changes in inflammatory markers, one-carbon, lipid, and amino acid metabolism in severe and fatal COVID-19 subjects
Authors: Gama-Almeida Marcos C. , Teixeira Lívia , Hottz Eugenio D. , Ivens Paula , Ribeiro Hygor , Pinto Gabriela D. A. , Garrett Rafael , Torres Alexandre G. , Carneiro Talita I. A. , Barbalho Bianca de O , Ludwig Christian , Struchiner Claudio J. , Assunção-Miranda Iranaia , Valente Ana Paula C. , Bozza Fernando A. , Bozza Patrícia T. , dos Santos Gilson C. , El-Bacha Tatiana
Published: May 2023

Brazil has the second highest COVID-19 death rate while Rio de Janeiro is among the states with the highest rate in the country. Although effective vaccines have been developed, it is anticipated that the ongoing COVID-19 pandemic will transition into an endemic state. Under this scenario, it is worrisome that the underlying molecular mechanisms associated with the disease clinical evolution from mild to severe, as well as the mechanisms leading to long COVID are not yet fully understood. In this study,1H Nuclear Magnetic Resonance spectroscopy and Liquid Chromatography-Mass spectrometry-based metabolomics were used to identify potential pathways and metabolites involved in COVID-19 pathophysiology and disease outcome. We prospectively enrolled 35 severe RT-PCR confirmed COVID-19 cases within 72 hours from intensive care unit admission, between April and July 2020 from two reference centers in Rio de Janeiro, and 12 samples from non-infected control subjects. Of the 35 samples from COVID-19 patients, 18 were from survivors and 17 from non-survivors. We observed that patients with severe COVID-19 had their plasma metabolome significantly changed if compared to control subjects. We observed lower levels of glycerophosphocholine and other choline-related metabolites, serine, glycine, and betaine, indicating a dysregulation in methyl donors and one-carbon metabolism. Importantly, non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid andN-acetylserine compared to survivors and controls, reflecting uncontrolled inflammation, liver and kidney dysfunction, and insulin resistance in these patients. Lipoprotein dynamics and amino acid metabolism were also altered in severe COVID-19 subjects. Several changes were greater in women, thus patient’s sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. The incidence of severe outcome after hospital discharge is very high in Brazil, thus these metabolic alterations may be used to monitor patients’ organs and tissues and to understand the pathophysiology of long-post COVID-19.
Prognostic value of flow-mediated dilation and computed tomography angiography findings for determining cardiovascular risk in patients with subclinical atherosclerosis
Authors: Kawai Hideki , Sarai Masayoshi , Sugimoto Kunihiko , Motoyama Sadako , Sato Yoshihiro , Nagahara Yasuomi , Miyajima Keiichi , Matsuyama Takahiro , Takahashi Hiroshi , Yamada Akira , Naruse Hiroyuki , Toyama Hiroshi , Ozaki Yukio , Izawa Hideo
Published: May 2023

Background

Flow-mediated dilation (FMD) tests endothelial function, and computed tomography angiography (CTA) estimates the extent of coronary atherosclerosis and plaque vulnerability. This study aimed to examine the prognostic value of combining FMD and CTA in patients with no history of atherosclerotic disease.

Methods

The study retrospectively examined patients who underwent CTA and FMD within 3 months between 2012 and 2020. Patients with a history of cardio-cerebrovascular disease or significant stenoses on CTA were excluded. The study endpoint was defined as major cardiac and cerebrovascular events (MACCE): a composite of cardio-cerebrovascular death, acute coronary syndrome, fatal arrhythmia, ischaemic and haemorrhagic stroke, and late revascularisation of the coronary or carotid arteries 6 months after CTA. Finally, the patients were stratified into four groups based on the following factors: FMD <6.0%, per cent atheroma volume (PAV) ≥21.0%, and the presence of high-risk plaques (HRPs).

Results

During a mean follow-up of 4.7 years, MACCE occurred in 19 of 154 patients (mean age: 61.0±12.9 years, 89 males). FMD, PAV, and HRPs were independent predictors of MACCE after adjusting for age, sex, and hypertension. Compared with the patients with 0 points, hazard ratios of those with 1, 2, and 3 points were 2.76 (P=0.322), 9.89 (P=0.004), and 28.43 (P<0.001), respectively. Adding FMD, PAV, and HRPs to the baseline model, including age, sex, and hypertension, improved the C-index (0.712–0.831, P=0.023).

Conclusions

Although FMD and CTA findings are useful for predicting cardiovascular events, their combination synergises their prognostic abilities.
Associations between rheumatoid arthritis clinical factors with synovial cell types and states
Authors: Weisenfeld Dana , Zhang Fan , Donlin Laura , Jonsson Anna Helena , Apruzzese William , Campbell Debbie ,   Accelerating Medicines Partnership Program: Rheumatoid Arthritis Network, Holers V. Michael , Gravallese Ellen , Moreland Larry , Goodman Susan , Brenner Michael , Raychaudhuri Soumya , Filer Andrew , Anolik Jennifer , Bykerk Vivian , Liao Katherine P.
Published: May 2023

Objective

Recent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium.

Methods

The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited subjects with active RA on no DMARDs or inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint and tissue disaggregated and processed with a CITE-seq pipeline from which cell type percentages and cell type abundance phenotypes (CTAP) were derived: endothelial/fibroblast/myeloid (EFM), fibroblasts (F), myeloid (M), T/B cells (TB), T cells/fibroblasts (TF), T/myeloid cells (TM). Correlations were measured between RA clinical factors, % cell type, and CTAPs.

Results

We studied 72 subjects, mean age 57 years, 75% female, 83% seropositive, mean RA duration 6.6 years, mean DAS28-CRP3 4.8. Higher DAS28-CRP3 correlated with higher % T cells (p<0.01). Subjects on MTX not on bDMARD had higher %B cells vs no DMARDs (p<0.01). The majority of subjects on bDMARDs were categorized as EFM (57%), while none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, DAS28-CRP3.

Conclusion

In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors may impact cell type/state in the synovium and ultimately response to subsequent therapies.
Researching COVID to enhance recovery (RECOVER) autopsy tissue pathology study protocol: Rationale, objectives, and design
Authors: Troxel Andrea B. , Bind Marie-Abele C. , Flotte Thomas J. , Cordon-Cardo Carlos , Decker Lauren A. , Finn Aloke V. , Padera Robert F. , Reichard R. Ross , Stone James R. , Adolphi Natalie L. , Casimero Faye Victoria C. , Crary John F. , Elifritz Jamie , Faustin Arline , Ghosh Saikat Kumar B. , Krausert Amanda , Martinez-Lage Maria , Melamed Jonathan , Mitchell Roger A. , Sampson Barbara A. , Seifert Alan C. , Simsir Aylin , Adams Cheryle , Haasnoot Stephanie , Hafner Stephanie , Siciliano Michelle A. , Vallejos Brittany B. , Boccio Phoebe Del , Lamendola-Essel Michelle F. , Young Chloe E. , Kewlani Deepshikha , Akinbo Precious A. , Parent Brendan , Chung Alicia , Cato Teresa C. , Mudumbi Praveen C. , Esquenazi-Karonika Shari , Wood Marion J. , Chan James , Monteiro Jonathan , Shinnick Daniel J. , Thaweethai Tanayott , Nguyen Amber N. , Fitzgerald Megan L. , Perlowski Alice A. , Stiles Lauren E. , Paskett Moira L. , Katz Stuart D. , Foulkes Andrea S.
Published: May 2023

Importance

SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Tissue Pathology Study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.

Methods

RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Casual inference methods will be employed to investigate associations between risk factors and pathologic outcomes.

Discussion

RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.

Clinicaltrials.govnumber:NCT05292274
Classifying Glaucoma Using Machine Learning Techniques
Authors: Santos Dheiver Francisco
Published: May 2023

Glaucoma is a common eye disease that can lead to blindness if not detected and treated early. In this paper, we present a machine learning-based approach for classifying glaucoma. We use a publicly available dataset of retinal images and extract features using convolutional neural networks. We compare the performance of different classifiers, including random forest, support vector machine, and XGBoost, and evaluate their accuracy, precision, recall, and F1 score. Our results show that the XGBoost classifier achieves the highest accuracy and F1 score, indicating its potential for diagnosing glaucoma in clinical practice.
Improving patient flow through hospitals with machine learning based discharge prediction
Authors: Wei Jia , Zhou Jiandong , Zhang Zizheng , Yuan Kevin , Gu Qingze , Luk Augustine , Brent Andrew J , Clifton David A. , Walker A. Sarah , Eyre David W.
Published: May 2023

Accurate predictions of hospital discharge events could help improve patient flow through hospitals and the efficiency of care delivery. However, the potential of integrating machine learning with diverse electronic health records (EHR) data for this task has not been fully explored. We used EHR data from 01 February 2017 to 31 January 2020 in Oxfordshire, UK to predict hospital discharges in the next 24 hours. We fitted separate extreme gradient boosting models for elective and emergency admissions, trained using the first two years of data and tested using the final year of data. We examined individual-level and hospital-level model performance and evaluated the impact of training data size and recency, prediction time of day, and performance in different subgroups. Our individual patient level models for elective and emergency admissions achieved AUCs of 0.87 and 0.86, AUPRCs of 0.66 and 0.64 and F1 scores of 0.61 and 0.59, respectively, substantially better than a baseline logistic regression model. Aggregating individual probabilities, the total daily number of hospital discharges could also be accurately estimated, with mean absolute errors of 8.9% (elective admissions) and 4.9% (emergency admissions). The most informative predictors included antibiotic prescriptions, other medications, and hospital capacity factors. Performance was generally robust across patient subgroups and different training strategies, but lower in patients with longer lengths of stay and those who eventually died in hospital. Our findings highlight the potential of machine learning in optimising hospital patient flow and facilitating patient care and recovery.
Quantile regressions as a tool to evaluate how an exposure shifts and reshapes the outcome distribution: A primer for epidemiologists
Authors: Khadka Aayush , Hebert Jillian , Maria Glymour M. , Jiang Fei , Irish Amanda , Duchowny Kate , Vable Anusha M.
Published: May 2023

Most regression models estimate an exposure’s association with the mean value of the outcome, but quantifying how an exposure affects the entire outcome distribution is often important (e.g., when the outcome has non-linear relationships with risk of other adverse outcomes). Quantile regressions offer a powerful way of estimating an exposure’s relationship with the outcome distribution but remain underused in epidemiology. We introduce quantile regressions and then present an empirical example in which we fit mean and quantile regressions to investigate the association of educational attainment with later-life systolic blood pressure (SBP). We use data on 8,875 US-born respondents aged 50+ years from the Health and Retirement Study. More education was negatively associated with mean SBP. Conditional and unconditional quantile regressions both suggested a negative association between education and SBP at all levels of SBP, but the absolute magnitudes of these associations were higher at higher SBP quantiles relative to lower quantiles. While all estimators showed more education was associated with a leftward shift of the SBP distribution, quantile regression results additionally revealed that education may have reshaped the SBP distribution through larger protective associations in the right tail, thus benefiting those at highest risk of cardiovascular diseases.
Oral anticoagulation in heart failure complicated by atrial fibrillation: Outcomes in routine data
Authors: Möckel Martin , Pudasaini Samipa , Baberg Henning Thomas , Levenson Benny , Malzahn Jürgen , Mansky Thomas , Michels Guido , Günster Christian , Jeschke Elke
Published: May 2023

Background

Aim of this study was to test if oral anticoagulant (OAC) use in patients with heart failure (HF), accompanied by atrial fibrillation (AF), leads to a favorable outcome. Further, the specific impact of non-vitamin K oral anticoagulants (NOACs) is analyzed.

Methods

Anonymous data from all patients with a health insurance at the largest entity which covers approximately 30% of the German population. Patients with a claims record for hospitalization with the main diagnosis of HF and AF from the years 2017 to 2019 were included. A hospital stay in the previous year was an exclusion criterion. Mortality and readmission for all-cause and stroke/intracranial bleeding (ICB) were analyzed 91-365 days after the index hospitalization. Kaplan-Meier survival curves and multivariable Cox regression models were used to evaluate the impact of medication on outcome.

Results

180,316 cases were included [81 years (IQR 76 to 86), 55.6% female, CHA2DS2-VASc score ≥ 2 (96.81%)]. In 80.6%, OACs were prescribed (vitamin K antagonists (VKA): 21.7%; direct factor Xa inhibitors (FXaI): 60.0%; direct thrombin inhibitors (DTI): 3.4%; with multiple prescriptions per patient included). The mortality rate was 19.1%, readmission rate was 29.9% and stroke/ICB occurred in 1.9%. Risk of death was lower with the any OAC (HR 0.77, 95% CI 0.75 to 0.79) but without significant differences in OAC type (VKA: HR 0.73, 95% CI 0.71 to 0.76; FXaI: HR 0.77, 95% CI 0.75 to 0.78; DTI: HR 0.71, 95% CI 0.66 to 0.77). The total readmission rate (HR 0.97, 95% CI 0.94 to 0.99) and readmission for stroke/ICB (HR 0.71, 95% CI 0.65 to 0.77) was lower with OAC.

Conclusions

Routine data confirm the positive effect of OACs in HF-AF. There are no additional benefits regarding mortality with the use of NOACs.

Clinical Perspective

What is new?

This routine data analysis on a study population of 180,316 indicates a decreasing mortality rate, 91 to 365 days after index hospital stay, in patients with HF complicated by AF in case oral anticoagulants (OACs) were prescribed.

Secondly, the findings imply no additional benefits of new OACs (NOACs) compared to vitamin K antagonists.

What are the clinical implications?

Our study highlights the benefits of a permanent oral anticoagulation therapy in patients with heart failure (HF) complicated by atrial fibrillation (AF).

For patients with HF and AF, the results indicate room for personalizationin choosing the specific OAC type for anticoagulation as NOACs show no survival benefit over vitamin K antagonists.
Population-based surveillance of drug-resistant tuberculosis in Southern Mozambique based on whole genome sequencing
Authors: Mariner-Llicer Carla , Cervera Belén Saavedra , Mambuque Edson , Munguambe Shilzia , Gomes Neide , Villamayor Luis , Cancino-Muñoz Irving , Torres-Puente Manuela , Nguenha Dinis , Respeito Durval , Tembe Gustavo , López Mariana G. , Comas Iñaki , García-Basteiro Alberto L.
Published: May 2023

Mozambique is considered a high multidrug-resistant (MDR-TB) country by the World Health Organization (WHO) (3.7% new MDR-TB cases). The last national WHO survey was performed in 2008. Nowadays, South Africa and Eswatini are reporting an increase in MDR-TB cases heightened, in Eswatini, by the spread of a MDR-TB strain harbouring therpoB_I491F mutation not detected by XpertUltra/RIF. Due to the concerning MDR-TB situation in its neighbouring countries, it is crucial to review the current resistance status in Mozambique. Our aim is to depict the current prevalence of drug-resistance to first and second-line drugs and track its trends since 2008. We analysed 312Mycobacterium tuberculosisgenomes from a population-based survey conducted in Manhiça in 2018 and looked for drug-resistance mutations included in the recently published WHO catalogue and compared with the prevalences reported in 2014 and 2008. We found that the overall resistance increased in 2014 (15.9%) and 2018 (14.4%) was slightly higher than the one reported in 2008. Although, new multidrug/rifampicin resistance cases remained consistent with the 2008 prevalence study (3.5%) indicating that MDR-TB is not spreading as rapidly as in neighbouring countries. Importantly, we detected a high isoniazid (INH) prevalence not associated with MDR-TB (4.2%, 5.5% and 7.6% in 2008, 2014 and 2018, p-value=0.03) suggesting that a sizeable number of cases are INH-resistant before starting treatment and not detected by XpertUltra/RIF. Fortunately, no mutations associated with second-line drug-resistance were found in the dataset. Our results show a stable drug-resistance situation in Manhiça with the need to monitor isoniazid resistance, and highlight the potential of WGS to be used in national surveys to expand our knowledge of drug-resistance prevalence throughout all Mozambican provinces.
Profiling small RNAs in CRC screening samples such as the widely used fecal immunochemical test, is it possible?
Authors: Birkeland Einar , Ferrero Giulio , Pardini Barbara , Umu Sinan U. , Tarallo Sonia , Bulfamante Sara , Hoff Geir , Senore Carlo , Rounge Trine B , Naccarati Alessio
Published: May 2023

Faecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers for their stability and detectability. Colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of the FIT leftover buffer, would be ideal due to its widespread use.

In the present study, we applied small RNA sequencing to FIT leftover samples collected from two European screening populations. We showed robust detection of miRNA and microbial profiles, which were similar to those obtained from specimens sampled using RNA stabilising buffers and archived fecal samples. Detected miRNAs exhibited differential abundance between CRC and control samples that was consistent between sampling methods, suggesting a promising potential to identify small RNA CRC biomarkers using FIT leftovers. We demonstrated that it is possible to analyse gut miRNAs in FIT leftover samples and envision that these potential biomarkers can complement the FIT in large scale screening settings.
Duration and Frequency Mismatch Negativity in Schizophrenia, unaffected first-degree relatives, and healthy controls
Authors: Bose Anushree , Agarwal Sri Mahavir , Nawani Hema , Shivakumar Venkataram , Sreeraj Vanteemar S. , Narayanaswamy Janardhanan C. , Kumar Devvarta , Venkatasubramanian Ganesan
Published: May 2023

Background

Mismatch negativity (MMN) is elicited upon detecting background irregularities in the sensory environment and subsequent updating of the sensory context. Auditory MMN amplitude is reliably attenuated in schizophrenia patients. However, due to diversity in MMN deviant types (duration, frequency, intensity, gap, etc.), considerable variability exists in MMN findings reported from the early course and chronic samples. MMN is sometimes reported to be impaired or associated with schizotypy, but MMN and schizotypy are yet to be well examined in unaffected first-degree relatives of schizophrenia patients.

Methods

Fifty-two schizophrenia patients (SZ) were compared with thirty-six unaffected first-degree relatives (FDR) of schizophrenia patients and thirty-two age and sex-matched healthy controls (HC) on MMN indices using a two-tone passive auditory oddball paradigm with two conditions – duration deviant (MMNd) and frequency deviant (MMNf) event-related potential experiment. SZ sample was further split into two sub-groups 1) early-course/drug-naïve or drug-free (dSZ), and 2) chronic/medicated (cSZ) to examine the effect of illness chronicity and medication on MMN indices. We also checked whether schizotypy scores associated with MMNd and MMNf amplitudes in the FDR group.

Results

At baseline, SZ group had significantly diminished MMNd amplitude compared to both HC and FDR groups (p<0.001). The SZ group also had significantly lower MMNd latency than the FDR group (p<0.014). The cSZ and dSZ groups did not differ from each other on MMN amplitude or latency, though cSZ group had lower MMN amplitude. Only cSZ patients showed negative correlation of MMNd amplitude with hallucinations scores and total duration of illness. In FDRs, MMNd and MMNf amplitudes showed negative correlation with the cognitive-perceptual factor of schizotypy.

Discussion

Deficient MMNd in SZ patients adds further support to the prediction error estimation abnormalities in schizophrenia. MMNd is a more robust measure than MMNf in differentiating SZ from FDR and HC. MMNd amplitude could be more impaired in hallucinating SZ patients and associate with illness chronicity. Though unaffected FDRs have MMN comparable to healthy controls, higher schizotypy in FDR is associated with lower MMN amplitude. MMN and schizotypy are potentially linked and deserve a nuanced examination.
Comprehensive Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome
Authors: Tisza Michael , Cregeen Sara Javornik , Avadhanula Vasanthi , Zhang Ping , Ayvaz Tulin , Feliz Karen , Hoffman Kristi L. , Clark Justin R. , Terwilliger Austen , Ross Matthew C. , Cormier Juwan , Henke David , Troisi Catherine , Wu Fuqing , Rios Janelle , Deegan Jennifer , Hansen Blake , Balliew John , Gitter Anna , Zhang Kehe , Li Runze , Bauer Cici X. , Mena Kristina D. , Piedra Pedro A. , Petrosino Joseph F. , Boerwinkle Eric , Maresso Anthony W.
Published: May 2023

Wastewater is a discarded human by-product but analyzing it may help us understand the health of communities. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. We conducted a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Over 450 distinct pathogenic viruses were detected. Sequencing reads of established pathogens and emerging viruses correlated to clinical data sets. Viral communities were tightly organized by space and time. Finally, the most abundant human viruses yielded sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.

One-Sentence Summary

Wastewater contains a trickle of circulating human viruses, and now we can sequence them to better track community transmission.
Percutaneous coronary intervention has better in-hospital outcomes in severe renal failure patients
Authors: Li Renxi , Luo Qianyun
Published: May 2023

Background

In patients with severe renal failure, coronary artery bypass surgery (CABG) was found to have better long-term outcomes than percutaneous coronary intervention (PCI). This study aims to provide a retrospective analysis of short-term in-hospital peri-operative outcomes between PCI and CABG in patients with severe renal failure.

Methods

Patients who underwent CABG and PCI in Q4 2015-2020 were identified in National Inpatient Sample (NIS) database. Patients of age<40 were excluded for congenital heart defects. Patients with comorbidity of severe renal failure were included. Between patients undergoing PCI and CABG, preoperative variables were compared and corrected in multivariable logistic regression examining their in-hospital peri-operative outcomes. Adjusted odds ratios (aOR) were estimated for mortality and morbidities.

Results

In NIS, 4,512 CABG and 13,242 PCI cases were identified. Compared to CABG, patients who underwent PCI had lower mortality (4.24% vs 5.47%, aOR 0.725, p<0.0001) and lower morbidity including heart failure (0.14% vs 2.97%, aOR 0.044, p<0.0001), stroke (0.12% vs 0.47%, aOR 0.264, p<0.0001), respiratory complications (0.51% vs 7.34%, aOR 0.063, p<0.0001), renal complications (0.05% vs 0.49%, aOR 0.075, p<0.0001), acute kidney injury (8.67% vs 12.66%, aOR 0.646, p<0.0001), deep wound complications (0.02% vs 0.35%, aOR 0.042, p < 0.0001), shock (0.22% vs 0.95%, aOR 0.228, p<0.0001), and length of in-hospital stay over 7 days (24.75% vs 73.52%, aOR 0.106, p<0.0001).

Conclusion

NIS is a comprehensive database of nationwide providers, providing robust power in analysis. In patients with severe renal failure, PCI offers an advantage over CABG in terms of short-term in-hospital perioperative outcomes.
Development and Validation of Comorbidity Index to Predict In-hospital Mortality Risk for Patients with Steven-Johnson Syndrome
Authors: Li Renxi
Published: May 2023

Background

Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) is a spectrum of severe drug reactions that has a high in-hospital mortality from 5% to 20%. Early risk prediction for in-hospital mortality in SJS/TEN can be informative for clinical management. This study aimed to develop an in-hospital mortality risk calculator for SJS based on patient comorbidities.

Methods

Patients who were diagnosed with SJS/TEN were identified in the National Inpatient Sample database between Q4 2015-2020. SJS patients were randomly sampled into two equal experimental and validation groups. The weight for each comorbidity was determined from a multivariable logistic regression to develop into a single SJS Index.

Results

There were 4519 SJS (mortality rate 5.05%), 873 SJS-TEN (mortality rate 13.06%), and 759 TEN (mortality rate 17.00%) patients identified. The SJS Index had good discrimination power (c-statistic=0.704, 95% CI=0.656-0.753) and was well-calibrated (Brier score=0.049). SJS Index had similar performance in multivariable regression model with all comorbidities (DeLong p-value=0.621) and validation group (DeLong p-value=0.634). The index had significantly better discriminative power than Elixhauser Comorbidity Index (ECI) (DeLong p-value=0.001). Applying the SJS Index to SJS-TEN patients showed comparable discriminative powers (DeLong test p-value=0.284). In TEN patients, SJS Index remained good calibration (Brier score=0.062) but discriminative power decreased (DeLong p-value=0.005). After adjusting for age, race, and ethnicity, SJS Index had improved performance in all groups.

Conclusions

The SJS Index can effectively discriminate and predict in-hospital mortality in SJS and was externally validated in NIS. SJS/TEN often has emergent presentation and immediate intervention is required, this risk score can give an initial assessment of the mortality based on medical records alone and thus offer a quick insight for clinicians for management. In addition, this study demonstrated the possibility of the SJS Index being used as one composite metric to develop a more comprehensive risk-calculator score.
Availability and accessibility to latrine and handwashing facilities during working hours among “boda-boda” drivers in Mwanza city
Authors: Basinda Namanya , Chilipweli Peter , Kisaka Emmanuel B. , Shoo Maxwell P. , Tupa Theckla , Vingson Marystella Z , Laizer Julieth , Konje Eveline , Kapesa Anthony , Morona Dominica
Published: May 2023

Background

Water access and sanitation are two of the most fundamental critical urban services upon which people in cities depend. Lack of these services may pose a major threat of disease especially in low- and middle-income countries. Mwanza City in Tanzania faces serious challenges regarding to sanitation services to the public and occupational on mobile bases such as Boda-boda. Boda-boda drivers are mobile and often come up into contact with people which might lead to the spread of diseases through the fecal-oral route. Thus, the aim of this study was to determine the level of accessibility and the barriers to sanitation and hygiene among the boda-boda drivers in Mwanza city.

Methods

This was a community based cross sectional study carried out in Nyamagana District that involved a randomly selected 196 participants. Data were collected using a pretested questionnaire. Data was be analyzed for frequency distribution, proportion and percentages for quantitative variables, mean ± SD.

Results

Almost a quarter(27.05%) had difficulties towards accessing latrines when they needed to use one. This was almost in parallel with 27.04% of the participants claiming latrines are not convenient in the community. Almost thirty percent (32.14%) were not satisfied with the availability of clean latrines, 67.35% claimed there are community laws or rules in place that make it more likely them to use a latrine every time they need to defecate or urinate. 84.69% showed great awareness towards realizing the importance of using latrines instead of the opposite.

Conclusion

Our results indicate that some of the Boda-boda drivers claims that latrines are not accessible and convenient but also habit has been a limiting factor which makes them to practice open defecation. Thus, there is inevitable need for the authority to build more clean latrines and run them as a business oriented low-cost facility i.e., pay per use. Together with making strict laws that enforces the use of latrine among the boda-boda drivers should be a priority.
A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion inAFF3as a significant cause of intellectual disability
Authors: Jadhav Bharati , Garg Paras , van Vugt Joke J. F. A. , Ibanez Kristina , Gagliardi Delia , Lee William , Shadrina Mariya , Mokveld Tom , Dolzhenko Egor , Martin-Trujillo Alejandro , Gies Scott L. , Rocca Clarissa , Barbosa Mafalda , Jain Miten , Lahiri Nayana , Lachlan Katherine , Houlden Henry , Paten Benedict ,   Genomics England Research Consortium,   Project MinE ALS Sequencing Consortium, Veldink Jan , Tucci Arianna , Sharp Andrew J.
Published: May 2023

GC-rich tandem repeat expansions (TREs) are often associated with DNA methylation, gene silencing and folate-sensitive fragile sites and underlie several congenital and late-onset disorders. Through a combination of DNA methylation profiling and tandem repeat genotyping, we identified 24 methylated TREs and investigated their effects on human traits using PheWAS in 168,641 individuals from the UK Biobank, identifying 156 significant TRE:trait associations involving 17 different TREs. Of these, a GCC expansion in the promoter ofAFF3was linked with a 2.4-fold reduced probability of completing secondary education, an effect size comparable to several recurrent pathogenic microdeletions. In a cohort of 6,371 probands with neurodevelopmental problems of suspected genetic etiology, we observed a significant enrichment ofAFF3expansions compared to controls. With a population prevalence that is at least 5-fold higher than the TRE that causes fragile X syndrome,AFF3expansions represent a significant cause of neurodevelopmental delay.