Psoriasis is a chronic immune-mediated disease affecting the skin, nails, and/or joints. It is associated with systemic inflammation and may also be linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). The objectives of this study were to determine the overall risk of ASCVD in patients with psoriasis and to evaluate the risk according to ASCVD type and the severity of psoriasis. This was a systematic review and meta-analysis of observational studies reporting the association between psoriasis and one or more of the clinical types of ASCVD. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed, Excerpta Medica Database (EMBASE), Scopus, Bielefeld Academic Search Engine (BASE), and Google Scholar for relevant studies in the English language from the beginning of their records to July 2023. Study selection and data extraction were conducted by four independent reviewers. A total of 21 observational studies (three cross-sectional, one case-control, and 17 cohort) were included in this review, representing a total of 778,049 patients with psoriasis and 16,881,765 control subjects without psoriasis. The included studies had varying degrees of covariate adjustment, and thus, their findings may have been subject to residual confounding. All the meta-analyses used the adjusted effect sizes and were based on the random-effects model. However, the cohort studies were analysed separately from the non-cohort studies (the case-control and cross-sectional studies). There was a significant association between psoriasis and ASCVD (cohort studies: hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.14 to 1.28; I2 = 63%; p < 0.001; non-cohort studies: odds ratio (OR), 1.60; 95% CI, 1.34 to 1.92; I2 = 31%; p = 0.23). Psoriasis was also significantly associated with myocardial infarction (cohort studies: HR, 1.20; 95% CI, 1.10 to 1.31; I2 = 60%; p < 0.001; non-cohort studies: OR, 1.57; 95% CI, 1.15 to 2.15; I2 = 74%; p = 0.05), coronary artery disease (cohort studies: HR, 1.20; 95% CI, 1.13 to 1.28; I2 = 67%; p < 0.001; non-cohort studies: OR, 1.60; 95% CI, 1.34 to 1.92; I2 = 31%; p = 0.23), aortic aneurysm (HR, 1.45; 95% CI, 1.04 to 2.02; I2 = 67%; p = 0.08) but not with ischaemic stroke (HR, 1.14; 95% CI, 0.96 to 1.36; I2 = 44%; p = 0.17). Pooled analysis in terms of the severity of psoriasis showed that both mild (cohort studies: HR, 1.17; 95% CI, 1.08 to 1.26; I2 = 74%; p < 0.001; non-cohort studies: OR, 1.54; 95% CI, 1.25 to 1.90; I2 = 0%; p = 0.50) and severe (cohort studies: HR, 1.43; 95% CI, 1.23 to 1.65; I2 = 65%; p < 0.001; non-cohort studies: OR, 1.65; 95% CI, 1.29 to 2.12; I2 = 25%; p = 0.26) psoriasis were significantly associated with ASCVD. Psoriasis (including mild and severe disease) is associated with an increased risk of ASCVD, including coronary artery disease (CAD) and aortic aneurysm (AA). ASCVD risk assessment and prevention should be prioritised in all adult psoriasis patients. Future observational studies investigating the association between psoriasis and ASCVD should conduct a more comprehensive adjustment of covariates.

UNASSIGNED: Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately controlled by dual long-acting bronchodilator therapy and who have ≥2 exacerbations per year and a blood eosinophil count ≥300cells/µL. ICS therapy is widely prescribed outside guidelines to COPD patients, making ICS withdrawal an important consideration. This systematic review aims to provide an up-to-date analysis of the effect of ICS withdrawal on exacerbation frequency, change in lung function (FEV1) and to determine the proportion of COPD patients who resume ICS therapy following withdrawal.
UNASSIGNED: Randomised controlled trials (RCTs) and observational studies which compared ICS withdrawal with ICS continuation treatment were included. Cochrane Central, Web of Science, CINHAL, Embase and OVID Medline were searched. Risk of bias was assessed using the Cochrane RoB2 tool and the Newcastle-Ottawa Scale. Quality assessment of RCTs was conducted using GRADE. Meta-analysis of post-hoc analyses of RCTs of ICS withdrawal, stratified by blood eosinophil count (BEC), was undertaken.
UNASSIGNED: Ten RCTs (6642 patients randomised) and 6 observational studies (160,029 patients) were included in the results. When ICS was withdrawn and long-acting bronchodilator therapy was maintained, there was no consistent difference in exacerbation frequency or lung function change between the ICS withdrawal and continuation trial arms. The evidence for these effects was of moderate quality. There was insufficient evidence to draw a firm conclusion on the proportion of patients who resumed ICS therapy following withdrawal (estimated range 12-93% of the participants).
UNASSIGNED: Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes.

BACKGROUND: This exploratory review aimed to provide empirical evidence on the definitions of labor, the statistical approaches and measures reported in randomized controlled trials (RCTs) and observational studies measuring the duration of labor.
METHODS: A systematic electronic literature search was conducted using different databases. An extraction form was designed and used to extract relevant data. English, French, and German studies published between 1999 and 2019 have been included. Only RCTs and observational studies analyzing labor duration (or a phase of labor duration) as a primary outcome have been included.
RESULTS: Ninety-two RCTs and 126 observational studies were eligible. No definition of the onset of labor was provided in 21.7% (n = 20) of the RCTs and 23.8% (n = 30) of the observational studies. Mean was the most frequently applied measure of labor duration in the RCTs (89.1%, n = 82), and median in the observational studies (54.8%, n = 69). Most RCTs (83%, n = 76) and observational studies (70.6%, n = 89) analyzed labor duration using a bivariate method, with the t-test being the most frequently applied (45.7% and 27%, respectively). Only 10.8% (n = 10) of the RCTs and 52.4% (n = 66) of the observational studies conducted a multivariable regression: 3 (30%; out of 10) RCTs and 37 (56%; out of 66) observational studies used a time-to-event adapted model.
CONCLUSIONS: This survey reports a lack of agreement with respect to how the onset of labor and phases of labor duration are presented. Concerning the statistical approaches, few studies used survival analysis, which is the appropriate statistical framework to analyze time-to-event data.

BACKGROUND: The accurate assessment of active growth is pivotal for the correction of skeletal malocclusion in growing patients. Cervical vertebral maturation (CVM) staging is easy and devoid of unnecessary radiation, but its inter- and intra-observer agreement is still debatable.
OBJECTIVE: This study aims to assess inter-observer (reliability) and intra-observer agreement (reproducibility) for CVM staging.
METHODS: A comprehensive literature search across five databases up to October 2023 was conducted. Inclusion criteria comprised observational studies that specifically reported intra-rater, inter-rater, or both agreements as their primary objectives for cervical vertebral maturation (CVM) staging. Studies with a sample size exceeding 15 participants were considered for inclusion. After duplicate study selection, data extraction, and risk-of-bias assessment, random-effects meta-analyses of kappa (k)/correlation coefficient (r) and their 95% confidence intervals (CIs) were performed, followed by meta-regressions, sensitivity analyses, and subgroup analyses.
RESULTS: Seventeen observational studies (comprising 1437 lateral cephalograms and 110 assessors) were included. The reliability (8 studies; k=0.62 [95% CI: 0.44, 0.78]) and reproducibility (9 studies; k=0.708 [95% CI: 0.59, 0.82]) were substantial. The inter-observer correlation was almost perfect (in 9 studies; r=0.86 [95% CI: 0.82, 0.89]) while intra-observer correlation was substantial (in 2 studies; r=0.75 [95% CI: 0.62, 0.84]). Tracing of lateral cephalograms significantly increased inter-observer reliability (β=0.29 [0.57, 0.0031]) but cropping and time of assessment (initial vs. follow-up) had no significant impact. The reliability (P<0.001) and reproducibility (P=0.049) of high-quality studies were superior to those observed in low-quality studies.
CONCLUSIONS: Assessment of the CVM staging is accurate and reproducible to a satisfactory level. The accuracy and reproducibility of CVM are higher in studies utilizing traced cephalograms and those with a low-risk of bias.
BACKGROUND: PROSPERO registration (CRD42023468521). Data is openly available at https://doi.org/10.5281/zenodo.10599129.

BACKGROUND: Vitiligo is a disease that affects people of all skin shades and can impact their quality of life. Reliable evidence on the effectiveness and adverse events associated with the recent use of Janus kinase (JAK) inhibitors to treat vitiligo is needed. This protocol for a systematic review and meta-analysis seeks to collect evidence from both randomized controlled trials (RCTs) and observational studies to determine the effectiveness and patient-centered outcomes concerning treatment with JAK inhibitors.
METHODS: We will conduct a systematic review of the literature for RCTs and observational studies that used upadacitinib, ritlecitinib, brepocitinib, ifidancitinib, cerdulatinib, deglocitinib, baricitinib, tofacitinib, and ruxolitinib JAK inhibitors as treatments for vitiligo compared to placebo, no treatment, or combination therapies. We will systematically search from inception in Epistemonikos, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.gov, PsycINFO, Allied and Complementary Medicine Database, Latin American and Caribbean Health Sciences Literature, Web of Science Core Collection, relevant preprint servers, and the gray literature. Ethics approval was not sought as the protocol and systematic review will not involve human participants, but rather summarized and anonymous data from studies. Primary outcomes include quality of life, percentage repigmentation, decreased vitiligo within 1 year or more, lasting repigmentation after a 2-year follow-up, cosmetic acceptability of repigmentation and tolerability or burden of treatment, and adverse events. Secondary outcomes are patient and study characteristics. We will include full-text articles, preprints, and clinical trial data in any language and all geographic regions. For data sources unavailable in English, we will obtain translations from global collaborators via the Cochrane Engage network. We will exclude articles for which sufficient information cannot be obtained from the authors of articles and systematic reviews. At least two investigators will independently assess articles for inclusion and extract data; reliability will be assessed before subsequent selection and data extraction of remaining studies. The risk of bias and certainty of evidence with Grading of Recommendations Assessment, Development, and Evaluation guidelines will be assessed independently by at least two investigators. We will estimate treatment effects by random-effects meta-analyses and assess heterogeneity using I2. Data that cannot be included in the meta-analysis will be reported narratively using themes.
CONCLUSIONS: The proposed systematic review and meta-analysis describe the methods for summarizing and synthesizing the evidence on the effectiveness and patient-centered outcomes concerning the treatment of vitiligo with JAK inhibitors that were recently approved for this indication. To disseminate further the results of our systematic review, we plan to present them at international conferences and meetings. Our findings will provide robust evidence to facilitate decision-making at the policy or practitioner level.
BACKGROUND: PROSPERO CRD42023383920.

BACKGROUND: The diagnosis of peripheral arterial disease (PAD) is commonly applied for symptoms related to atherosclerotic obstructions in the lower extremity, though its clinical manifestations range from an abnormal ankle-brachial index to critical limb ischemia. Subsequently, management and prognosis of PAD vary widely with the disease stage. A critical aspect is how this variation is addressed in administrative database-based studies that rely on diagnosis codes for case identification. The objective of this scoping review is to inventory the identification strategies used in studies on PAD that rely on administrative databases, to map the pros and cons of the International Classification of Diseases (ICD) codes applied, and to propose a first outline for a consensus framework for case identification in administrative databases.
METHODS: Registry-based reports published between 2010 and 2021 were identified through a systematic PubMed search. Studies were subcategorized on the basis of the expressed study focus: claudication, critical limb ischemia, or general peripheral arterial disease, and the ICD code(s) applied for case identification mapped.
RESULTS: Ninety studies were identified, of which 36 (40%) did not specify the grade of PAD studied. Forty-nine (54%) articles specified PAD grade studied. Five (6%) articles specified different PAD subgroups in methods and baseline demographics, but not in further analyses. Mapping of the ICD codes applied for case identification for studies that specified the PAD grade studied indicated a remarkable heterogeneity, overlap, and inconsistency.
CONCLUSIONS: A large proportion of registry-based studies on PAD fail to define the study focus. In addition, inconsistent strategies are used for PAD case identification in studies that report a focus. These findings challenge study validity and interfere with inter-study comparison. This scoping review provides a first initiative for a consensus framework for standardized case selection in administrative studies on PAD. It is anticipated that more uniform coding will improve study validity and facilitate inter-study comparisons.

The objective of this scoping review is to evaluate the updated evidence on the consumption of alcohol and health outcomes regarded as relevant for the Nordic and Baltic countries, including cardiovascular disease, cancer, and all-cause mortality. It is based on the previous Nordic Nutrition Recommendations of 2012 and relevant papers published until 31 May 2021. Current evidence from mainly observational epidemiological studies suggests that regular, moderate alcohol consumption may confer protective effects against myocardial infarction (MI) and type 2 diabetes. Mendelian randomization analyses do not fully support these findings, possibly because these analyses may fail to identify low alcohol intake. For several cancers, it is not possible to set any safe limit. All-cause mortality is not increased with light to moderate alcohol intake in middle-aged and older adults who do not engage in binge drinking. Total abstinence is associated with the lowest risk of mortality in young adults. Observational studies on alcohol consumption are hampered by a number of inherent methodological issues such as ascertainment of alcohol intake, selection of appropriate exposure groups, and insufficient control of confounding variables, colliders, and mediators. It should also be emphasized that there is a socio-economic contribution to the alcohol-health axis with a stronger detrimental effect of alcohol in the lower social classes. The above issues contribute to the complexity of unravelling the causal web between alcohol, mediators, confounders, and health outcome.

BACKGROUND: Hepatocellular carcinoma (HCC) is a disease demonstrating increasing morbidity and mortality, especially in patients with chronic viral hepatitis. Studies have shown that aspirin can reduce the incidence of liver cancer; however, the degree of benefit in patients with viral hepatitis is unclear. This study focused on the association between aspirin use and HCC risk in patients with chronic viral hepatitis.
METHODS: A systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from the earliest available date to December 16, 2023. The primary outcome was HCC incidence, and the secondary outcome was gastrointestinal bleeding. The results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analyses were performed by using random or fixed-effects models based on the heterogeneity assessed via the I2 statistic.
RESULTS: A total of 13 articles (303,414 participants and 14,423 HCC patients) were included in the analysis. The incidence of HCC in aspirin users was lower than that in non-aspirin users (HR 0.75; 95% CI, 0.68-0.83; P < 0.001; I2 = 90.0%). Subgroup analysis further showed that this effect may be more obvious in HCV patients, non-cirrhotic patients, patients with statins, and long-term aspirin users, but it may have the risk of gastrointestinal bleeding (HR 1.13; 95% CI, 1.07-1.20; P = 0.906; I2 = 0.0%).
CONCLUSIONS: Our meta-analysis shows that in patients with chronic viral hepatitis, aspirin use is associated with a significantly reduced risk of liver cancer, but attention should be paid to the possible risk of gastrointestinal bleeding, and this conclusion needs further validation in the future.

BACKGROUND: Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting.
METHODS: Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively.
RESULTS: The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (- 1.71 [- 2.74, - 0.67]; p = 0.001), SBP (- 6.35 [- 10.17, - 2.53]; p = 0.001), HbA1c levels (- 1.48 [- 1.75, - 1.21]; p < 0.00001), and FPG (- 2.27 [- 2.78, - 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant.
CONCLUSIONS: This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to-action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.

OBJECTIVE: The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring.
METHODS: PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I2 statistic for heterogeneity and publication bias was calculated.
RESULTS: Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I2 = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I2 = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I2 = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I2 = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I2 = 39.4%).
CONCLUSIONS: These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.