Prevalence, severity, and risk factors of disability among adults living with HIV accessing routine outpatient HIV care in London, United Kingdom (UK): A cross-sectional self-report study.

BACKGROUND: The study objectives were to measure disability prevalence and severity, and examine disability risk factors, among adults living with HIV in London, United Kingdom (UK). METHODS: Self-reported questionnaires were administered: World Health Organization Disability Assessment Schedule 2.0 (WHODAS), HIV Disability Questionnaire (HDQ), Equality Act disability definition (EADD), and demographic questionnaire. We calculated proportion (95% Confidence Interval; CI) of "severe" and "moderate" disability measured using EADD and WHODAS scores ≥2 respectively. We measured disability severity with HDQ domain severity scores. We used demographic questionnaire responses to assess risk factors of "severe" and "moderate" disability using logistic regression analysis, and HDQ severity domain scores using linear regression analysis. RESULTS: Of 201 participants, 176 (87.6%) identified as men, median age 47 years, and 194 (96.5%) virologically suppressed. Severe disability prevalence was 39.5% (n = 79/201), 95% CI [32.5%, 46.4%]. Moderate disability prevalence was 70.5% (n = 141/200), 95% CI [64.2%, 76.8%]. Uncertainty was the most severe HDQ disability domain. Late HIV diagnosis was a risk factor for severe disability [Odds Ratio (OR) 2.71; CI 1.25, 5.87]. Social determinants of health, economic inactivity [OR 2.79; CI 1.08, 7.21] and receiving benefits [OR 2.87; CI 1.05, 7.83], were risk factors for "severe" disability. Economic inactivity [OR 3.14; CI 1.00, 9.98] was a risk factor for "moderate" disability. Economic inactivity, receiving benefits, and having no fixed abode were risk factors (P≤0.05) for higher HDQ severity scores in physical, mental and emotional, difficulty with day-to-day activities, and challenges to social participation domains. Personal factors, identifying as a woman and being aged <50 years, were risk factors (P≤0.05) for higher HDQ severity scores in mental and emotional, uncertainty, and challenges with social participation domains. CONCLUSIONS: People living with well-controlled HIV in London UK experienced multi-dimensional and episodic disability. Results help to better understand the prevalence, severity, and risk factors of disability experienced by adults living with HIV, identify areas to target interventions, and optimise health and functioning.

Current controversies: Null hypothesis significance testing.

Traditional null hypothesis significance testing (NHST) incorporating the critical level of significance of 0.05 has become the cornerstone of decision-making in health care, and nowhere less so than in obstetric and gynecological research. However, such practice is controversial. In particular, it was never intended for clinical significance to be inferred from statistical significance. The inference of clinical importance based on statistical significance (p < 0.05), and lack of clinical significance otherwise (p ≥ 0.05) represents misunderstanding of the original purpose of NHST. Furthermore, the limitations of NHST-sensitivity to sample size, plus type I and II errors-are frequently ignored. Therefore, decision-making based on NHST has the potential for recurrent false claims about the effectiveness of interventions or importance of exposure to risk factors, or dismissal of important ones. This commentary presents the history behind NHST along with the limitations that modern-day NHST presents, and suggests that a statistics reform regarding NHST be considered.

Influence of previous delivery mode on perineal trauma risk.

OBJECTIVE: To evaluate the impact of a previous pregnancy and delivery on perineal trauma rates in the subsequent vaginal birth. METHODS: Retrospective cohort study. The perineal outcomes of secundiparous women with history of previous (first) delivery in one of three categories: failed operative vaginal delivery (FOVD) and second-stage emergency cesarean section (EmCS); elective cesarean section (ElCS), and vaginal delivery (VD) with intact perineum, were compared with a control primiparous group. RESULTS: The percentage obstetric anal sphincter injuries (OASIS)at first vaginal delivery was 17.3% (n = 9) after previous FOVD+EmCS, 12.9% (n = 18) after previous ElCS, and 0.6% (n = 9) after previous VD maintaining an intact perineum, compared with 6% (n = 1193) in the control primiparous group of women. Multivariate regression analysis demonstrated that previous FOVD+EmCS and ElCS were associated with a statistically significant increased risk of OASIS of 180% and 110% when compared with control (odds ratio [OR] 2.80; 95% confidence interval [CI] 1.35-5.78 and OR 2.10; 95% CI 1.27-3.48, respectively). Previous VD with intact perineum was associated with a statistically significantly reduced risk of OASIS (OR 0.09; 95% CI 0.04-0.17). CONCLUSIONS: Previous FOVD+EmCS and ElCS were associated with increased risk of OASIS in subsequent vaginal delivery compared with control, whereas previous VD with intact perineum was associated with decreased risk.

Defining the Mean Angle of Diaphyseal Long Bone Nonunions-Does Shear Prevail?

OBJECTIVES: To define the mean angle of a series of diaphyseal nonunions based on radiographic analysis. DESIGN: A retrospective cohort study. SETTING: Two level-1 trauma centers. PATIENTS: One hundred twenty patients presenting with nonunion. INTERVENTION: A mean nonunion angle was calculated from a series of AP and lateral X-rays using a standardized technique. The nonunion angle was then estimated in a single plane by considering the greater of the 2 measured angles. Additional data collected included patient age, sex, nonunion site, initial fracture angle, and original fracture pattern. MAIN OUTCOME MEASUREMENT: Single plane nonunion angle. RESULTS: The mean angles of all nonunion in coronal plane was 42 degrees (SD 17 degrees) and 42 degrees in sagittal plane (SD 18 degrees) and 48 degrees (SD 15 degrees) in single plane. The single plane nonunion angle in fractures which were originally multiplanar was steeper to those occurring in originally single plane fractures (P 0.002) although both were close to 45 degrees. There was no significant difference in the nonunion angles on subgroup analysis of cohort location, sex, or anatomic location. CONCLUSIONS: This study demonstrates the mean angle of diaphyseal nonunions from long bones of the lower limb approaches 45 degrees. This is noted in all types of fractures and is irrespective of anatomic location or sex. This confirms the hypothesis that shear is likely to play a role in the development of a nonunion. This study provides further evidence that nonunions occur primarily because of mechanical instability. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Erythrocyte Encapsulated Thymidine Phosphorylase for the Treatment of Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy: Study Protocol for a Multi-Centre, Multiple Dose, Open Label Trial.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder which primarily affects the gastrointestinal and nervous systems. This disease is caused by mutations in the nuclear TYMP gene, which encodes for thymidine phosphorylase, an enzyme required for the normal metabolism of deoxynucleosides, thymidine, and deoxyuridine. The subsequent elevated systemic concentrations of deoxynucleosides lead to increased intracellular concentrations of their corresponding triphosphates, and ultimately mitochondrial failure due to progressive accumulation of mitochondrial DNA (mtDNA) defects and mtDNA depletion. Currently, there are no treatments for MNGIE where effectiveness has been evidenced in clinical trials. This Phase 2, multi-centre, multiple dose, open label trial without a control will investigate the application of erythrocyte-encapsulated thymidine phosphorylase (EE-TP) as an enzyme replacement therapy for MNGIE. Three EE-TP dose levels are planned with patients receiving the dose level that achieves metabolic correction. The study duration is 31 months, comprising 28 days of screening, 90 days of run-in, 24 months of treatment and 90 days of post-dose follow-up. The primary objectives are to determine the safety, tolerability, pharmacodynamics, and efficacy of multiple doses of EE-TP. The secondary objectives are to assess EE-TP immunogenicity after multiple dose administrations and changes in clinical assessments, and the pharmacodynamics effect of EE-TP on clinical assessments.

Results from an online survey of adults with cystic fibrosis: Accessing and using life expectancy information.

Cystic fibrosis (CF) is the one of the most common inherited diseases. It affects around 10,000 people in the UK, and the median survival age is 47. Recent developments making use of longitudinal patient registry data are producing more detailed and relevant information about predicted life expectancy in CF based on current age and clinical measurements. The objective of this study was toconduct an online survey of adults with CF living in the UK using a web-based questionnaire to investigate: (i) if and how they access information on life expectancy; (ii) what they use it for; (iii) if they want more personalised information on life expectancy or the time until other milestones. The survey was advertised through the Cystic Fibrosis Trust using social media. There were 85 respondents, covering men (39%) and women (61%) aged 16-65. 75% had received information on life expectancy either from their CF care team (34%) or other sources (71%), the most common being the Cystic Fibrosis Trust website and research literature. Most people who received information found it to be beneficial and reported using it in a variety of ways, including to plan strategies for maintaining as best health as possible and to psychologically manage current health status. 82% of respondents were interested in more personalised information about their life expectancy, and participants also noted interest in other outcomes, including time to needing transplant or reaching a low level of lung function. Themes arising in text responses included the importance of good communication of information, the difficulty of relating general information to one's own circumstances, and a desire for increased information on factors that impact on survival in CF. As an outcome from this work, research is underway to establish how information on life expectancy can be presented to people with CF in an accessible way.

Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder.

INTRODUCTION: FGF-2 is important for stem cell proliferation, neocortical development and adult neuronal survival and growth. Reduced frontal cortical FGF-2 expression is described in major depression and is attenuated by antidepressants. We determined the distribution of hippocampal FGF-2 and its receptor (FGFR1) mRNA in post-mortem brains of people who suffered from major depression, bipolar disorder and schizophrenia and those of controls. METHODS: FGF-2 and FGFR1 mRNA were measured within hippocampal CA1, CA4 regions and the dentate gyrus (DG), using in situ hybridization. Within hippocampal regions, cellular staining was compared between diagnostic groups, using repeated measures analysis of variance. RESULTS: The density of FGF-2 mRNA+ cells in CA4 was reduced in depression compared to controls. The percentage of FGFR1 mRNA+ cells was higher in depression (CA1 and CA4) and schizophrenia (CA4) than in controls. FGFR1 mRNA expression was higher in depression than in the other groups in CA1, CA4 and DG. Overall FGF-2 mRNA expression was higher in DG than in CA1 and CA4. CONCLUSIONS: We found raised measures of FGFR1 mRNA+ in major depression and, less so, in schizophrenia, along with reduced FGF-2 mRNA density in depression. Perturbations of FGF regulation could be relevant to the pathogenesis of both disorders as FGF-2 and FGFR1 are implicated in normal hippocampal synaptology, stem cell recruitment, and connectivity, and are modulated by corticosteroids.

Management of acute renal colic in the UK: a questionnaire survey.

BACKGROUND: There is great variation in the Accident and Emergency workload and location of Urology services in UK hospitals. This study investigated the relationship of the initial management of acute renal colic with the department workload plus local facilities including location of X-ray and urology services in UK Accident and Emergency (A&E) departments. METHODS: A&E departments in each of the 11 UK Deanery regions were stratified based on departmental workload, namely <30,000 (small); 30,000 to 50,000 (medium); 50,000 to 80,000 (large) and >80,000 (very large) patients per year. One third of departments were selected in each group leading to a sample size of 106. A questionnaire was administered. Associations between categorical variables were investigated using the chi-squared test and when not valid, Fisher's Exact test was employed. Differences between groups in ordinal variables were investigated using the Mann-Whitney test. RESULTS: All questionnaires were returned. Twenty-nine units (27.4%) did not perform any radiological investigation on renal colic patients. The number of radiological investigations that were available to departments was associated with workload (P = 0.003); with 57.1% of the small departments performing none and at least 82.8% of units in the other categories performing at least one. Of those departments with X-ray facilities in or adjacent to the department, 63% performed an intravenous urography (IVU) compared to 25% of those departments without (P = 0.026). Of those departments with on-site urology services, 86% performed at least one radiological investigation compared to 52% of units without such services (P = 0.001). Department workload was associated with the first choice analgesia (NSAIDs or parenteral opiates) (P = 0.011). Of the small departments, 64.3% used NSAIDs, 21.4% used parenteral opiates and 14.3% used neither. In comparison, NSAIDS were used by at least 87%, and opiates by at most 12.5% of units in each of the other three categories of department workload. CONCLUSIONS: Over a quarter of UK A&E departments did not perform any radiological investigations and some departments do not even offer renal colic patients any analgesia. Patient management was associated with departmental workload, location of X-ray and Urology services. National guidelines are needed to ensure optimum care for all patients.