The Effect of Thiazolidinediones in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type 2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. METHODS: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95 kg; 95% CI 0.03-3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85 kg/m2; 95% CI 0.13-1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56 kg/m2; 95% CI 1.77-3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74 kg/m2; 95% CI 0.07-1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD - 0.20 mmol/L; 95% CI - 0.38 to - 0.03, p = 0.02) and fasting insulin levels (MD - 11.47 mmol/L; 95% CI - 20.20, - 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD - 0.62; 95% CI - 1.25-0.00, p = 0.05). CONCLUSION: Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. PROSPERO REGISTRATION NO: CRD42020178783.

Epigenetics of conotruncal congenital heart disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Conotruncal congenital heart defects (CTD) are a subset of congenital heart diseases (CHD) that involve structural anomalies of the right, left, or both cardiac outflow tracts. CHD is caused by multifactorial inheritance and changes in the genes or chromosomes. Recently, CHD was found to be due to epigenetic alterations, which are a combination of genetic and other environmental factors. Epigenetics is the study of how a gene's function changes as a result of environmental and behavioral influences. These causative factors can indirectly cause CHD by altering the DNA through epigenetic modifications. This is a protocol for a systematic review and meta-analysis that aims to explore whether the strength of association between various epigenetic changes and CTD types varies by race. Furthermore, to determine and compare the changes in gene expression of each mutation. METHODS: Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. A comprehensive pre-search has been developed in PubMed and PubMed's Medical Subject Headings (MeSH). The final search will be performed in June 2023 in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CIANHL, and PsycInfo, without restrictions on publication years. The Covidence systematic review software will be used for blinded screening and selection. Conflicts will be resolved by a third, independent reviewer. The risk of bias in selected studies will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The data to be extracted will cover basic information on the included studies, study sample size, number of patients with various types of epigenetic changes, number of patients with various CTD types, measures of association and their 95% confidence interval between each epigenetic change and each CTD. The protocol has been registered with the International Prospero Register of Systematic Review (PROSPERO) [CRD42023377597]. DISCUSSION: To the best of our knowledge, this protocol outlines the first systematic review and meta-analysis of the epigenetics of CTD. There is a growing body of evidence on epigenetics and its indirect involvement in disease by altering the DNA through epigenetic modifications in the genes associated with the causative factors for CHD. We will conduct a comprehensive and systematic search for literature in the above-mentioned seven core biomedical databases. It is very important to identify population-specific risk factors for CHD, which will have significant creative, custom-made, and effective prevention programs for the future generation.

School bullying prevention and intervention strategies in the United Arab Emirates: a scoping review.

INTRODUCTION: Schools in the United Arab Emirates (UAE) witnessed an increase of 7% in bullying prevalence since 2005. This review aimed to map antibullying interventions in the UAE. METHODS: A systematic search was performed in five electronic databases (EMBASE, PubMed, PsycINFO, Scopus and Eric) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review. Studies addressing antibullying interventions and grey literature in the UAE from 2010 to 2021 were included. Interventions were mapped using distribution across key sectors, public health practice levels, and organisation types. RESULTS: Of the 2122 identified papers, only 2 were included. Both articles were published in 2019 and used qualitative methods. From the search of governmental and non-governmental websites, 22 multilevel interventions were included and presented on the three levels of public health practice across the different sectors and target stakeholders. Eight interventions were at the federal level, and six were by private stakeholders. The government funded 59% of all interventions. Four interventions addressed cyberbullying, and three used multisectoral collaboration. CONCLUSIONS: Although the UAE is building capacity for bullying prevention, we found limited knowledge of antibullying prevention efforts. Further studies are needed to assess current interventions, strategies and policies.

Risk of suicidal behavior in patients with major depression and bipolar disorder - A systematic review and meta-analysis of registry-based studies.

Suicide is a health priority and one of the most common causes of death in mood disorders. One of the limitations of this type of research is that studies often establish rates of suicide behaviors in mood disorders by using diverse comparison groups or simply monitoring cohort of patients over a time period. In this registry-based systematic review, national registers were identified through searches in six academic databases, and information about the occurrence of suicide behaviors in mood disorders was systematically extracted. Odds ratios were subsequently calculated comparing rates of death by suicide in mood disorders in comparison with age and period matched rates of death by suicide in the general population obtained from country-wide national registers. The aim was to provide the most recent summary of epidemiological and clinical factors associated to suicide in mood disorders whilst calculating the likelihood of death by suicide in mood disorders in comparison with non-affected individuals according to national databases. The study follows the Preferred Reporting Guidelines for Systematic Reviews and Meta-analyses and was prespecify registered on Prospero (CRD42020186857). Results suggest that patients with mood disorders are at substantially increased risk of attempting and dying by suicide. Several epidemiological, clinical and social factors are reported to be associated with clinical populations at risk of suicide. Meta-analyses of completed deaths by suicide suggest that the likelihood for dying by suicide in mood disorders is 8.62 times higher in major depression and 8.66 times higher in bipolar disorder with higher number of untoward events in women compared to men in both conditions. The likelihood of dying by suicide in major depressive disorders is higher in the first year following discharge. Clinical guidelines might consider longer periods of monitoring following discharge from hospital. Overall, due to the higher risk of suicide in mood disorders, efforts should be made to increase detection and prevention whilst focusing on reducing risk in the most severe forms of illness with appropriate treatment to promote response and remission at the earliest convenience.

Genotoxicity of Occupational Pesticide Exposures among Agricultural Workers in Arab Countries: A Systematic Review and Meta-Analysis.

Exposure to pesticides in Arab countries is a significant public health concern due to extensive agricultural activity and pesticide use. This systematic review aimed to evaluate the genotoxic effects of agricultural pesticide exposure in the region, identify research gaps, and assess methodological limitations. Following the PRISMA guidelines, a comprehensive search yielded five relevant studies conducted in Egypt, Syria, and Jordan. Various genotoxicity assays were employed, revealing a higher level of DNA damage in exposed compared to non-exposed individuals. Farmers exposed to pesticides exhibited a significantly higher occurrence of chromosomal translocation (t(14;18)), micronuclei, and chromosomal aberrations. However, only two studies assessed cytotoxicity indirectly. The studies predominantly focused on male participants, with variations in sample size and pesticide types. The lack of detailed exposure data necessitates cautious interpretation. This review underscores the need for further research on the genotoxicity of occupational pesticide exposure in the Middle East. Future studies should adopt robust study designs, collect biological and environmental samples, conduct repeated sampling, analyze seasonal variations, and encompass diverse study sites associated with specific crop groups.

Multimodal diagnostics in multiple sclerosis: predicting disability and conversion from relapsing-remitting to secondary progressive disease course - protocol for systematic review and meta-analysis.

BACKGROUND: The number of patients diagnosed with multiple sclerosis (MS) has increased significantly over the last decade. The challenge is to identify the transition from relapsing-remitting to secondary progressive MS. Since available methods to examine patients with MS are limited, both the diagnostics and prognostication of disease progression would benefit from the multimodal approach. The latter combines the evidence obtained from disparate radiologic modalities, neurophysiological evaluation, cognitive assessment and molecular diagnostics. In this systematic review we will analyse the advantages of multimodal studies in predicting the risk of conversion to secondary progressive MS. METHODS AND ANALYSIS: We will use peer-reviewed publications available in Web of Science, Medline/PubMed, Scopus, Embase and CINAHL databases. In vivo studies reporting the predictive value of diagnostic methods will be considered. Selected publications will be processed through Covidence software for automatic deduplication and blind screening. Two reviewers will use a predefined template to extract the data from eligible studies. We will analyse the performance metrics (1) for the classification models reflecting the risk of secondary progression: sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, positive and negative predictive values; (2) for the regression models forecasting disability scores: the ratio of mean absolute error to the range of values. Then, we will create ranking charts representing performance of the algorithms for calculating disability level and MS progression. Finally, we will compare the predictive power of radiological and radiomical correlates of clinical disability and cognitive impairment in patients with MS. ETHICS AND DISSEMINATION: The study does not require ethical approval because we will analyse publicly available literature. The project results will be published in a peer-review journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42022354179.

Towards a better understanding between non-Muslim primary care clinicians and Muslim patients: A literature review intended to reduce health care inequities in Muslim patients.

Although Muslims are a growing population within many non-Muslim countries, there are insufficient Muslim clinicians to care for them. Studies have shown that non-Muslim clinicians have limited knowledge and understanding of Islamic practices affecting health, which may lead to disparities in the quality of healthcare delivery and outcomes when caring for Muslim patients. Muslims come from many different cultures and ethnicities and have variations in their beliefs and practices. This literature review provides some insights which may strengthen therapeutic bonds between non-Muslim clinicians and their Muslim patients resulting in improved holistic, patient-centered care in the areas of cancer screening, mental health, nutrition, and pharmacotherapy. Additionally, this review informs clinicians about the Islamic perspective on childbirth, end of life issues, travel for Islamic pilgrimage, and fasting during the month of Ramadan. Literature was sourced by a comprehensive search in PubMed, Scopus, and CINAHL along with hand screening of citations. Title and abstract screening followed by full-text screening excluded studies including less than 30% Muslim participants, protocols, or reporting results deemed irrelevant to primary care. 115 papers were selected for inclusion in the literature review. These were grouped into the themes of general spirituality, which were discussed in the Introduction, and Islam and health, Social etiquette, Cancer screening, Diet, Medications and their alternatives, Ramadan, Hajj, Mental health, Organ donation and transplants, and End of life. Summarizing the findings of the review, we conclude that health inequities affecting Muslim patients can be addressed at least in part by improved cultural competency in non-Muslim clinicians, as well as further research into this area.

Are encapsulated pesticides less harmful to human health than their conventional alternatives? Protocol for a systematic review of in vitro and in vivo animal model studies.

BACKGROUND: The gradual increase in the global population has led to the rising demand for agricultural products worldwide. This required the introduction of environment- and public health-friendly advanced technologies for plant protection to guard yields from pest destruction in a sustainable way. Encapsulation technology is a promising procedure to increase the effectiveness of pesticide active ingredients while reducing human exposure and environmental impact. Despite the presumed favorable properties of encapsulated pesticide formulations on human health, it is necessary to systematically assess whether they are less harmful to human health than conventional pesticide products. OBJECTIVES: We aim to systematically review the literature to answer the question of whether micro- or nano-encapsulated pesticide formulations exert different degrees of toxicity than their conventional (not-encapsulated) counterparts in in vivo animal and in vitro (human, animal, and bacterial cell) non-target models. The answer is important to estimate the possible differences in the toxicological hazards of the two different types of pesticide formulations. Because our extracted data will come from different models, we also aim to perform subgroup analyses to investigate how toxicity varies across different models. A pooled toxicity effect estimate will also be performed by meta-analysis when appropriate. METHODS: The systematic review will follow the guidelines developed by the National Toxicology Program's Office of Health Assessment and Translation (NTP/OHAT). The protocol adheres to the Preferred Reporting Items for Systematic Reviews and meta-analyses Protocol (PRISMA-P) statement. PubMed (NLM), Scopus (Elsevier), Web of Science Core Collection (Clarivate), Embase (Elsevier), and Agricola (EBSCOhost) electronic databases will be comprehensively searched in September 2022 to identify eligible studies using multiple search terms of "pesticide", "encapsulation" and "toxicity" along with their synonyms and other words that are semantically related. The reference lists of all eligible articles and retrieved reviews will be manually screened to identify additional relevant papers. ELIGIBILITY CRITERIA: We will include peer-reviewed experimental (non-target in vivo animal model and in vitro human, animal, and bacterial cell cultures) studies published as full-text articles in English language that simultaneously investigate the effect of any micro- or nano-encapsulated pesticide formulation, applied in all ranges of concentrations, duration, and routes of exposure, and its corresponding active ingredient(s) or its conventional non-encapsulated product formulation(s) used in the same ranges of concentrations, duration, and routes of exposure on the same pathophysiological outcome. We will exclude studies that examine pesticidal activity on target organisms, cultures of cells isolated from target organisms exposed in vivo or in vitro, and those using biological materials isolated from target organisms/cells. STUDY APPRAISAL AND SYNTHESIS: Studies identified by the search will be screened and managed according to the review inclusion and exclusion criteria in the Covidence systematic review tool by two reviewers, who will also blindly extract the data and assess the risk of bias of included studies. The OHAT risk of bias tool will be applied to evaluate the quality and risk of bias in the included studies. Study findings will be synthesized narratively by important features of the study populations, design, exposure, and endpoints. If findings make it possible, a meta-analysis will be performed on identified toxicity outcomes. To rate the certainty in the body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Polycystic ovarian syndrome among women diagnosed with infertility in the Gulf Cooperation Council countries: A protocol for systematic review and meta-analysis of prevalence studies.

BACKGROUND: Polycystic ovarian syndrome, a common endocrine disorder, is an important cause of infertility among women of reproductive age. Within the Gulf Cooperation Council countries, polycystic ovarian syndrome is found to affect women increasingly. No study has been carried out to critically summarize the evidence on the prevalence of polycystic ovarian syndrome among women suffering from infertility in these countries. OBJECTIVE: This protocol aims to conduct a systematic review and meta-analysis of the studies reporting the prevalence of polycystic ovarian syndrome among women seeking infertility treatment in the six Gulf Cooperation Council countries (Bahrain, Kuwait, Oman, Saudi Arabia, Qatar, and United Arab Emirates). DESIGN/METHODS AND ANALYSIS: The systematic review and meta-analysis will follow the following method. DATA SOURCE: Five databases, including PubMed, Embase, CINAHL, Web of Science, and SCOPUS, will be searched for observational studies using a combination of relevant keywords and Medical Subject Headings from inception of databases. DATA EXTRACTION: Two reviewers will screen titles and abstracts, followed by a full-text search based on the eligibility criteria. The main outcome is to measure the proportion of women who have polycystic ovarian syndrome among infertility-diagnosed patients. In addition, the risk of bias in the included studies will be assessed using the national institute of health quality assessment tool for observational studies. DATA SYNTHESIS: The random-effects method of the analysis with the inverse variance will be used to calculate the pooled prevalence of polycystic ovarian syndrome-attributed infertility. Variation in prevalence estimates will be calculated using subgroup analysis based on study and patients' characteristics and publication bias will be assessed via funnel plot inspection and Eggar's test. DISCUSSION: A critical assessment of evidence on the prevalence of polycystic ovarian syndrome in women attending fertility clinics is helpful in risk quantification, enabling better planning for managing infertility in women with polycystic ovarian syndrome. REGISTRATION: This protocol has been registered with PROSPERO, protocol registration number (CRD42022355087).

Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials.

Major depressive disorders are prevalent conditions with limited treatment response and remission. Pharmacogenomics tests including CYP2D6 and CYP2C19 genomic variants provide the most reliable actionable approach to guide choice and dosing of antidepressants in major depression to improve outcomes. We carried out a meta-analysis and meta-regression analyses of randomised controlled trials evaluating pharmacogenomic tests with CYP2D6 and CYP2C19 polymorphisms in major depression. A systematic review was conducted according to PRISMA and Cochrane guidelines to search several electronic databases. Logarithmically transformed odds ratios (OR) and confidence intervals (CI) for improvement, response and remission were calculated. A random-effects meta-analysis and meta-regression analyses were subsequently carried out. Twelve randomised controlled trials were included. Pharmacogenomic tests in the treatment of depression were more effective than treatment as usual for improvement (OR:1.63, CI: 1.19-2.24), response (OR: 1.46; CI: 1.16-1.85) and remission (OR: 1.85; CI: 1.23-2.76) with no evidence of publication bias. Remission was less favourable in recent studies. The results are promising but cautious use of pharmacogenomics in major depression is advisable. PROSPERO registration ID: CRD42021261143.

The Benefits of Utilizing Continuous Glucose Monitoring of Diabetes Mellitus in Primary Care: A Systematic Review.

BACKGROUND: Continuous glucose monitoring (CGM) and intermittently scanned CGM (is-CGM) have shown to effectively manage diabetes in the specialty setting, but their efficacy in the primary care setting remains unknown. Does CGM/is-CGM improve glycemic control, decrease rates of hypoglycemia, and improve staff/physician satisfaction in primary care? If so, what subgroups of patients with diabetes are most likely to benefit? METHODS: A comprehensive search in seven databases was performed in June 2021 for primary studies examining any continuous glucose monitoring system in primary care. We excluded studies with fewer than 20 participants, specialty care only, or hospitalized participants. The National Heart, Lung and Blood Institute and Grading of Recommendations Assessment, Development and Evaluation were used for the quality assessment. The weighted mean difference (WMD) of HbA1c between CGM/is-CGM and usual care with 95% confidence interval was calculated. A narrative synthesis was conducted for change of time in, above, or below range (TIR, TAR, and TBR) hypoglycemic events and staff/patient satisfaction. RESULTS: From ten studies and 4006 participants reviewed, CGM was more effective at reducing HbA1c compared with usual care (WMD -0.43%). There is low certainty of evidence that CGM/is-CGM improves TIR, TAR, or TBR over usual care. The CGM can reduce hypoglycemic events and staff/patient satisfaction is high. Patients with intensive insulin therapy may benefit more from CGM/is-CGM. CONCLUSIONS: Compared with usual care, CGM/is-CGM can reduce HbA1c, but most studies had notable biases, were short duration, unmasked, and were sponsored by industry. Further research needs to confirm the long-term benefits of CGM/is-CGM in primary care.

Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. AIM: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. DATA SOURCE: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. DATA SYNTHESIS: Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI  - 0.49 to  - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI  - 1.34 to  - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD:  - 0.47; 95% CI  - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD:  - 0.37 µg/dL; 95% CI  - 0.05 to  - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD:  - 1.67; 95% CI  - 2.27 to  - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed. CONCLUSION: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects. PROSPERO REGISTRATION NO: CRD42020178783.

Interprofessional education in health professions education programmes in the Arab world: a scoping review protocol.

INTRODUCTION: Interprofessional education is a relatively new addition to health professional education curricula in the Arab world. To understand current practice in this area, a scoping review will enable reporting of essential elements for the implementation of interprofessional education. The objective of this scoping review is to report on the implementation components, including presage, process and product, of interprofessional education in prelicensure health professions education programmes in the Arab world. METHODS AND ANALYSIS: A comprehensive and systematic search for literature will be conducted using eight electronic databases from their inception to September 2022. A presearch was devised in PubMed, Scopus and CINAHL using a combination of terms related to population, context and concept. The Covidence Systematic Review tool will be used for blind screening, selection and conflict resolution. Data will be presented in tabular format and as a narrative synthesis and will include elements that support the implementation of interprofessional education. This review will be presented according to the Joanna Briggs Institute methodology.Studies conducted with students and/or faculty in prelicensure health professions education programmes will be included. The concept to be explored is interprofessional education. The context is the region commonly known as the Arab world, which includes 18 countries, sharing many common social and cultural traditions and where Arabic is the first language.Excluded will be studies conducted on collaborative practice of health professionals and postlicensure interprofessional education. ETHICS AND DISSEMINATION: No ethical approval was required. Findings will be disseminated in conference presentations and peer-reviewed articles.

Impact of metformin on the clinical and metabolic parameters of women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

Context: Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition. Aim: To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS. Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022. Data synthesis: Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: -5.33, -0.93), body mass index (BMI) by 0.82 kg/m² (95% CI: -1.22, -0.41), fasting blood glucose [standardised mean difference (SMD): -0.23; 95% CI: -0.40, -0.06], low-density lipoprotein cholesterol (LDL-C) (SMD: -0.41; 95% CI: -0.85, 0.03), total testosterone (SMD: -0.33; 95% CI: -0.49, -0.17), androstenedione (SMD: -0.45; 95% CI: -0.70, -0.20), 17-hydroxyprogesterone (17-OHP) (SMD: -0.58; 95% CI: -1.16, 0.00) and increase the likelihood of clinical pregnancy rate [odds ratio (OR): 3.00; 95% CI: 1.95, 4.59] compared with placebo. Conclusion: In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.

The role of microbiota in immunotherapy outcomes in colorectal cancer patients: A protocol for a systematic review.

In the human gut, there are many microbes, including bacteria, viruses and parasites. The imbalance in the numbers of each type of these microbes can translate into gastrointestinal disorders. Lately, different microbiota patterns have been associated with the levels of efficacy of immunotherapy in multiple cancer conditions. Studies have shown that patients with a more diverse gut microbiome respond better to immunotherapy than those with a homogeneous microbiome. This systematic review aims to identify and assess the available evidence on the efficacy of immunotherapy in treating colorectal cancer (CRC) patients and the effect of their microbiota on their treatment outcomes. The researchers will study the literature regarding CRC and immunotherapy outcomes to survey the different approaches employed to assess the treatment outcomes. A systematic search will be performed in five biomedical databases (PubMed, Scopus, Web of Science, Embase, and the Cochrane Library) in June-July, 2022. Also, open-access registers of clinical trials will be trawled. The search will be conducted without geographical or publication date restrictions; however, only papers published in the English language will be sought. Details regarding patients' diets, lifestyles, and characteristics will be assessed. We will define the primary outcome to compare CRC patients' immunotherapy responses with their gut microbiota composition. The systematic review methodology does not require ethics approval due to the nature of the study design. The systematic review results will be published in an open-access peer-reviewed journal. PROSPERO ID: CRD42021277691.

Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models: A Systematic Review.

Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS.

Risk factors associated with quadbike crashes: a systematic review.

BACKGROUND: Quadbikes or all-terrain vehicles are known for their propensity for crashes resulting in injury, disability, and death. The control of these needless losses resulting from quadbike crashes has become an essential contributor to sustainable development goals. Understanding the risk factors for such injuries is essential for developing preventive policies and strategies. The aim of this review was to identify the risk factors associated with quadbike crashes at multiple levels through a systematic review of a wide range of study designs. METHODS: The study incorporated a mixed-method systematic review approach and followed the PRISMA 2020 guidelines for reporting systematic reviews, including a peer reviewed  protocol. This systematic review included observational studies investigating the risk factors associated with quadbike crashes, injuries, or deaths. Seven electronic databases were searched from inception to October 2021. Studies were screened and extracted by three researchers. Quality appraisal was conducted using the Mixed Methods Appraisal Tool (MMAT). Due to extensive heterogeneity, meta-analysis was not conducted. All the risk factors have been presented in a narrative synthesis for discussion following the guidelines for Synthesis without Meta-analysis (SWiM). RESULTS: Thirty-nine studies combining an aggregate of 65,170 participants were included in this systematic review. The results indicate that modifiable risk factors, such as the increasing age of driving initiation, reducing substance use, and the use of organized riding parks, could reduce quadbike injuries. Riding practices such as avoiding passengers, avoiding nighttime riding, and using helmets could significantly reduce crashes and injuries among riders. Vehicle modifications such as increasing the wheelbase and limiting engine displacement could also help reduce crash incidence. Traditional interventional methods, such as legislation and training, had a weak influence on reducing quadbike injuries. CONCLUSION: Multiple risk factors are associated with quadbike injuries, with most of them modifiable. Strengthening policies and awareness to minimize risk factors would help in reducing accidents associated with quadbikes. PROSPERO registration number CRD42020170245.

A Systematic Review of Insulin Management Recommendations to Improve Glycemic Control and Reduce Hypoglycemic Events During Ramadan Fasting in Patients With Insulin-Requiring Type 2 Diabetes.

Background: Muslims with insulin-requiring type 2 diabetes are at high risk of hypo- and hyperglycemia while fasting during the month of Ramadan. Although a few reviews on diabetic management during Ramadan have been published, surveys reveal knowledge gaps remain among physicians. Aim: This systematic review qualitatively analyzes what insulin dosing recommendations are likely to reduce hypoglycemic events and improve glycemic control during the Ramadan fasting for this high-risk group. Methods: A comprehensive search in six databases and gray sources was performed from August 10, 2001, to August 10, 2021, for studies assessing which types of insulin and/or what dosing recommendations reduce hypoglycemic events and improve glycemic control during Ramadan. We excluded studies focusing mainly on oral antihyperglycemic medications, type 1 diabetes, persons with insulin pumps, and studies older than 20 years. Hypoglycemic event rates, pre-, and post-iftar blood glucose levels, overall average blood glucose, and hemoglobin A1c were analyzed, and a narrative synthesis was performed. Results: Out of 1,101 collected articles, 14 eligible studies including 2,969 participants with an average age of 54.8 years, we found that insulin dose reduction may prevent hypoglycemia without causing subsequent hyperglycemia, and rapid-acting insulin analogs may improve post-iftar and overall blood glucose without incurring hypoglycemia. Conclusions: Though initial findings are promising, more research is needed to confirm the benefits of insulin dose reduction, rapid-acting insulin analogs, and ultra-long-acting insulins. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021268943.

A systematic review and meta-analysis to assess the relationship between sleep duration/quality, mental toughness and resilience amongst healthy individuals.

The majority of sleep research has focused on deleterious health outcomes, with little attention to positive sequels. A systematic review of the literature regarding sleep duration and/or sleep quality in relation to mental toughness and resilience amongst non-clinical, healthy populations was completed. Eight databases and selected sources for grey literature were searched from their inception to April 2021. A total of 1925 unique records (1898 from the database search and 27 from grey sources) were identified and screened against the pre-set inclusion and exclusion criteria. Of these, 68 studies were eligible and 63 were included in the meta-analysis. Pooled results indicated a weak, positive correlation between sleep duration and resilience (r = 0.11, p < 0.001), and sleep quality (r = 0.27, p < 0.001). The pooled correlation was slightly attenuated for prospective studies pertaining to sleep quality and resilience (r = 0.18, p < 0.001). We found evidence of high publication bias for studies that explored the relationship between sleep quality and resilience. Sleep and resilience are positively correlated but additional research is needed to verify the direct relationship through carefully designed, prospective studies that capture both subjective and objective sleep estimates. For a more comprehensive understanding, complementary reviews that explore the sleep-resilience association are needed for clinical populations, and those who have suffered extreme hardship.