Summary Risk Ratios Research Articles

Cenobamate add-on therapy for drug-resistant focal epilepsy.

Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs. To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies. RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs. Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table. We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate. Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.

P-676 Obstetric and perinatal outcomes in women with Turner Syndrome: A systematic review and meta-analysis

Abstract Study question What is the pooled risk of adverse obstetric and neonatal outcomes in pregnancies in women with Turner Syndrome (TS)? Summary answer TS women experience high rates of adverse outcomes. Risks are increased in egg donation pregnancies and multiple pregnancies compared to singleton spontaneous pregnancies. What is known already TS affects 1 in 2,000 live female births. The 2017 ‘Clinical Practice Guidelines for the Care of Girls and Women with Turner Syndrome’ acknowledges women with TS are at increased risk of adverse obstetric and perinatal outcomes. Several retrospective cohort studies reporting obstetric and neonatal outcomes in TS pregnancies have been published in recent years. However, these studies are often limited to a single centre cohort, within one country and thus increasing risk of bias. Overall pooled risk estimates for each outcome have yet to be reported. Study design, size, duration A prospectively registered systematic review and meta-analysis was conducted and reported in line with PRISMA guidelines. Overall pooled rates of each outcome Is reported with 95% confidence interval. Pooled risk ratios comparing spontaneous and egg donation pregnancies are also reported. A comparative meta-analysis reports on dichotomous outcomes using summary risk ratio (RR) with 95%CI and on continuous outcomes using weighted mean difference (WMD) with 95%CI. Publication bias was assessed using the Newcastle-Ottawa Scale. Participants/materials, setting, methods A comprehensive literature search was undertaken. Eligibility screening was conducted by 2 independent reviewers. Studies were limited to English language with no time limit. Case reports were excluded. 30 studies reporting obstetric or perinatal outcomes in pregnancies of women with TS were included in the analysis. Outcome data was extracted and tabulated using a standard proforma. Main results and the role of chance 1724 pregnancies were included. Pooled risks: Obstetric outcomes: caesarean section (62.8%)(95%CI:57-76%), pregnancy-associated hypertensive disorders (21%)(95%CI:13-29%), pre-eclampsia (10%)(95%CI:6-14%),gestational diabetes mellitus (6.0%)(95%CI:4-8%), aortic dissection (1.1%)(95%CI:0-2%), intrahepatic cholestasis of pregnancy (4.6%)(95%CI:0-7%), post-partum haemorrhage (17.9%)(95%CI:-3-37%), and maternal mortality (0.3%)(95%CI:0-1%). Perinatal outcomes: prematurity (14.1%)(95%CI:8-18%), low birthweight (25.1%)(95%CI:12-23%), and perinatal mortality (1.2%)(95%CI:0-1%). Egg-donation pregnancies yield significantly higher rates of: caesarean section (82.8% vs. 55.7%) (RR1.49) (95% CI:1.27-1.76), pregnancy-associated hypertensive disorder (33.0% vs 12.9%: p=0.001), pre-eclampsia (16.9% vs 8.2%: p=0.0023), gestational hypertension (17.9% vs 0.0%: p=0.082), low-birthweight (43.0% vs 1.9%: p<0.001) and preterm birth (17.5% vs 0.0%: p<0.001) than spontaneous pregnancies. Multiple pregnancies resulted in high rates of prematurity (70.0%), low birth-weight (73.3%) and pregnancy-associated hypertensive disorders (60.9%). Limitations, reasons for caution Most studies were retrospective and included cases from many years ago so may not be reflective of current obstetric practice and improved care. Most studies were geographically clustered in Europe and North America. Estimations of risk may therefore not be generalisable to other ethnicities and middle and lower income countries Wider implications of the findings This study quantifies the risk of adverse outcomes in pregnancies in women with TS. Risk is increased further in egg donation pregnancies and strategies should aim to screen and prevent complications, particularly hypertensive disorders of pregnancy. Multiple pregnancy should be avoided through use of single embryo transfer. Trial registration number N/a

Arterial hypertension associated with PARPi: A meta-analysis of 41 placebo randomized controlled trials combined with a World Health Organization's pharmacovigilance study.

Arterial hypertension has been recently reported from randomized controlled trials (RCTs) assessing poly (ADP-ribose) polymerase inhibitor (PARPi). In a context of increasing use of PARPi, it is crucial to properly assess risk and incidence of this adverse event for clinical practice. We performed a systematic review and meta-analysis in MEDLINE, Cochrane CENTRAL and ClinicalTrials.gov up to January 4, 2023 with an ongoing surveillance up to June 7, 2023. RCTs comparing PARPi to placebo in adult patients with solid tumors were included if hypertension was reported. The primary outcome was the summary risk ratio (RR, with 95% CIs) of any hypertension of PARPi class in placebo RCTs. Secondary outcomes were the summary risk and incidence of hypertension of each individual PARPi. To provide clinical features of PARPi-associated hypertension, we independently queried the WHO's pharmacovigilance database, up to September 1, 2022. In total, 41 placebo RCTs (n = 15 264 adult patients) were included. PARPi class was not associated with an increased risk of hypertension compared with placebo. In individual analyses, the risk of hypertension was lower with olaparib than placebo (RR 0.77 [95% CI: 0.68-0.86], P < 0.01; I2= 19%, χ2 P = 0.26). Niraparib monotherapy increased the risk of any (RR 2.84 [95% CI: 1.76-4.57], P < 0.01; I2= 66%, χ2 P = 0.01) hypertension with a summary incidence of 19.87% (95% CI: 15.23-25.50). In real-life setting, niraparib-associated hypertension occurs within 20 days and was serious in 66%. Co-prescription of at least one antihypertensive or therapy-induced hypertension was reported in 20.5% or 14.4% of cases, respectively. In a context of extensive assessment of niraparib in combination, these data reinforce the need of a close monitoring of this adverse event to preserve its clinical benefit on patients' survival.

Fluoride Exposure and Skeletal Fluorosis: a Systematic Review and Dose-response Meta-analysis.

We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling. Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated. We included twenty-three studies in the meta-analysis. When comparing the highest versus the lowest fluoride category, the summary risk ratio (RR) for SF prevalence was 2.05 (95% CI 1.60; 2.64), with a value of 2.73 (95% CI 1.92; 3.90) for drinking water and 1.40 (95% CI 0.90; 2.17) for urinary fluoride. The RR by the risk of bias (RoB) was 2.37 (95% CI 1.56; 3.58) and 1.78 (95% CI 1.34; 2.36) for moderate and high RoB studies, respectively. The dose-response curve based on a one-stage cubic spline regression model showed an almost linear positive relation between exposure and SF occurrence starting from relatively low concentrations up to 5 mg/L and 2.5 mg/L, respectively, for water and urinary fluoride, with no substantial increase above this threshold. The RR for developing moderate-severe forms increases at 5.00 mg/L and 2.5 mg/L of water and urinary fluoride, respectively. Better-quality studies are needed to confirm these results, but greater attention should be given to water fluoride levels to prevent SF, in addition to the other potential adverse effects of fluoride exposure.

Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis.

Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD. We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model. 56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low. Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.

Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis.

Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR=1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR=1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR=1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR=1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR=0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR=1.09, 95% CI: 1.00-1.20), ER- (RR=1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR=1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2-positive BCa was also positive (RR=1.21, 95% CI: 0.52-2.82), but the CI was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.

Cervical cerclage for prevention of preterm birth and adverse perinatal outcome in twin pregnancies with short cervical length or cervical dilatation: A systematic review and meta-analysis.

The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies. Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI [0.59, 0.91], p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI [0.57, 0.84], p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% [CI 0.43, 0.67], 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI [0.23, 0.97], p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% [CI 0.99, 3.66], p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI [0.25, 0.60], p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI [0.53, 0.90], p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI [0.58, 0.95], p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI [0.57, 0.80], p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low. Emergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.

Efficacy and safety of once-daily prolonged-release tacrolimus versus twice-daily tacrolimus in kidney transplant recipients: A meta-analysis and trial sequential analysis.

Kidney transplantation is the most important treatment for end-stage renal disease. Immunosuppressive therapies can prevent acute rejection for kidney transplant recipients. Tacrolimus is usually administered to prevent graft rejection after transplantation. Previous studies have indicated that once-daily tacrolimus may improve medication adherence. Therefore, this meta-analysis aimed to compare clinical outcomes between once-daily and twice-daily tacrolimus in de novo renal transplant patients. Eligible studies were identified from the Cochrane Library Database, PubMed, and Embase until July 2022. Those randomized controlled trials (RCTs) evaluating once-daily versus twice-daily tacrolimus formulations in de novo renal transplantation were included. A summary risk ratio (RR) and standardized mean difference (SMD) with the 95% confidence interval (CI) were estimated using a random-effects model. In total, nine RCTs were included. There were no differences in biopsy-confirmed acute rejection rates between patients with once-daily and those with twice-daily tacrolimus (RR, 0.91; 95% CI, 0.73-1.13) in 12 months. Regarding renal function, there was no significant difference between the once-daily and twice-daily tacrolimus groups (SMD, -0.03; 95% CI, -0.12 to 0.07). In addition, the risk of graft failure, death, and adverse events in the first year was similar for the once-daily and twice-daily tacrolimus groups. Our major findings suggest that de novo renal transplantation recipients receiving once-daily tacrolimus immediately after transplantation have comparable efficacy and safety with those recipients who received twice-daily tacrolimus. Therefore, once-daily tacrolimus medication can be an alternative for de novo renal transplantation recipients.

Adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations and cancer risk: Asystematic review and meta-analysis.

The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle-based guidelines that aim to reduce cancer risk. A systematic review and meta-analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted. MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta-analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1-point increment) and categorical (highest vs. lowest score category) variable using random-effects models were estimated. Eighteen studies (11 cohort; seven case-control) were included investigating incidence of breast (n=7), colorectal (n=5), prostate (n=2), lung (n=2), pancreatic (n=1), endometrial (n=1), unknown primary cancer (n=1), chronic lymphocytic leukemia (n=1), and overall (any) cancer (n=1). The summary risk ratio per 1-point increment in adherence score was 0.89 (95% CI, 0.85-0.93; I2 =76.5%; n=7) for breast cancer, 0.88 (95% CI, 0.84-0.91; I2 =26.2%; n=4) for colorectal cancer, and 0.92 (95% CI, 0.86-0.98, I2 =66.0%; n=2) for lung cancer. There were no significant associations with prostate or other cancers. Meta-analysis results using categorical adherence score variables were consistent with these findings. Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted. CRD42022313327.

Suicide and depression in former contact sports participants: population-based cohort study, systematic review, and meta-analysis.

Former participants in sports characterised by low intensity repetitive head impact appear to have elevated rates of later dementia, but links with other psychological health outcomes such as depression and suicide are uncertain. We quantified the occurrence of these endpoints in former contact sports athletes against general population controls using new data from a cohort study and a meta-analysis. The cohort study comprised 2004 retired male athletes, who had competed internationally as amateurs for Finland across a range of sports, and 1385 general population controls. All study members were linked to mortality and hospitalisation registries. In the PROSPERO-registered systematic review (CRD42022352780), we searched PubMed and Embase to October 31 2022 for cohort studies that reported standard estimates of association and precision. Study-specific estimates were aggregated in a random-effect meta-analysis. The Newcastle-Ottawa Scale was used to appraise the quality of each study. In survival analyses of the Finnish cohort data, former boxers (depression: hazard ratio 1.43 [95% CI 0.73, 2.78]; suicide: 1.75 [0.64, 4.38]), Olympic-style wrestlers (depression: 0.94 [0.44, 2.00]; suicide: 1.60 [0.64, 3.99]), and soccer players (depression: 0.62 [0.26, 1.48]; suicide: 0.50 [0.11, 2.16]) did not have statistically higher rates of major depressive disorder or suicide at follow-up relative to controls. In the systematic review, 7 cohort studies met inclusion criteria. After aggregating results with the Finnish cohort, retired soccer players appeared to have a lower risk of depression (summary risk ratio: 0.71 [0.54, 0.93]) relative to general population controls, while the rate of suicide was statistically the same across groups (0.70 [0.40, 1.23]). Past participation in American football seemed to be associated with some protection against suicide (0.58 [0.43, 0.80]) but there were insufficient studies of depression in this sport to facilitate aggregation. The aggregation of results from the soccer and American football studies showed directionally consistent relationships and there was no indication of inter-study heterogeneity (I2=0%). Based on a small cluster of studies exclusively comprising men, retired soccer players had a lower rate of later depression and former American football players had a lower risk of suicide relative to comparator groups. Whether these findings are generalisable to women requires testing. The preparation of this manuscript was unfunded.

Food groups and urologic cancers risk: a systematic review and meta-analysis of prospective studies.

To assess the association between 12 food groups intake and the risk of urologic cancers. We scanned PubMed and Web of Science databases up to April 1st, 2023, and 73 publications met the inclusion criteria in the meta-analysis. We used a random effects model to estimate the summary risk ratios (RRs) and 95% confidence intervals (95% CI). In the linear dose-response meta-analysis, an inverse association was found between each additional daily 100 g of fruits [RR: 0.89, 95%CI = (0.83, 0.97)], 100 g of vegetables [RR: 0.92, 95%CI = (0.85, 0.99)], 12 g of alcohol [RR: 0.91, 95%CI = (0.88, 0.94)] and 1 cup of coffee [RR: 0.95, 95%CI = (0.83, 0.97)] intake and the risk of renal cell carcinoma. Conversely, each additional daily 100 g of red meat intake was positively associated with renal cell carcinoma [RR: 1.41, 95%CI = (1.03, 2.10)]. Inverse associations were observed between each additional daily 50 g of egg [RR: 0.73, 95%CI = (0.62, 0.87)] and each additional daily 1 cup of tea consumption and bladder cancer risk [RR: 0.97, 95%CI = (0.94, 0.99)]. There were no significant associations for nonlinear dose-response relationships between 12 food groups and urological cancers. Our meta-analysis strengthens the evidence that appropriate intake of specific food groups, such as fruits, vegetables, alcohol, tea, and coffee, is associated with the risk of renal cell carcinoma or bladder cancer. More studies are required to fill the knowledge gap on the links between various food groups and urologic cancers because the evidence was less credible in this meta-analysis. This study was registered on PROSPERO (CRD42022340336).

Anticoagulation use in perioperative atrial fibrillation after noncardiac surgery: a systematic review and meta-analysis

Perioperative atrial fibrillation is associated with an increased risk of stroke, myocardial infarction, and death after noncardiac surgery. Anticoagulation therapy is effective for stroke prevention in nonsurgical atrial fibrillation, but its efficacy and safety in perioperative atrial fibrillation are unknown. We searched MEDLINE, EMBASE, and CENTRAL from database inception until January 2022. We included studies comparing anticoagulation versus no anticoagulation use in patients with perioperative atrial fibrillation after noncardiac surgery. Our study outcomes included stroke ± systemic embolism, bleeding, mortality, myocardial infarction, and venous thromboembolism. We pooled studies using fixed-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable-adjusted results. Seven observational studies but no randomised trials were included. Of the 27,822 patients, 29.1% were prescribed therapeutic anticoagulation. Anticoagulation use was associated with a lower risk of stroke ± systemic embolism (RR 0.73; 95% CI, 0.62-0.85; I2= 81%; 3 studies) but a higher risk of bleeding (RR 1.14; 95% CI, 1.04-1.25; 1 study). There was a lower risk of mortality associated with anticoagulation use (RR 0.45; 95% CI, 0.40-0.51; I2= 80%; 2 studies). There was no difference in the risk of myocardial infarction (RR 2.19; 95% CI, 0.97-4.96; 1 study). The certainty of the evidence was very low across all outcomes. Anticoagulation is associated with a reduced risk of stroke and death but an increased risk of bleeding. The quality of the evidence is very poor. Randomised trials are needed to better determine the effects of anticoagulation use in this population.

Epidemiology of depression and suicidal ideation in patients with psoriasis: A meta-analysis of prospective cohort studies

Background: Psoriasis is an immune-mediated inflammatory, chronic, recurrent skin disease associated with a high risk of developing psychiatric disorders, especially depression and suicidal ideation, leading to functional disability and poor quality of life. Objective: To comprehensively review and assess the epidemiologic association between psoriasis and the risk ratios (RRs) of depression or suicidal ideation. Methods: Five databases (PubMed, Wanfang Database, CNKI, The Cochrane Library, and EMBASE) were searched for prospective cohort studies on the prevalence of depression and/or suicidal ideation in patients with psoriasis updated to 2 February 2023. Two independent reviewers evaluated and extracted the data, which were then pooled into a summary RR with corresponding 95% confidence interval (CI) using random-effects models in Stata/MP14.0. Results: Sixteen cohort studies comprising 1,166,840 patients with psoriasis and 3,294,205 controls were eligible for the final analysis. The pooled RR for depression was 1.43 (95% CI = 1.13–1.81) in patients with psoriasis and1.55 (95% CI = 1.40–1.71) in patients with psoriatic arthritis. In the subgroup analysis, Asian patients with psoriasis (RR=1.38, 95% CI =1.17–1.63) had a lower pooled RR for depression than non-Asian patients (RR=1.45, 95% CI = 1.07–1.97), and patients with moderate to severe psoriasis (RR=1.69, 95% CI = 1.15–2.50) showed a higher RR for depression than patients with mild psoriasis (RR=1.60, 95% CI= 1.06–2.42). We also found no increase in the RR for suicidal ideation among people with psoriasis (RR=1.25, 95% CI =0.95–1.65). Conclusions: Patients with psoriasis are at increased risk of depression. Among patients with psoriasis, those with psoriatic arthritis, those who are non-Asian, and those with moderate to severe psoriasis are at higher risk for depression. However, the available evidence does not support an association between psoriasis and suicidal ideation.

The Association Between PCSK9 Inhibitor Use and Sepsis: A Systematic Review and Meta-Analysis of 20 Double-Blind, Randomized, Placebo-Controlled Trials

ObjectiveThe aim of this study was to determine the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor use on incident sepsis and other severe infections. MethodsWe searched PubMed, EMBASE, CENTRAL, and ClinicalTrial.gov up to September 14, 2021, for double-blind, placebo-controlled randomized trials of alirocumab, evolocumab, or inclisiran with >100 participants in each arm and report of serious adverse events related to infection. Data were synthesized with the fixed-effect Mantel-Haenszel model to generate risk ratios (RRs) with 95% confidence intervals (CIs) of each outcome for PCSK9 inhibitor versus placebo. Main outcome was sepsis. Other outcomes were total severe infections, severe bacterial and viral infections, and severe organ system-specific infections including respiratory tract, gastrointestinal, and genitourinary tract infections. ResultsA total of 20 studies of 64,984 participants were included (alirocumab: n = 7; evolocumab: n = 9; inclisiran: n = 4). Sepsis was reported in 292 (0.51%) participants from 11 trials (PCSK9 inhibitor 0.47%; placebo 0.56%). PCSK9 inhibitor use was not associated with risk of sepsis compared with placebo (Summary RR: 0.85, 95% CI: 0.67-1.07, P = .16); nor was it associated with any severe infection (0.96, 95% CI: 0.89-1.03), severe bacterial (0.96, 95% CI: 0.81-1.14) and viral infections (1.01, 95% CI: 0.77-1.33); nor with any severe organ system-specific infection (all P values >.05). The between-study heterogeneity in all analyses was small. ConclusionThere was neither a beneficial nor a harmful association between PCSK9 inhibitors and risk of sepsis or severe infections. These findings provide reassurance regarding the safety of PCSK9 inhibitors in patients who are concerned about potential drug side effects related to infections.

Parental smoking and risk of hypospadias: An updated meta-analysis of observational studies.

Inconsistent relationships have been shown between cigarette smoking and hypospadias in offspring. The purpose of this study was to summarize epidemiological evidence to evaluate the relationship between parental smoking and the risk of hypospadias. Up until October 2022, PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for qualified research. The summary RRs and 95% CIs were calculated using either a fixed-effects or a random-effects model. There were subgroup analyses undertaken to identify potential sources of heterogeneity. 44 studies with 16,637,830 participants were included in our meta-analysis. Overall, maternal active smoking [risk ratio (RR) = 0.94; 95% confidence interval (CI): 0.90-0.99; P < 0.01] was significantly associated with the risk of hypospadias. And neither paternal smoking (RR = 1.00; 95% CI: 0.86-1.15) nor maternal passive smoking (RR = 0.91; 95% CI: 0.60-1.23) was associated with the risk of hypospadias. Our study discovered an association between maternal active smoking and a decreased risk of hypospadias, which may be due to the effect of smoking on androgen. However, as numerous studies have proved that cigarette smoking during pregnancy increases the risk of overall birth abnormalities in offspring, quitting cigarettes before pregnancy positively influences the health of offspring and should be advocated worldwide. [www.crd.york.ac.uk/prospero], identifier [CRD42022319378].

Impact of remote vital sign monitoring on health outcomes in acute respiratory infection and exacerbation of chronic respiratory conditions: systematic review and meta-analysis.

Our aim was to investigate the effectiveness of virtual wards on health outcomes in patients with acute respiratory infection. We searched four electronic databases from January 2000 to March 2021 for randomised controlled trials (RCTs). We included studies in people with acute respiratory illness or an acute exacerbation of a chronic respiratory illness, where a patient or carer measured vital signs (oximetry, blood pressure, pulse) for initial diagnosis and/or asynchronous monitoring, in a person living in private housing or a care home. We performed random-effects meta-analysis for mortality. We reviewed 5834 abstracts and 107 full texts. Nine RCTs were judged to be relevant for inclusion, in which sample sizes ranged from 37 to 389 (total n=1627) and mean ages ranged between 61 and 77 years. Five were judged to be at low risk of bias. Five RCTs had fewer hospital admissions in the intervention (monitoring) group, out of which two studies reported a significant difference. Two studies reported more admissions in the intervention group, with one reporting a significant difference. We were unable to perform a meta-analysis on healthcare utilisation and hospitalisation data due to lack of outcome definition in the primary studies and variable outcome measurements. We judged two studies to be at low risk of bias. The pooled summary risk ratio for mortality was 0.90 (95% CI 0.55-1.48). The limited literature for remote monitoring of vital signs in acute respiratory illness provides weak evidence that these interventions have a variable impact on hospitalisations and healthcare utilisation, and may reduce mortality.

Caring contacts for suicide prevention: A systematic review and meta-analysis.

Caring Contacts (CC), a low-cost intervention originally designed and tested by Jerome Motto in 1976, remains one of the few strategies to demonstrate efficacy in the prevention of suicide deaths. Interest in CC has increased steadily over the last several years in tandem with rising U.S. suicide rates and the acceleration of suicide prevention initiatives. There have been several efforts to design interventions modeled after Motto's strategy, and the recent publication of additional large-scale randomized controlled trials (RCTs) in alignment with the intent of Motto's original model afford an opportunity to systematically review efficacy findings. The current systematic review provides an updated and focused analysis of the evidence supporting the efficacy of CC. A systematic literature search of MEDLINE, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov was conducted, and PRISMA, Cochrane, and GRADE guidelines were followed. Of 2,746 abstracts reviewed, 13 publications, comprising six randomized controlled trials (RCTs) met inclusion criteria. The studies encompassed 6,218 participants across four countries and military, veteran, and civilian health care systems. The primary outcome was suicide mortality; secondary outcomes were suicide attempts and emergency department (ED) presentations/hospitalizations. The DerSimonian-Laird random-effects univariate meta-analysis was used to estimate summary effect sizes and evaluate statistical heterogeneity. Summary risk ratio estimates ranged from 0.57 to 1.29 across outcomes and time points; most estimates indicated a protective effect. For suicide deaths and ED presentations/hospitalization, interval estimates at 1-year postrandomization were consistent with either an increase or a decrease in risk. A protective effect was observed for suicide attempts at 1-year postrandomization. Implications and methodological recommendations for future work in this area reviewed and discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Dietary Factors and All-Cause Mortality in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Prospective Observational Studies.

Type 2 diabetes is a major health concern associated with mortality. Diet may influence the progression of diabetes; however, systematic reviews are lacking. This study systematically summarized the evidence on diet and all-cause mortality in individuals with type 2 diabetes. PubMed and Web of Science were searched until June 2022. Prospective observational studies investigating dietary factors in association with all-cause mortality in individuals with type 2 diabetes were selected. We identified 107 studies. Moderate certainty of evidence was found for inverse associations of higher intakes of fish (summary risk ratios per serving/week: 0.95; 95% CI 0.92, 0.99; n = 6 studies), whole grain (per 20 g/day: 0.84; 95% CI 0.71, 0.99; n = 2), fiber (per 5 g/day: 0.86; 95% CI 0.81, 0.91; n = 3), and n-3 polyunsaturated fatty acids (per 0.1 g/day: 0.87; 95% CI 0.82, 0.92; n = 2) and mortality. There was low certainty of evidence for inverse associations of vegetable consumption (per 100 g/day: 0.88; 95% CI 0.82, 0.94; n = 2), plant protein (per 10 g/day: 0.91; 95% CI 0.87, 0.96; n = 3), and for positive associations of egg consumption (per 10 g/day: 1.05; 95% CI 1.03, 1.08; n = 7) and cholesterol intake (per 300 mg/day: 1.19; 95% CI 1.13, 1.26; n = 2). For other dietary factors, evidence was uncertain or no association was observed. Higher intake of fish, whole grain, fiber, and n-3 polyunsaturated fatty acids were inversely associated with all-cause mortality in individuals with type 2 diabetes. There is limited evidence for other dietary factors, and, thus, more research is needed.

The cure rate of 10-day bismuth-containing quadruple therapy for Helicobacter pylori eradication is equivalent to 14-day: a systematic review and meta-analysis.

Helicobacter pylori (H. pylori) infection is a major cause of duodenal ulcers, gastric ulcers, and gastric cancer. However, the optimal duration for H. pylori eradication therapy remains controversial. Most studies have mainly focused on triple therapy, and there is insufficient research on bismuth-containing quadruple therapy. The aim of this study was to compare the clinical effect of the 10-day bismuth-containing quadruple treatment regimen with the 14-day regime in eradicating H. pylori. We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials published in English until May 2022 according to the eligibility criteria. Summary risk ratios (RRs) and 95% confidence intervals (CIs) for eradication rates, adverse effects, and compliance were calculated for included studies. Four studies, involving 1173 patients, were eligible for inclusion. The eradication rate was similar in the 10-day treatment group and the 14-day treatment group in the intention-to-treat analysis (RR 0.97, 95% CI 0.93 to 1.01). Meanwhile, the incidence of adverse effects was lower in patients who received 10days of treatment than in those who received 14days of treatment and patients' compliance was almost the same between two groups. Compared to the 14-day bismuth-containing quadruple regimens, 10-day regimens had similar efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and well-tolerated and should be recommended for H. pylori infection.

Physical Activity and Risk of Major Diabetes-Related Complications in Individuals With Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

Physical activity is a cornerstone in diabetes management; however, evidence synthesis on the association between physical activity and long-term diabetes-related complications is scarce. To summarize and evaluate findings on physical activity and diabetes-related complications, we conducted a systematic review and meta-analysis. We searched PubMed, Web of Science, and the Cochrane Library for articles published up to 6 July 2021. We included prospective studies investigating the association between physical activity and incidence of and mortality from diabetes-related complications, i.e., cardiovascular disease (CVD), coronary heart disease, cerebrovascular events, heart failure, major adverse cardiovascular events, and microvascular complications such as retinopathy and nephropathy, in individuals with diabetes. Study characteristics and risk ratios with 95% CIs were extracted. Random-effects meta-analyses were performed, and the certainty of evidence and risk of bias were evaluated with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools. Overall, 31 studies were included. There was moderate certainty of evidence that high versus low levels of physical activity were inversely associated with CVD incidence, CVD mortality (summary risk ratio 0.84 [95% CI 0.77, 0.92], n = 7, and 0.62 [0.55, 0.69], n = 11), and microvascular complications (0.76 [0.67, 0.86], n = 8). Dose-response meta-analyses showed that physical activity was associated with lower risk of diabetes-related complications even at lower levels. For other outcomes, similar associations were observed but certainty of evidence was low or very low. Limitations include residual confounding and misclassification of exposure. Physical activity, even below recommended amounts, was associated with reduced incidence of diabetes-related complications.