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Reports on the risk and prognosis of breast cancer in relation to the sex of a child have been conflicting. Since medical sciences play an important role in informing sociocultural understandings of health and illness, evidence-based studies have the potential to foster or counter stigma and shape social attitudes toward a newborn’s sex.To pool all available evidence to provide the highest level of evidence on the association between the sex of the first child and breast cancer risk or prognosis.Systematic review and meta-analyses.A comprehensive search using three databases was conducted from inception until May 2020. Titles and abstracts of all papers identified were independently screened by two authors. Data extraction and quality assessment were also performed independently by two researchers. The breast cancer risk was quantified using the odds ratio, and the prognosis (i.e., mortality) was measured using the risk ratio.In the meta-analysis, 11 studies with more than 1 million participants were included. The pooled estimate from the five studies on risk and the six studies on prognosis were odds ratio 0.99 (95% confidence interval, 0.95-1.03) and risk ratio 1.00 (95% confidence interval, 0.80-1.26), respectively.When we pooled all available evidence, the sex of the firstborn child was neither associated with risk nor prognosis in breast cancer. Clinically, our findings are reassuring and important, especially in light of previous studies that recommended differential treatment and counseling based on the sex of the first child. Socially, our findings challenge conventional social stereotypes that regard male children as biologically superior to female children.

This cross-sectional study examines the Doi-Alshoumer PCOS clinical phenotype classification in relation to measured clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS). Two cohorts of women (Kuwait and Rotterdam) diagnosed with PCOS (FAI > 4.5%) were examined. These phenotypes were created using neuroendocrine dysfunction (IRMA LH/FSH ratio > 1 or LH > 6 IU/L) and menstrual cycle status (oligo/amenorrhea) to create three phenotypes: (A) neuroendocrine dysfunction and oligo/amenorrhea, (B) without neuroendocrine dysfunction but with oligo/amenorrhea, and (C) without neuroendocrine dysfunction and with regular cycles. These phenotypes were compared in terms of hormonal, biochemical, and anthropometric measures. The three suggested phenotypes (A, B, and C) were shown to be sufficiently distinct in terms of hormonal, biochemical, and anthropometric measures. Patients who were classified as phenotype A had neuroendocrine dysfunction, excess LH (and LH/FSH ratio), irregular cycles, excess A4, infertility, excess T, highest FAI and E2, and excess 17αOHPG when compared to the other phenotypes. Patients classified as phenotype B had irregular cycles, no neuroendocrine dysfunction, obesity, acanthosis nigricans, and insulin resistance. Lastly, patients classified as phenotype C had regular cycles, acne, hirsutism, excess P4, and the highest P4 to E2 molar ratio. The differences across phenotypes suggested distinct phenotypic expression of this syndrome, and the biochemical and clinical correlates of each phenotype are likely to be useful in the management of women with PCOS. These phenotypic criteria are distinct from criteria used for diagnosis.

Background. The global increase in type 2 diabetes (T2D) poses a significant public health challenge worldwide. Due to the chronic and complex nature of the disease, management does not depend on pharmacotherapy alone; rather, a comprehensive medical and self-management plan is required. Diabetes Self-Management Education programs should address diabetes-specific behaviors and be grounded in patients’ perceptions of their disease and its consequences. Aim. The study aims to understand perceptions of diabetes self-management (DSM) among persons of different nationalities with T2D living in Qatar. Method. A phenomenological qualitative study was implemented using four focus group interviews using Triandis Interpersonal Behavior Model to understand factors influencing DSM perceptions and behaviors. Therefore, deductive content analysis was used, also inductive content analysis used to find new emerging themes. Twenty-nine participants with T2D of 12 different nationalities were recruited. Results. Content analyses revealed that participants were mainly motivated to manage their diabetes by fear of future health complications—and the resulting impact on their families—triggered by witnessing these complications on other family members and friends. Factors that influenced DSM included cultural factors such as food content and holidays’ customs, weather conditions, psychological distress, and social factors such as lack of family support. Furthermore, access to healthy food, number of working hours and time, and cost of DSM supplies were found to be among the barriers to DSM. Conclusion. Understanding and considering patients’ perspectives is a core component of culturally competent and evidence-based DSM programs, and it should be considered in any DSM program.

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Aims With the rising number of outcomes being reported following gestational diabetes (GDM), the outcomes in existing studies vary widely making it challenging to compare and contrast the effectiveness of different interventions for GDM. The purpose of this study was to develop a core outcome and measurement set (COS) for GDM treatment trials. Materials & Methods A Delphi study with structured consultation with stakeholders and discussion within a specialist Gestational Metabolic Group (GEM) were combined with a comprehensive systematic search across different databases (PubMed, Cochrane Library, and Embase). Several Delphi rounds over 2 years were conducted culminating in this report. Results The process resulted in a targeted set of outcomes constituting a “GEM treatment set” aligned with expert opinion. The final COS also included a measurement set for the 11 important clinical outcomes from three major domains: maternal metabolic, fetal, and pregnancy related. Conclusions Based on the results of this study, it is recommended that future clinical trials on GDM report outcomes uniformly keeping to the recommended COS outcomes.

The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1-7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes- and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels

This study outlines the development of a new method (split component synthesis; SCS) for meta-analysis of diagnostic accuracy studies and assesses its performance against the commonly used bivariate random effects model.The SCS method summarizes the study-specific diagnostic odds ratio (on the ln(DOR) scale), which mainly reflects test discrimination rather than threshold effects, and then splits the summary ln(DOR) into its component parts, logit sensitivity (Se) and logit specificity (Sp). Performance of SCS estimator was assessed through simulation and compared against the bivariate random effects model estimator in terms of bias, mean squared error (MSE), and coverage probability across varying degrees of between-studies heterogeneity.The SCS estimator for the DOR, Se, and Sp was less biased and had smaller MSE than the bivariate model estimator. Despite the wider width of the 95% confidence intervals under the bivariate model, the latter had a poorer coverage probability than that under the SCS method.The SCS estimator outperforms the bivariate model estimator and thus represents an improvement in the approach to diagnostic meta-analyses. The SCS method is available to researchers through the diagma module in Stata and the SCSmeta function in R.

To compare the efficacy of remnant ablation following a single low dose (specific activity ofNineteen studies have reported the results of low doseThe average failure of a single low dose was 46 ± 28% (SD). Meta-analysis revealed a statistically significant advantage for a single high over a single low dose and a pooled reduction in relative risk of failure of the high dose of about 27% (P 0.01). From this we estimate that for every seven patients treated one more would be ablated given a high rather than a low dose (assuming a low dose failure risk of 50%). Also, a significantly greater proportion of patients are ablated after a single high or low dose, if they underwent near-total as opposed to sub-total thyroidectomy (summary relative risk (RR) 1.4; P 0.05).High dose

The right ventricular apex (RVA) is the traditional lead site for chronic pacing but in some patients may cause impaired left ventricular (LV) systolic function over time. Comparisons with right ventricular nonapical (RVNA) pacing sites have generated inconsistent results and recent meta-analyses have demonstrated unclear benefit due to heterogeneity across studies.A systematic search for randomized controlled trials that compared LV ejection fraction (LVEF) outcomes between RVNA and RVA pacing was performed up to October 2014. Twenty-four studies (n = 1,628 patients) met the inclusion criteria. To avoid between study heterogeneity two homogenous groups were created; group 1 where studies reported a difference (in favor of RVNA pacing) and group 2 where studies reported no difference between pacing sites. For group 1, weighted mean difference between RVNA and RVA pacing in terms of LVEF at follow-up was 5.40% (95% confidence interval [CI]: 3.94-6.87), related in part to group one's RVA arm demonstrating a significant reduction (mean loss -3.31%; 95% CI: -6.19 to -0.43) in LVEF between study baseline and end of follow-up. Neither of these finding were seen in group 2. Weighted regression modeling demonstrated that inclusion of poor baseline LVEF (40%) in combination with greater than 12 months follow-up was three times more common in group 1 compared to group 2 (weighted relative risk 2.82; 95% CI: 1.03-7.72; P = 0.043).In patients requiring chronic right ventricular pacing where there is inclusion of impaired baseline LVEF (40%), RVA pacing is associated with deterioration in LV function relative to RVNA pacing.

Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS classifications and in relation to whole gland histopathology following radical prostatectomy. Multivariate logistic regression modeling and clinical risk (incorporating standard clinicopathological variables) were performed for all ejaculate-based markers.While Hepsin alone was not of predictive value, the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate composite score based on multivariate logistic regression, was shown to be a better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676) and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659) risk stratification criteria as classified using prostate biopsies. It was also possible to analyse a subgroup of patients for miRNA expression with miR-200c (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while a combination of serum PSA, miR-200c, and miR-125b further improved prediction for prostate cancer status when compared to PSA alone determined by biopsy (AUC 0.869 vs. 0.672; P0.05), and risk (D'Amico/PRIAS) as well as by radical prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by biopsy, at a sensitivity of 90%, the specificity of the test increased from 11% for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b.These results show that use of a combination of different types of genetic markers in ejaculate together with serum PSA are at least as sensitive as those reported in DRE urine. Furthermore, a combination of serum PSA and selected miRNAs improved prediction of prostate cancer status. This approach may be helpful in triaging patients for MRI and biopsy, when confirmed by larger studies.

Rosiglitazone has previously been widely used to treat patients with type 2 diabetes mellitus, but its safety in terms of cardiovascular morbidity and mortality had been called into question. Recently, there have been doubts raised about the meta-analytic evidence with the regulatory authorities relaxing its restrictions. We hypothesized that the original analyses may have produced exaggerated results because of the small baseline risks involved. To demonstrate this, we replicated the meta-analysis of four randomized trials of greater than 12-month follow-up that made use of a randomized control group not receiving rosiglitazone and reported outcome data for all occurrences of the complementary outcomes (no myocardial infarction, no death from cardiovascular causes, and no heart failure). Data were combined by means of a fixed-effects model. In the rosiglitazone group, as compared with the control group, the relative risk for no myocardial infarction was 0.997 (95% confidence interval [CI], 0.994 to 1.000), and the relative risk for no death from cardiovascular causes was 1.001 (95%CI, 0.999 to 1.003). Finally, no heart failure had a relative risk of 0.995 (95%CI, 0.993 to 0.998). Rosiglitazone does not seem to have any significant increase in the risk of myocardial infarction or of death from cardiovascular causes associated with its use. Regulatory authorities should revisit this issue of the appropriate measure for reporting of adverse events with low baseline risks as this has implications well beyond rosiglitazone.

A unique challenge in meta-analysis of observational studies is bias adjustment. Two different approaches have been proposed for doing this - using summary scores versus component scores. The prevailing view on this matter is that summary quality scores are inaccurate because information from its components can cancel each other out.A head-to-head comparison of the component score adjustment with our method using summary scores is undertaken, using data reported by the authors of the component method.It is demonstrated that the consideration of components or of aggregate scores does indeed lead to the same conclusions. Yet, the latter does not require imputation of the direction and magnitude of changes to effect sizes.The summary quality score used for bias adjustment within the context of an appropriate model may be most expedient. Implications for the bias adjustment of meta-analyses of observational studies are discussed.

The level of evidence-based practice (EBP) and awareness has not been previously assessed among primary care physicians in Kuwait. The objectives of this study were to quantify the level of EBP and awareness in Kuwait and identify the factors related to EBP.We used a cross sectional study that enrolled 332 primary care physicians in 57 primary care centres randomly chosen in Kuwait. A self-administered questionnaire was used to collect the data with a response rate of about 93%.Although half of the physicians self reported that they use EBP most of the time, further analysis revealed that only about 24% of this group had a reasonable understanding of EBP. Most of the clinical practice in the Kuwaiti primary care system seems to be based on the clinician's own judgment or what they learned in the medical school and traditional text books, rather than evidence-based sources. None of the physicians had an Internet connection at their work place and a vast majority of them had no access to international journals nor were confident about critical appraisal of published evidence.Overall level of awareness of evidence-based medicine (EBM) among primary care physicians in Kuwait was considerably low. Training in the areas of EBM as well as making sure the Kuwaiti primary care centres have access to evidence-based sources are critically important if primary care in Kuwait were to become evidence based.

The purpose of the present study was to evaluate the efficacy of corticosteroids in the treatment of Graves' ophthalmopathy in comparison to other treatment modalities.15 studies were identified but only 14 were included in the final analysis, 5 cohort and 9 randomized. A total of 813 patients were included in this quantitative review.The relative risk with oral corticosteroid treatment (OCS) alone vs. other treatment could not be pooled, as the studies were heterogeneous and the RR was dependent on risk of failure in the control group. In the two studies that reported head-on comparison between OCS and radiotherapy, no clinically significant difference was found. However, the combination of OCS and radiotherapy was markedly more effective than either modality alone (pooled RRR 70%). The number of patients who should be treated with the combination of CS and radiotherapy to prevent one more failure was between 3 to 8. Evidence from the studies suggest that intravenous corticosteroid's IVCSs used alone have similar or greater efficacy than the combination.Corticosteroids seem to be an effective treatment for Graves' ophthalmopathy compared to other treatments currently available. Oral corticosteroids appear to have increased effect when given with radiotherapy. IVCSs, with or without radiotherapy, seem to have the best documented efficacy. Side effects can also be overcome by the use of IVCS pulse therapy (without OCS), which needs to be pursued in further, separate research as an alternative to oral therapy, since it could be both more effective and safer.