Epidemiology of gonorrhea in the World Health Organization European Region, 1949-2021: Systematic review, meta-analyses, and meta-regressions

Background: Epidemiology of Neisseria gonorrhoeae (NG) infection remains inadequately understood. Aim: Characterizing NG epidemiology in Europe. Methods: Cochrane and PRISMA guidelines were followed to systematically review, report, synthesize, and analyze NG prevalence data up to September 30, 2021. Random-effects meta-analyses estimated pooled prevalence. Meta-regression analyses investigated associations and sources of heterogeneity. Results: 844 publications were included yielding 1,573 overall and 2,199 stratified NG prevalence measures. Pooled prevalence of current urogenital infection was 1.0% (95% CI: 0.7-1.2%) among general populations, 3.2% (95% CI: 1.8-4.8) among female sex workers, 4.9% (95% CI: 4.2-5.6%) among sexually transmitted infection clinic attendees, and 12.1% (95% CI: 8.8-15.8%) among symptomatic men. Among men who have sex with men (MSM), pooled prevalence was 0.9% (95% CI: 0.5-1.4%), 5.6% (95% CI: 3.6-8.1%), and 3.8% (95% CI: 2.5-5.4%) for current urogenital, anorectal, and oropharyngeal infection, respectively. Current urogenital, anorectal, and oropharyngeal infection was 1.45-fold (95% CI: 1.19-1.77), 2.75-fold (95% CI: 1.89-4.02), and 2.64-fold (95% CI: 1.77-3.93) higher, respectively, among men compared to women. Current urogenital infection declined by 0.97-fold (95% CI: 0.96-0.98) yearly over the last few decades, but current anorectal and oropharyngeal infection increased by 1.02-fold (95% CI: 1.01-1.04) and 1.02-fold (95% CI: 1.00-1.04) yearly, respectively. Conclusions: NG epidemiology in Europe has two distinct and contrasting epidemiologies for vaginal sex transmission in heterosexual sex networks versus anal and oral sex transmission in MSM sexual networks. Increased transmission may facilitate drug-resistant strain emergence. Europe is far from achieving the World Health Organization target of 90% incidence reduction by 2030

Vitamin D3 metabolite ratio as an indicator of vitamin D status and its association with diabetes complications

Background: Vitamin D deficiency is diagnosed by total serum 25-hydroxyvitamin D (25(OH)D) concentration and is associated with poor health and increased mortality; however, some populations have low 25(OH) D concentrations without manifestations of vitamin D deficiency. The Vitamin D Metabolite Ratio (VMR) has been suggested as a superior indicator of vitamin D status. Therefore, VMR was determined in a population with type 2 diabetes at high risk for vitamin D deficiency and correlated with diabetic complications.Research design and methods: Four hundred sisty patients with type 2 diabetes (T2D) were recruited, all were vitamin D3 supplement naive. Plasma concentration of 25-hydroxyvitamin D3 (25(OH)D3) and its metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and its epimer, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), were measured by LC-MS/MS analysis. VMR-1 was calculated as a ratio of 24,25(OH)2D3:25(OH)D3; VMR-2 as a ratio of 1,25(OH)2D3:25(OH)D3; VMR-3 was calculated as a ratio of 3-epi-25(OH)D3: 25(OH)D3. RESULTS: An association means that there were significant differences between the ratios found for those with versus those without the various diabetic complications studied. VMR-1 was associated with diabetic retinopathy (p = 0.001) and peripheral artery disease (p = 0.012); VMR-2 associated with hypertension (p Conclusions: In this cross sectional study, whilst not causal, VMR-2 was shown to be the superior predictor of diabetic and cardiovascular complications though not demonstrative of causality in this cross-sectional study population over VMR-1, VMR-3 and the individual vitamin D concentration measurements; VMR-2 associated with both microvascular and cardiovascular indices and therefore may have utility in predicting the development of diabetic complications.</p

Association of vitamin D2 and D3 with type 2 diabetes complications

Aims Vitamin D measurement is a composite of vitamin D2 (25(OH)D2) and D3 (25(OH)D3) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D2 supplements. This study was undertaken to determine if vitamin D2 and D3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D2 and vitamin D3 levels in subjects with T2DM. Methods Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D2 and D3 were measured by LC-MS/MS analysis. Results All subjects were taking vitamin D2 and none were taking D3 supplements. Vitamin D2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p  Conclusions In this Qatari cohort, vitamin D2 was associated with hypertension and dyslipidemia, whilst vitamin D3 levels were associated with diabetic retinopathy. Vitamin D2 levels were higher, whilst vitamin D3 were lower in diabetics and females, likely due to ingestion of vitamin D2 supplements.Other Information Published in: BMC Endocrine Disorders License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1186/s12902-020-00549-w</p

A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control (vol 58, pg 1855, 2015)

Aims/hypothesis: Metabolomics has opened new avenues for studying metabolic alterations in type 2 diabetes. While many urine and blood metabolites have been associated individually with diabetes, a complete systems view analysis of metabolic dysregulations across multiple biofluids and over varying timescales of glycaemic control is still lacking. Methods: Here we report a broad metabolomics study in a clinical setting, covering 2,178 metabolite measures in saliva, blood plasma and urine from 188 individuals with diabetes and 181 controls of Arab and Asian descent. Using multivariate linear regression we identified metabolites associated with diabetes and markers of acute, short-term and long-term glycaemic control. Results: Ninety-four metabolite associations with diabetes were identified at a Bonferroni level of significance (p &lt; 2.3 &times; 10&minus;5), 16 of which have never been reported. Sixty-five of these diabetes-associated metabolites were associated with at least one marker of glycaemic control in the diabetes group. Using Gaussian graphical modelling, we constructed a metabolic network that links diabetes-associated metabolites from three biofluids across three different timescales of glycaemic control. Conclusions/interpretation: Our study reveals a complex network of biochemical dysregulation involving metabolites from different pathways of diabetes pathology, and provides a reference framework for future diabetes studies with metabolic endpoints

Point of Care Exome Sequencing Reveals Allelic and Phenotypic Heterogeneity Underlying Mendelian disease in Qatar

The effectiveness of next generation sequencing at solving genetic disease has motivated the rapid adoption of this technology into clinical practice around the world. In this study, we use whole exome sequencing (WES) to assess 48 patients with Mendelian disease from 30 serial families as part of the Qatar Mendelian Disease pilot program -a coordinated multi-center effort to build capacity and clinical expertise in genetic medicine in Qatar. By enrolling whole families (parents plus available siblings), we demonstrate significantly improved discriminatory power for candidate variant identification over trios for both de novo and recessive inheritance patterns. For the same index cases, we further demonstrate that even in the absence of families, variant prioritization is improved up to 8-fold when a modest set of population-matched controls is used vs large public databases, stressing the poor representation of Middle Eastern alleles in presently available databases. Our in-house pipeline identified candidate disease variants in 27 of 30 families (90%), 23 of which (85%) harbor novel pathogenic variants in known disease genes, pointing to significant allelic heterogeneity and founder mutations underlying Mendelian disease in the Middle East. For 6 of these families, the clinical presentation was only partially explained by the candidate gene, suggesting phenotypic expansion of known syndromes. Our pilot study demonstrates the utility of WES for Middle Eastern populations, the dramatic improvement in variant prioritization conferred by enrolling population-matched controls and/or enrolling additional unaffected siblings at the point-of-care, and 25 novel disease-causing alleles, relevant to newborn and premarital screening panels in regional populations