Miracle-dz/UniFAR-FTUs huggingface dataset:
Community health volunteers could help improve access to and use of essential health services by communities in LMICs: an umbrella review

Abstract A number of primary studies and systematic reviews focused on the contribution of community health workers (CHWs) in the delivery of essential health services. In many countries, a cadre of informal health workers also provide services on a volunteer basis [community health volunteers (CHV)], but there has been no synthesis of studies investigating their role and potential contribution across a range of health conditions; most existing studies are narrowly focused on a single condition. As this cadre grows in importance, there is a need to examine the evidence on whether and how CHVs can improve access to and use of essential health services in low- and middle-income countries (LMICs). We report an umbrella review of systematic reviews, searching PubMed, the Cochrane library, the database of abstracts of reviews of effects (DARE), EMBASE, ProQuest dissertation and theses, the Campbell library and DOPHER. We considered a review as ‘systematic’ if it had an explicit search strategy with qualitative or quantitative summaries of data. We used the Joanna Briggs Institute (JBI) critical appraisal assessment checklist to assess methodological quality. A data extraction format prepared a priori was used to extract data. Findings were synthesized narratively. Of 422 records initially found by the search strategy, we identified 39 systematic reviews eligible for inclusion. Most concluded that services provided by CHVs were not inferior to those provided by other health workers, and sometimes better. However, CHVs performed less well in more complex tasks such as diagnosis and counselling. Their performance could be strengthened by regular supportive supervision, in-service training and adequate logistical support, as well as a high level of community ownership. The use of CHVs in the delivery of selected health services for population groups with limited access, particularly in LMICs, appears promising. However, success requires careful implementation, strong policy backing and continual support by their managers.
Oral Hedgehog Pathway Inhibition as a Means for Ocular Salvage in Locally Advanced Intraorbital Basal Cell Carcinoma

BACKGROUND Basal cell cancer is the most common cutaneous malignancy. It rarely presents with locally advanced or metastatic disease. Rare presentations such as intraorbital invasion remain a difficult clinical problem with significant potential morbidity. There is no review of sonic hedgehog pathway inhibitors (HPIs) for intraorbital basal cell cancer, and evidence regarding optimal management is limited. OBJECTIVE To evaluate the evidence for the management of intraorbital basal cell cancer with HPIs. METHODS A search to identify evidence for treatment intraorbital basal cell cancers with HPIs to date was performed in PubMed database and OVID using the phrases “basal cell cancer/carcinoma/BCC,” “intraorbital,” “orbital,” “ocular,” “periocular,” “vismodegib,” “GDC-0449,” “sonidegib,” and “LDE224,” in various combinations with Boolean operators “AND” and “OR. ” RESULTS Rigorous clinical trials have previously reported the use of vismodegib and sonidegib in locally advanced and metastatic basal cell carcinoma (BCC). However, specific descriptions of treatment of intraorbital tumors are rarely presented in detail adequate for analysis. Twenty-two cases of intraorbital BCC treated with vismodegib have been described in the literature, and no cases using sonidegib were identified. These vary in quality, but highlight important questions regarding optimal treatment duration, follow-up, and adjunctive therapies. Reports describing locally advanced BCC in various facial and periocular locations, but without specific mention of intraorbital invasion, were excluded. CONCLUSION Vismodegib is an attractive eye and vision-sparing option in patients with locally advanced intraorbital basal cell cancer whose other options often include exenteration, radiation, or other radical surgery.
Impaired ankle joint mechanics during running can be resolved in people with traumatic brain injury

ABSTRACT Objectives: 1) To compare lower-limb joint mechanics during running for people with traumatic brain injury (TBI) to equivalent data obtained from a group of healthy controls (HCs); and 2) To determine if deficits identified in biomechanical variables during running for people with TBI responded to a six-month period of rehabilitation. Methods: Running biomechanics data were recorded from 12 people with TBI who were attending a large metropolitan rehabilitation hospital for mobility limitations, and a comparative sample of 10 HCs at baseline and six-month follow-up. Main Measures: Average power absorbed and generated at the hip, knee and ankle joints during stance. Results: Compared to HCs, participants with TBI at baseline ran with greater average power absorption at the hip (−0.27 W/kg vs −0.61 W/kg; p< 0.05), reduced average power absorption at the knee (−2.03 W/kg vs −1.02 W/kg; p< 0.05) and reduced average power generation at the ankle (2.86 W/kg vs 2.06 W/kg; p< 0.05). Only average power generation at the ankle improved following six-months of rehabilitation for the participants with TBI (2.06 W/kg vs 2.79 W/kg; p< 0.05). Conclusion: For the participants with TBI in the present study, recovery of high-level mobility following rehabilitation occurred alongside an improvement in ankle joint mechanics during running.
Abnormal Sleep Behaviours Across the Spectrum of Alzheimer's Disease Severity: Influence of APOE Genotypes and Lewy Bodies.

BACKGROUND The Apolipoprotein (APOE) ε4 allele is a well-known risk factor for Alzheimer's Disease (AD), and sleep disturbances are commonly associated with AD. However, few studies have investigated the relationship between APOE ε4 and abnormal sleep patterns (N+) in AD. OBJECTIVE To examine the relationship between APOE genotype, Lewy body pathology, and abnormal sleep patterns in a large group of subjects with known AD load evaluated upon autopsy. METHOD Data from 2,368 cases obtained from the National Alzheimer's Coordinating Centre database were categorized as follows: Braak Stage V/VI and CERAD frequent neuritic plaques as high load AD, Braak Stage III/IV and moderate CERAD as intermediate load AD, and Braak Stage 0/I/II and infrequent CERAD as no to low load AD. Cases discrepant between the two measures were discarded. RESULTS Disrupted sleep was more frequent in males (42.4%) compared to females (35.1%), and in carriers (42.3%) as opposed to non-carriers (36.5%) of ε4. Amongst female subjects with high AD load and Lewy body pathology, homozygous (ε4/ε4) carriers experienced disrupted sleep more often compared with heterozygous (ε4/x) or non-carriers of ε4. Such recessive, gender-specific, and Lewy body association is reminiscent of the ε4 effect on psychosis in AD. However, such association was lost after adjusting for covariates. In subjects with no to low AD pathology, female ε4 carriers had significantly more nighttime disturbances than non-carriers; this effect is independent of the presence of Lewy body pathology. CONCLUSION The influence of APOE ε4 on sleep disturbances is dependent on gender and severity of AD load.
Sexual Dimorphism of Pain Control: Analgesic Effects of Pioglitazone and Azithromycin in Chronic Spinal Cord Injury

Abstract Central neuropathic pain develops in greater than 75% of individuals suffering a spinal cord injury (SCI). Increasingly, sex is recognized as an important biological variable in the development and treatment of peripheral neuropathic pain, but much less is known about the role of sex in central neuropathic pain and its pharmacological inhibition. To test the hypothesis that efficacy of analgesic therapies differs between males and females in SCI, we used a mouse model of SCI pain to determine the analgesic efficacy of pioglitazone (PIO), U.S. Food and Drug Administration–approved drug for the treatment of diabetes, and azithromycin (AZM), a commonly prescribed macrolide antibiotic with immunomodulatory properties. Male and female mice received moderate-severe T9 contusion SCI (75-kdyn). A robust heat hyperalgesia developed similarly between male and female mice by 4 weeks post-injury and lasted throughout the duration of the study (14 weeks). Three months after SCI, mice were treated with PIO (10 mg/kg, intraperitoneal) or AZM (160 mg/kg, oral). We observed a sex-specific effect of PIO with significant antihyperalgesic effects in females, but not males. In contrast, AZM was effective in both sexes. Our data support the use of PIO and AZM as novel therapies for SCI pain and highlight the importance of considering sex as a biological variable in clinical and experimental SCI pain research.
Sweet Snacks Are Positively and Fruits and Vegetables Are Negatively Associated with Visceral or Liver Fat Content in Middle-Aged Men and Women

ABSTRACT Background Visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) are major risk factors for cardiometabolic diseases. Objective We aimed to investigate the association of dietary intake of the main food groups with VAT and HTGC in middle-aged men and women. Methods We used data from the Netherlands Epidemiology of Obesity study, a population-based study including 6671 participants aged 45–65 y at baseline. In this cross-sectional analysis, VAT and HTGC were assessed by magnetic resonance imaging and spectroscopy, respectively, as the primary outcomes. Habitual intake of main food groups (dairy, meat, fish, fruits and vegetables, sweet snacks, and fats and oils) was estimated through the use of a food-frequency questionnaire. We examined associations of intake of different food groups with VAT and HTGC by linear regression analysis stratified by sex and adjusted for age, smoking, education, ethnicity, physical activity, basal metabolic rate, energy-restricted diet, menopausal state, and total energy intake. Results In women, a 100-g/d higher intake of dairy was associated with 2.0 cm2 less VAT (95% CI: −3.4, −0.7 cm2) and a 0.95-fold lower HTGC (95% CI: 0.90-, 0.99-fold). Moreover, a 100-g/d higher intake of fruit and vegetables was associated with 1.6 cm2 less VAT (95% CI: −2.9, −0.2 cm2) in women. Fruit and vegetables were negatively associated (0.95; 95% CI: 0.91, 1.00) with HTGC, and sweet snacks were positively associated (1.29; 95% CI: 1.03, 1.63). Patterns were weaker but similar in men. Fish intake was not associated with VAT or HTGC and plant-based fat and oil intake were only associated with VAT after adjustment for total body fat. Conclusions Despite some variation in the strength of the associations between men and women, dietary intake of sweet snacks was positively associated with HTGC, and fruit and vegetable intake were negatively associated with visceral and liver fat content. Prospective studies are needed to confirm these results. The Netherlands Epidemiology of Obesity study is registered at clinicaltrials.gov with identifier NCT03410316.
Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients*

Objectives: To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice. Design: Prospective observational study. Setting: Single-center, mixed medical-surgical ICU in Europe. Patients: Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m2 and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin. Interventions: Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison. Measurements and Main Results: One-hundred twelve arterial samples (n = 112) were drawn from 20 patients (65% male; mean ± SD, 60 ± 14 yr old) with septic shock (30%), hemorrhagic shock (15%), cardiogenic shock (20%), or no circulatory shock (35%). The ICU mortality rate was 30%. Renin correlated significantly with urine output (repeated-measures correlation coefficient = –0.29; p = 0.015) and mean arterial blood pressure (repeated-measures correlation coefficient = –0.35; p < 0.001). There was no diurnal variation of renin or significant interaction of renin-angiotensin-aldosterone system drugs with renin in this population. Continuous renal replacement therapy renin removal was negligible (mass clearance ± SD 4% ± 4.3%). There was a significant difference in the rate of change of renin over time between survivors and nonsurvivors (–32 ± 26 &mgr;U/timepoint vs +92 ± 57 &mgr;U/timepoint p = 0.03; mean ± SEM), but not for lactate (–0.14 ± 0.04 mM/timepoint vs +0.15 ± 0.21 mM/timepoint; p = 0.07). Maximum renin achieved significant prognostic value for ICU mortality (receiver operator curve area under the curve 0.80; p = 0.04), whereas maximum lactate did not (receiver operator curve area under the curve, 0.70; p = 0.17). Conclusions: In an heterogeneous ICU population, renin measurement was not significantly affected by diurnal variation, continuous renal replacement therapy, or drugs. Renin served as a marker of tissue-perfusion and outperformed lactate as a predictor of ICU mortality.
Lonely But Not Alone: Neuroticism Mediates the Relationship Between Social Network Size and Loneliness in Individuals With Traumatic Brain Injury

Abstract Objectives: Although individuals with traumatic brain injury (TBI) often report higher levels of social isolation, little is known about the factors influencing their self-perception of loneliness. The aim of the current study was to investigate the relationship between loneliness, social network size, and personality variables (neuroticism and extraversion) after TBI, and in particular whether specific personality variables mediate the relationship between social network size and perception of loneliness. Methods: Here, we assessed self-reported loneliness, personality variables, and social network size of 24 individuals with moderate-to-severe TBI and 41 healthy comparison participants. We then carried out a mediation analysis to examine whether personality variables mediated the relationship between loneliness and social network size. Results: Our results indicate that individuals with TBI reported higher levels of loneliness and neuroticism, but there was no group difference in social network size or extraversion. The mediation analysis revealed that the association between social network size and loneliness was mediated by neuroticism, but not by extraversion. Conclusions: Our findings show that neuroticism is an intervening variable in the relationship between social network size and self-perception of loneliness in individuals with moderate-to-severe TBI, and presents a new possible target for clinicians and rehabilitators seeking to address reports of loneliness and social isolation in TBI. (JINS 2019, 25, 266–274)
What are the social predictors of accident and emergency attendance in disadvantaged neighbourhoods? Results from a cross-sectional household health survey in the north west of England

Objectives The aim of this study was to identify the most important determinants of accident and emergency (A&E) attendance in disadvantaged areas. Design, setting and participants A total of 3510 residents from 20 disadvantaged neighbourhoods in the North West Coast area in England completed a comprehensive public health survey. Main outcome measures Participants were asked to complete general background information, as well as information about their physical health, mental health, lifestyle, social issues, housing and environment, work and finances, and healthcare service usage. Only one resident per household could take part in the survey. Poisson regression analysis was employed to assess the predictors of A&E attendance frequency in the previous 12 months. Results 31.6% of the sample reported having attended A&E in the previous 12 months, ranging from 1 to 95 visits. Controlling for demographic and health factors, not being in employment and living in poor quality housing increased the likelihood of attending an A&E service. Service access was also found to be predictive of A&E attendance insofar as there were an additional 18 fewer A&E attendances per 100 population for each kilometre closer a person lived to a general practitioner (GP) practice, and 3 fewer attendances per 100 population for each kilometre further a person lived from an A&E department. Conclusions This is one of the first surveys to explore a comprehensive set of socio-economic factors as well as proximity to both GP and A&E services as predictors of A&E attendance in disadvantaged areas. Findings from this study suggest the need to address both socioeconomic issues, such as employment and housing quality, as well as structural issues, such as public transport and access to primary care, to reduce the current burden on A&E departments.
Report of a TREAT-NMD/World Duchenne Organisation Meeting on Dystrophin Quantification Methodology

Representatives of academia, patient organisations, industry and the United States Food and Drug Administration attended a workshop on dystrophin quantification methodology. The aims of the workshop were to provide an overview of methods used to quantify dystrophin levels in human skeletal muscle and their applicability to clinical trial samples, outline the gaps with regards to validating the methods for robust clinical applications prior to regulatory agency review, and to align future efforts towards further optimizing these methods. The workshop facilitated a constructive but also critical discussion on the potential and limitations of techniques currently used in the field of translational research (western blot and immunofluorescence analysis) and emerging techniques (mass spectrometry and capillary western immunoassay). Notably, all participants reported variation in dystrophin levels between muscle biopsies from different healthy individuals and agreed on the need for a common reference sample.
Anxiety But Not Depression Predicts Poor Outcomes in Inflammatory Bowel Disease.

BACKGROUND AND AIMS Patients with inflammatory bowel disease (IBD) have high rates of psychiatric comorbidities, but it is not clear whether those with comorbidities are at higher risk of poor outcomes. We aimed to determine whether patients with IBD who have co-existing anxiety and/or depression are more likely to have poor IBD-related outcomes compared with IBD patients without anxiety and/or depression. METHODS This was a prospective longitudinal follow-up study in Ontario, Canada, from 2008 to 2016. Patients were asked to complete questionnaires at the time of initial assessment, including the Hospital Anxiety and Depression Scale (HADS). We selected a number of clinical variables at the time of presentation and tested their ability to predict subsequent poor IBD-related outcomes, such as IBD-related hospitalization, emergency room visits, and recurrent courses of corticosteroids over the duration of follow-up. Logistic regression was used for multivariate analysis. RESULTS Four hundred fourteen IBD patients completed the baseline questionnaire. Among them, 125 had anxiety and/or depression at baseline. Factors that predicted poor IBD-related outcomes during longitudinal follow-up included increased severity of disease at initial presentation, prior IBD-related surgery, longer duration of follow-up, and elevated C-reactive protein at time of initial presentation. After adjustment for potential covariates, IBD patients with abnormal anxiety subscores had poor IBD-related outcomes compared with those without elevated anxiety subscores (odds ratio [OR] 3.36, 95% CI, 1.51-7.48). No difference in IBD-related outcomes were observed in those with abnormal depression subscores compared with those without elevated depression scores (OR 0.43, 95% CI, 0.14-1.32). CONCLUSIONS Severe disease, anxiety, and previous IBD-related surgery predict poor IBD-related outcomes in patients in the future. Closer monitoring with regular follow-up may be appropriate for patients with these risk factors.
Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV-15) compared to PCV-13 in healthy older adults

ABSTRACT Background: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) were evaluated in adults ≥ 50 years (V114-006; NCT02547649). Methods: A total of 690 subjects (230/arm) received a single dose of either PCV15 Formulation A, PCV15 Formulation B, or PCV13 and were followed for safety for 14 days postvaccination. Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and Immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured immediately prior and 30 days postvaccination. Results: Both PCV15 formulations had generally comparable safety profiles to PCV13. Baseline IgG GMCs and OPA GMTs were comparable across vaccination groups. At 30 days postvaccination, both PCV15 formulations induced serotype specific antibodies to all 15 serotypes in the vaccine. IgG GMCs and OPA GMTs in recipients of either PCV15 formulation were non-inferior (≤ 2-fold margin) to those measured in recipients of PCV13 for shared serotypes and superior (> 1.0-fold difference) for serotypes unique to PCV15. Formulation B generally induced higher immune responses than Formulation A. Conclusion: In healthy adults ≥ 50 years of age, both new formulations of PCV15 displayed acceptable safety profiles and induced serotype-specific immune responses comparable to PCV13.