Researchers have explored choroidal features in the eyes of diabetic patients without clinically visible diabetic retinopathy (DM-NoDR) employing optical coherence tomography angiography (OCTA); however, the results are controversial. We systematically searched PubMed, Embase, and Ovid databases for OCTA studies comparing choroidal parameters between DM-NoDR eyes and healthy controls or non-proliferative diabetic retinopathy (NPDR) eyes. Outcomes included choriocapillaris (CC) perfusion density (PD), flow area (FA), and flow deficits (FD). 36 studies were finally included in the quantitative meta-analysis, involving 1,908 DM-NoDR eyes, 792 NPDR eyes, and 1,391 healthy control eyes. DM-NoDR eyes had significantly lower CC PD in the foveal region (P=0.0005) and superior parafoveal region (P=0.003) than healthy control eyes, but no significant difference was found in other parafoveal subregions (P>0.05). DM-NoDR eyes were also associated with increased CC FD (P<0.00001) and decreased CC FA (P<0.0001) in whole OCTA images with a 3×3 mm2 field of view (FOV). Compared with all-stage NPDR eyes, DM-NoDR eyes had higher CC PD in the foveal region (P<0.0001), parafoveal region (P<0.00001), and the whole OCTA images with a 6×6 mm2 FOV (P<0.00001). Early choroidal microvascular changes may precede clinically visible DR and can be detected early using OCTA in DM-NoDR eyes.

UNASSIGNED: The Yi Shen Juan Bi (YSJB) pill has been used to treat rheumatoid arthritis (RA), with several studies reporting its anti-inflammatory effects and ability to prevent bone destruction. However, the lack of evidence regarding the effectiveness and toxicity of individual components of YSJB limits its widespread use.
UNASSIGNED: This protocol outlines a systematic review and/or meta-analysis to evaluate the effectiveness and safety of YSJB.
UNASSIGNED: We will search worldwide electronic databases, including MEDLINE, Cochrane Library, China National Knowledge Infrastructure, Wanfang, CiNii, J-STAGE, KoreaMed, Korean Medical Database, Korean Studies Information Service System, National Digital Science Library, Korea Institute of Science and Technology Information, and Oriental Medicine Advanced Searching Integrated System. In addition, we will conduct manual searches, and, if necessary, contact authors directly. The search will cover publications until June 2024.
UNASSIGNED: We will select randomized controlled trials (RCTs) that compare the use of YSJB for the treatment of RA against other treatments.
UNASSIGNED: Data from the selected RCTs will be extracted, including sample size, patient characteristics, intervention details, and outcome measures. We will perform a meta-analysis using Review Manager software.
UNASSIGNED: The primary outcome measures will include disease activity scores such as effective rate, swollen joint count, tender joint count, and morning stiffness. Secondary outcome measures will include blood test results and adverse events.
UNASSIGNED: The results will reveal the effectiveness and safety of YSJB for the treatment of RA.
UNASSIGNED: and Relevance: The findings will provide an evidence-based review of the use of YSJB for RA.S.

BACKGROUND: Difficult-to-treat Rheumatoid arthritis (D2T RA) is primarily characterised by failure of at least two different mechanism of action biologic/targeted synthetic disease-modifying antirheumatic drug (DMARDs) with evidence of active/progressive disease. While a variety of drugs have been used in previous studies to treat D2T RA, there has been no systematic summary of these drugs. This study conducted a systematic review of randomized controlled trials aimed at analyzing the efficacy and safety of individual therapeutic agents for the treatment of D2T RA and recommending the optimal therapeutic dose.
METHODS: The English databases were searched for studies on the treatment of D2T RA published between the date of the database\'s establishment and March, 2024. This study uses R 3.1.2 for data analysis, and the rjags package runs JAGS 3.4.0.20. The study fitted a stochastic effects Bayesian network meta-analysis for each outcome measure.
RESULTS: A total of 42 studies were included in this study. Compared with placebo, the improvement of Disease Activity Score of 28 Joints (DAS28) score is ranked from high to low as tocilizumab, baricitinib and opinercept. The improvement of American College of Rheumatology 50 response (ACR50) score in patients with drug use was ranked from good to poor as follows: olokizumab, tocilizumab, adalimumab, baricitinib, and upadacitinib, and 8 mg/4w tocilizumab demonstrated the best efficacy. Notably, rituximab is generally the safest drug. Janus kinase (JAK) inhibitors and T cell costimulation modulators are effective in D2T RA refractory to biologic DMARDs, while JAK inhibitors and interleukin-6 (IL-6) inhibitors show effectiveness in D2T RA refractory to csDMARDs.
CONCLUSIONS: Tocilizumab and rituximab have better efficacy and safety in the treatment of D2T RA, and the 8 mg/4w dose of tocilizumab may be the first choice for achieving disease remission.

X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.

Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10-0.26, P < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic.

Background: While evidence-based practice has demonstrated its capacity to enhance healthcare quality and bolster clinical outcomes, the translation of research into clinical practice encounters persistent challenges. In Ethiopia, there remains a dearth of comprehensive and nationally representative data concerning the extent of Evidence-based practice adoption among nurses. Thus, this systematic review and meta-analysis endeavors to assess the overall prevalence of Evidence-based practice implementation and delve into its determinants among Ethiopian nurses. Methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines. In order to identify pertinent studies, a search was conducted across PubMed, Scopus, Google Scholar, and EMBASE databases. A weighted inverse variance random-effects model was employed to estimate the pooled prevalence. Cochrane\'s Q-test and I2 statistics were calculated to assess heterogeneity among studies. Funnel plots and Egger\'s test were utilized to evaluate publication bias. Pooled implementation rates and meta-regression analysis were carried out using STATA 17. Results: Of the total 1,590 retrieved articles, twelve studies including 4,933 nurses were included in the final analysis. The pooled prevalence of Evidence-based practice uptake among nurses in Ethiopia is 53% (95% CI: 46%-60%). Having knowledge about Evidence-based practice (AOR = 2.29; 95% CI: 1.90, 2.69; I2 = 70.95%), holding a favorable attitude towards Evidence-based practice (AOR = 2.56; 95% CI: 1.63, 3.49; I2 = 88.39%), occupying a head nurse position (AOR = 3.15; 95% CI: 1.85, 4.46; I2 = 87.42%), possessing effective communication skills (AOR = 4.99; 95% CI: 1.47, 8.51; I2 = 99.86%), and having access to Evidence-based practice guidelines (AOR = 1.90; 95% CI: 1.55, 2.24; I2 = 57.24%) were identified as predictors of the uptake of Evidence-based practice. Conclusion: Only half of Ethiopia\'s nurses exhibit a strong embrace of Evidence-Based Practice within clinical settings, underscoring the urgent necessity for coordinated endeavors to cultivate this essential practice. Possessing knowledge, effective communication skills, access to updated guidelines, maintaining a positive attitude towards Evidence-Based Practice, and holding a position as head nurse emerged as predictors of successful implementation of Evidence-Based Practice. Hence, policymakers must prioritize capacity-building initiatives, disseminate the latest EBP guidelines widely, and strengthen mentorship roles for head nurses. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CRD42023488943.

BACKGROUND: Human Immunodeficiency Virus (HIV) continues to be the major cause of childhood deaths, particularly in the sub-Saharan African region. In Ethiopia, though several primary studies have been conducted on the incidence of HIV-related child mortality, the pooled incidence density mortality rate among HIV-positive children is unknown. Therefore, this systematic review and meta-analysis aimed to estimate the pooled incidence density mortality rate among HIV-positive children and identify its associated factors in Ethiopia.
METHODS: We browsed PubMed, HINARI, Science Direct, Google Scholar, African Journals Online, and cross-references using different search terms to identify articles. Quality appraisal was done using the Joanna Briggs Institute checklist. Meta-package was used to estimate the pooled incidence of mortality and hazard ratio (HR) of predictors. Heterogeneity was tested using the I-square statistics. Publication bias was tested using a funnel plot visual inspection and Egger\'s test. Data was presented using forest plots and tables. The random effect model was used to compute the pooled estimate.
RESULTS: The overall pooled incidence density mortality rate among HIV-positive children was 2.52 (95% CI: 1.82, 3.47) per 100 child years. Advanced HIV disease (hazard ratio (HR): 3.45, 95% CI (Confidence Interval): 2.64, 4.51), tuberculosis co-infection (HR: 3.19, 95% CI: 2.08, 4.88), stunting (3.22, 95% CI: 2.46, 4.22), underweight (HR: 2.71, 95% CI: 1.72, 4.26), wasting (HR: 4.14, 95% CI: 2.27, 7.58), didn\'t receive Isoniazid preventive therapy (HR: 3.33, 95% CI: 2.22, 4.99), anemia (HR: 3.03, 95% CI: 2.52, 3.64), fair or poor antiretroviral therapy adherence (HR: 4.14, 95% CI: 3.28, 5.28) and didn\'t receive cotrimoxazole preventive therapy (HR: 3.82, 95% CI: 2.49, 5.86) were factors associated with a higher hazard of HIV related child mortality.
CONCLUSIONS: The overall pooled incidence density mortality rate among HIV-positive children was high in Ethiopia as compared to the national strategy target. Therefore, counseling on antiretroviral therapy adherence should be strengthened. Regular monitoring of hemoglobin levels and assessment of nutritional status should be done for all children living with HIV. Moreover, healthcare professionals should follow the national HIV treatment guidelines and provide cotrimoxazole preventive therapy and Isoniazid preventive therapy up on the guidelines for children living with HIV.
BACKGROUND: Registered in PROSPERO with ID: CRD42023486902.

BACKGROUND: Psilocybin, a naturally occurring psychedelic compound found in certain species of mushrooms, is known for its effects on anxiety and depression. It has recently gained increasing interest for its potential therapeutic effects, particularly in patients with advanced cancer. This systematic review and meta-analysis aim to evaluate the effects of psilocybin on adult patients with advanced cancer.
OBJECTIVE: To investigate the therapeutic effect of psilocybin in patients with advanced cancer.
METHODS: A comprehensive search of electronic databases was conducted in PubMed, Cochrane Central Register of Controlled Trials, and Google Scholar for articles published up to February 2023. The reference lists of the included studies were also searched to retrieve possible additional studies.
RESULTS: A total of 7 studies met the inclusion criteria for the systematic review, comprising 132 participants. The results revealed significant improvements in quality of life, pain control, and anxiety relief following psilocybin-assisted therapy, specifically results on anxiety relief. Pooled effect sizes indicated statistically significant reductions in symptoms of anxiety at both 4 to 4.5 months [35.15 (95%CI: 32.28-38.01)] and 6 to 6.5 months [33.06 (95%CI: 28.73-37.40)]. Post-administration compared to baseline assessments (P < 0.05). Additionally, patients reported sustained improvements in psychological well-being and existential distress following psilocybin therapy.
CONCLUSIONS: The findings provided compelling evidence for the potential benefits of psilocybin-assisted therapy in improving quality of life, pain control, and anxiety relief in patients with advanced cancer.

Background and objectives Erectile dysfunction (ED) is a multifactorial disease associated with many medical co-morbidities and risk factors commonly encountered in primary care. Initial management includes lifestyle changes and the treatment of any identifiable conditions. Guidelines exist recommending the assessment and management of sufferers with clear indications for referral to secondary care. With the outbreak of COVID-19, non-urgent medical services, including ED, were suspended, creating a significant waiting list for these patients. The aim of this study was to review the management of men in both primary and secondary care who had been referred to a dedicated ED service.  Materials and methods A retrospective review of men referred to secondary care between June 2018 and April 2021 with ED was undertaken, reviewing whether the guidelines published by the National Institute for Health and Care Excellence (NICE) and GP Notebook for the assessment, initial treatment, and referral were followed by the primary care clinician. A secondary aim was to record the outcome of those men after review in a secondary care dedicated ED clinic. Results One hundred and forty-eight men were reviewed in the ED clinic, with 55 men (37.2%) requiring an intervention that was appropriate to have been delivered in primary care. The majority of those (76.3%) were successfully managed with a phosphodiesterase inhibitor. Of those treated in secondary care, almost 60% required a second-line therapy, such as a vacuum device or the administration of alprostadil, with 14 men (15%) necessitating the surgical implantation of a penile prosthesis. Conclusion With a rise in both the prevalence and incidence of ED, primary care physicians have a pivotal role in the screening and initial assessment of patients with ED, with evidence suggesting that a significant proportion can be successfully managed in this setting.

Inflammatory bowel disease (IBD) has been shown to be connected to a greater possibility of neurologically developed problems, such as autism spectrum disorders (ASDs). However, the proof linking parental IBD with ASD in offspring is inconclusive. Thus, we carried out a meta-analysis and comprehensive review to elucidate such linking. Prior research was identified through reviewing multiple internet-based sources, including Cochrane, Web of Knowledge, Embase, CINAHL, PubMed, and PsycINFO, from 1960 to December 2022. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were determined employing random-effects models, in spite of the I2 statistic measurement of heterogeneity. Prediction intervals (PIs) have been presented to allow for more useful inferences and to indicate the range of genuine effects that might be predicted in future scenarios. Six studies (two case-control studies and four cohort studies) involving 3,200,199 participants were incorporated into the meta-analysis. The pooled RRs of ASDs among offspring of IBD parents were 1.15 (95% CI, 0.92 to 1.45, P = 0.226; I2 = 81.4%, P = 0.003; PI, 0.53-2.62), indicating no significant connection between parental IBD and the likelihood of ASDs in children. Type of IBD, and sex both also yielded no statistically significant results according to subgroup analysis. Our meta-analysis does not provide evidence that parental IBD is connected with the elevated likelihood of ASDs in their children. To confirm these results and understand their underlying mechanisms, additional research with larger sample sizes and improved study designs is required.