Childhood, adolescent, and adulthood adiposity are associated with risk of PCOS: a Mendelian randomization study with meta-analysis.

STUDY QUESTION: What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Excess body fat, even during childhood/adolescence, and metabolic parameters, suggestive of hyperinsulinaemia/insulin resistance, significantly impact the risk of PCOS in a linear fashion. WHAT IS KNOWN ALREADY: Observational and Mendelian randomization (MR) data have demonstrated an association between adulthood overweight/obesity and development of PCOS. However, the contribution of body composition in childhood/adolescence to incident PCOS is unclear, as is the influence of childhood overweight/obesity. STUDY DESIGN, SIZE, DURATION: We conducted a systematic review and meta-analysis and integrated our results with a previously published systematic review. Two blinded investigators screened abstracts published between November 2010 and May 2021. Furthermore, we incorporated summary statistics from genome-wide association study (GWAS) data in subjects of European ancestry. Adult overweight was defined as BMI ≥ 25 kg/m2 and obesity as BMI ≥ 30 kg/m2; in Asian subjects, overweight was defined as BMI ≥ 23 kg/m2 and obesity as BMI ≥ 25 kg/m2. PARTICIPANTS/MATERIALS, SETTING, METHODS: We utilized meta-analysis and MR together to allow synthesis of genetic and observational data. For the systematic review, the search revealed 71 studies, of which 63 were included in meta-analysis by calculating odds ratios (ORs) using the random-effects model. Furthermore, we conducted a two-sample MR study of GWAS data to determine the impact of childhood and adult body size (defined categorically by BMI and childhood body size proportions), abnormal body composition and metabolic parameters (higher fasting serum insulin or lower sex hormone-binding globulin (SHBG) concentration) on the odds of incident PCOS via the inverse-variance weighted method. MAIN RESULTS AND THE ROLE OF CHANCE: Significant associations were shown between body composition and PCOS incidence. From the systematic review/meta-analysis, women with overweight (OR 3.80, 2.87-5.03), obesity (OR 4.99, 3.74-6.67), and central obesity (OR 2.93, 2.08-4.12) had increased odds of PCOS. For adolescents with overweight and/or obesity, the PCOS odds were greater than for adults. From MR, for every standard deviation increase in BMI (4.8 kg/m2), the odds of PCOS increased by 2.76 (2.27-3.35). Childhood body size had an independent effect on PCOS odds after adjusting for adult body size (OR: 2.56, 1.57-4.20). Genetically determined body fat percentage (OR 3.05, 2.24-4.15), whole body fat mass (OR 2.53, 2.04-3.14), fasting serum insulin (OR 6.98, 2.02-24.13), and SHBG concentration (OR 0.74, 0.64-0.87) were all significantly associated with PCOS in a linear relation. LIMITATIONS, REASONS FOR CAUTION: The meta-analysis included studies which were cross-sectional and retrospective, limiting our ability to determine causality. MR was limited by interrogating subjects only of European ancestry and including cases classified by either self-diagnosis or diagnostic criteria. WIDER IMPLICATIONS OF THE FINDINGS: Our study demonstrates for the first time a critical role of the impact of excess childhood/adolescent adiposity on the pathophysiology of adult PCOS. Our results, driven by genetically determined childhood/adolescent body composition, higher BMI, hyperinsulinaemia, and lower SHBG, clearly favour obesity driving the metabolic, but not reproductive, PCOS phenotype. Overall, effective weight maintenance, even from the early years, is likely to reduce the risk of this reproductive endocrine disorder. STUDY FUNDING/COMPETING INTEREST(S): S.S.Z. was funded by a National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship. U.A. is chair of the NIHR Steering Committee Trial-CASSANDRA-DN. No other authors declare any sources of funding or relevant conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relations that could be construed as a potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The value of administering intravenous antibiotics during haemodialysis in the treatment of diabetic foot infections.

OBJECTIVE: People with diabetes who are on haemodialysis (HD) are at a high risk of diabetic foot infections (DFI) and related complications. We explored the value of treating DFI with intravenous (IV) antibiotics during HD. METHOD: This was an observational study of consecutively treated patients with DFIs with IV antibiotics during HD. Data collected included baseline characteristics, IV antibiotics used, details of multidisciplinary interventions and DFI treatment outcome. RESULTS: A cohort of 11 patients, mean (±standard deviation) age 62.4±12.7 years, had 15 episodes of treatment with IV antibiotics during HD. Of the patients, six (54.5%) were male and nine (81.8%) had type 2 diabetes. The estimated mean glomerular filtration rate (eGFR) was 11.4±3.9ml/minute. All patients had infected foot ulceration, soft tissue infection, six (54.5%) patients had osteomyelitis, and two (18.2%) had wet gangrene. The commonest IV antibiotic used was vancomycin (10/15 episodes, 66.7%). Other IV antibiotics used were daptomycin and meropenem. In three episodes, oral ciprofloxacin was used with IV antibiotics. The mean duration of antibiotic treatment was 9.2±4.9 weeks. Of the episodes, 11 (73.3%) were treated successfully with IV antibiotics alone and two (13.3%) episodes required minor surgical debridement/amputation. Some 10 (90.9%) members of the cohort had peripheral arterial disease and of those, five (50%) underwent angioplasty during IV antibiotic treatment. CONCLUSION: HD provides a good opportunity for treatment with IV antibiotics in DFI. This mode of administration of IV antibiotics, along with multidisciplinary intervention, is associated with ulcer healing and resolution of infection in over three-quarters of patients with DFI. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

Diagnostic delay in axial spondyloarthritis: a systematic review and meta-analysis.

BACKGROUND: Delay to diagnosis in axial SpA (axSpA) is longer than in many other rheumatic diseases. Prolonged delay is associate with poorer outcomes, including functional impairment and quality of life. Our aims were to describe global variation in delay to diagnosis, factors associated with delay, and delay compared with PsA. METHODS: We searched MEDLINE, PubMed, Embase and Web of Science using a predefined protocol. Diagnostic delay was defined as years between the age at symptom onset and at diagnosis. We pooled the mean delay using random effects inverse variance meta-analysis. We examined variations in pooled estimates using prespecified subgroup analyses and sources of heterogeneity using meta-regression. RESULTS: A total of 64 studies reported the mean diagnostic delay in axSpA patients. The pooled mean delay was 6.7 years (95% CI 6.2, 7.2) with high levels of heterogeneity. Delay to diagnosis did not improve over time when stratifying results by year of publication. Studies from high-income countries (defined by the World Bank) reported longer delays than those from middle-income countries. Factors consistently reported to be associated with longer delays were lower education levels, younger age at symptom onset and absence of extra-articular manifestations (EAMs). The pooled estimate for diagnostic delay from 8 PsA studies was significantly shorter, at 2.6 years (95% CI 1.6, 3.6). CONCLUSION: For axSpA patients, delay to diagnosis remains unacceptably prolonged in many parts of the world. Patient factors (e.g. education) and disease presentation (onset age and EAMs) should inform campaigns to improve delay.

Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis.

OBJECTIVE: To describe the prevalence of extra-articular manifestations-enthesitis, dactylitis, nail disease, uveitis and IBD-in PsA, and their impact on longitudinal disease outcomes. METHODS: We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies using imaging to define extra-articular manifestations (EAMs) were excluded. Where possible, we performed meta-analyses of prevalence estimates, reported as percentages (95% CI). Heterogeneity (I2 statistic) was examined according to study characteristics. RESULTS: We identified 65 studies amounting to a total of 163 299 PsA patients. Enthesitis was assessed in 29 studies with an average prevalence of 30% (95% CI: 24%, 38%). Dactylitis was reported in 35 studies with an average prevalence of 25% (95% CI: 20%, 31%). Nail disease was present in 60% (95% CI: 52%, 68%) across 26 studies, but definitions were often unclear. Uveitis (3.2%; 95% CI: 1.9%, 5.3%) and IBD (3.3%; 95% CI: 1.5%, 7.1%) were less common. Heterogeneity was high (>95%) in all meta-analyses, but could not be explained by study characteristics. No studies examined the impact of EAMs on longitudinal disease outcomes, except that dactylitis increases radiographic progression. CONCLUSION: Enthesitis, dactylitis and nail disease are highly prevalent in PsA, but not uveitis and IBD. EAM patterns differ from axial SpA despite their shared disease mechanisms, which may help further understand differences between spondyloarthritides. More studies are needed on the impact of EAMs on disease outcomes such as response to treatment.

The prevalence and impact of depression in primary systemic vasculitis: a systematic review and meta-analysis.

OBJECTIVE: To describe the prevalence of depression among patients with primary systemic vasculitides (PSV); compare prevalence according to vasculitis type and against controls; and examine the impact of depression on PSV outcomes. METHODS: We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with PRISMA guidelines. We included all studies that reported the prevalence or impact of depression in PSV. We also included polymyalgia rheumatica (PMR) given its association with giant cell arteritis (GCA). Meta-analyses of prevalence estimates were performed using random-effects models and reported as percentages (95% confidence interval). RESULTS: We reviewed a total of 15 studies that described the prevalence of depression, categorised into small (n = 10) and large vessel vasculitis (n = 7). Pooled prevalence estimate for depression in a small vessel (predominantly ANCA-associated) vasculitis was 28% (95% CI 20-38%) with significant heterogeneity (I2 = 93%). Depression prevalence in large-vessel vasculitis (Takayasu and GCA/PMR) was 24% (95% CI 17-34%), again with significant heterogeneity (I2 = 96%). One study reported 56% prevalence of depression in medium vessel disease. The prevalence of depression in small vessel vasculitis was higher than healthy controls. In these patients, depression and depressive symptoms were associated with poorer quality of life, adherence, and work disability, but not disease activity or damage. CONCLUSION: Depression is highly prevalent among patients with primary systemic vasculitis and associated with poorer outcomes across a range of measures in studies of small vessel disease. Further studies are needed for depression in medium and large vessel vasculitides.

Driving and glaucoma in the UK: a national survey of clinicians' advice and guidance to patients.

INTRODUCTION: Driving standards policy is set by the Department for Transport and executed by the Driving and Vehicle Licensing Agency (DVLA). Professional bodies recognise the challenges that clinicians face when advising patients with glaucoma about driving. This study explored clinicians' knowledge and confidence around driving standards and their approach to advising and guiding patients. METHODS: Cross-sectional online survey of all United Kingdom and Eire Glaucoma Society (UKEGS) members. The survey remained open for five weeks (22/02/21-27/03/21). Anonymised data were exported to Microsoft Excel for analysis. RESULTS: Out of 91 respondents (minimum response rate 20.2%), 53 (58.2%) were glaucoma consultants, 2 (2.2%) general consultant ophthalmologists, 4 (4.4%) ophthalmology fellows, 5 (5.5%) ophthalmology trainees, 19 (20.9%) optometrists, and 8(8.8%) 'other' categories (one SAS doctor, six specialist doctors, one nurse specialist). 58.2% reported that the visual standards for driving were 'very familiar'; 40.5% were 'moderately familiar'; one(1.2%) was only 'somewhat familiar'; none were completely unfamiliar. A total of 38 (41.8%) respondents were highly confident in giving advice on fitness to drive; 51 (56.0%) were moderately confident; 2 (2.2%) had only limited confidence. Over 25% review patients not meeting driving standards in every glaucoma clinic, over 50% identifying abnormal visual fields as the main reason. CONCLUSION: Our study found that most clinicians are familiar with DVLA driving standards. However, busy clinical environments limit detailed discussion about this, leading to only one in four clinicians being very confident to broach the subject with patients in clinic. A range of patient education modalities were suggested, which may help simplify advice provision for glaucoma patients.

Telemedicine in Arab Countries: Innovation, Research Trends, and Way Forward.

Background: The progress and innovation in telemedicine within the Middle Eastern countries have not been heavily monitored. Therefore, the present study aims to analyze the scholarly work conducted in the Arab world, using reproducible statistical and scientometric techniques. Methods: An electronic search of Web of Science (core database) had been conducted through use of an extensive search strategy comprising of keywords specific to the Arab region, EMRO countries, telehealth, medical conditions, and disorders. A total yield of 1,630 search results were processed, indexed through July 7, 2020. CiteSpace (5.7.R1, Drexel University, Pennsylvania, USA) is a Java-based application, a user-friendly tool for conducting scientometric analyses. Results: The present analyses found a lack of innovation in the field of digital health in the Arab countries. Many gaps in research were found in Arab countries, which will be discussed subsequently. Digital health research was clustered around themes of big data and artificial intelligence; a lack of progress was seen in telemedicine and digital health. Furthermore, only a small proportion of these publications had principal or corresponding authors from Arab countries. A clear disparity in digital health research in the Arab world was evident after comparing these insights with our previous investigation on telemedicine research in the global context. Conclusion: Telemedicine research is still in its infancy in the Middle Eastern countries. Recommendations include diversification of the research landscape and interdisciplinary collaborations in this area.