Observational Studies Research Articles

Different effects of 24 dietary intakes on gastroesophageal reflux disease: A mendelian randomization

BACKGROUND In observational studies, dietary intakes are associated with gastroesophageal reflux disease (GERD). AIM To conduct a two-sample mendelian randomization (MR) analysis to determine whether those associations are causal. METHODS To explore the relationship between dietary intake and the risk of GERD, we extracted appropriate single nucleotide polymorphisms from genome-wide association study data on 24 dietary intakes. Three methods were adopted for data analysis: Inverse variance weighting, weighted median methods, and MR-Egger's method. The odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the causal association between dietary intake and GERD. RESULTS Our univariate Mendelian randomization (UVMR) results showed significant evidence that pork intake (OR, 2.83; 95%CI: 1.76-4.55; P = 1.84 × 10–5), beer intake (OR, 2.70, 95%CI: 2.00-3.64; P = 6.54 × 10–11), non-oily fish intake (OR, 2.41; 95%CI: 1.49-3.91; P = 3.59 × 10–4) have a protective effect on GERD. In addition, dried fruit intake (OR, 0.37; 95%CI: 0.27-0.50; 6.27 × 10–11), red wine intake (OR, 0.34; 95%CI: 0.25-0.47; P = 1.90 × 10-11), cheese intake (OR, 0.46; 95%CI: 0.39-0.55; P =3.73 × 10-19), bread intake (OR, 0.72; 95%CI: 0.56-0.92; P = 0.0009) and cereal intake (OR, 0.45; 95%CI: 0.36-0.57; P = 2.07 × 10-11) were negatively associated with the risk of GERD. There was a suggestive association for genetically predicted coffee intake (OR per one SD increase, 1.22, 95%CI: 1.03-1.44; P = 0.019). Multivariate Mendelian randomization further confirmed that dried fruit intake, red wine intake, cheese intake, and cereal intake directly affected GERD. In contrast, the impact of pork intake, beer intake, non-oily fish intake, and bread intake on GERD was partly driven by the common risk factors for GERD. However, after adjusting for all four elements, there was no longer a suggestive association between coffee intake and GERD. CONCLUSION This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD, providing new insights for the treatment and prevention of GERD.

Efficacy and safety of intravenous immunoglobulin therapy in systemic sclerosis: a systematic review.

Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc. The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies. From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash. Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations.

Overcoming geographical and socioeconomic limitations in colorectal cancer screening

Despite colorectal cancer’s (CRC) high global incidence, residents of low- and middle- income countries, as well as low-income minorities in advanced economies have low screening rates. Observational studies demonstrate that in these groups higher incidence of CRC is observed, yet screening rates remain low for consistent reasons. Low income, low educational background, and lack of awareness in combination with inadequate social security of certain population groups impede access and compliance rates to CRC screening. On the other hand, despite the global availability of multiple screening approaches (colonoscopy, sigmoidoscopy, faecal occult blood test, faecal immunochemical test, computed tomography-colonography, etc. ) with proven diagnostic validity, many low-income countries still lack established screening programs. The absence of screening guidelines in these countries along with the heterogeneity of guidelines in the rest of the world, demonstrate the need for global measures to tackle this issue comprehensively. An essential step forward is to develop a global approach that will link specific elements of screening with the incidence and available resources in each country, to ensure the achievement of at least a minimum screening program in low-income countries. Utilizing cheaper, cost-effective techniques, which can be carried out by less specialized healthcare providers, might not be equivalent to endoscopy for CRC screening but seems more realistic for areas with fewer resources. Awareness has been highlighted as the most pivotal element for the effective implementation of any screening program concerning CRC. Moreover, multiple studies have demonstrated that outreach strategies and community-based educational programs are associated with encouraging outcomes, yet a centrally coordinated expansion of these programs could provide more consistent results. Additionally, patient navigator programs, wherever implemented, have increased CRC screening and improved follow-up. Therefore, global coordination and patient education seem to be the main areas on which policy making needs to focus.

Circulating Levels of T-Cell Traits and the Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

Amyotrophic lateral sclerosis (ALS) represents a rare and potentially fatal neurodegenerative disease. Diverse T-cell subsets could potentially exert diametrically opposite impacts upon ALS development. A two-sample Mendelian randomization (MR) analysis was performed to investigate the correlation between 244 T-cell subsets and ALS risk. Genetic instrumental variables were procured from a standard genome-wide association study (GWAS) that encompassed 244 T-cell subsets in 3757 individuals of European lineage. ALS-related data were collected from a GWAS comprising 20,806 ALS instances and 59,804 European control participants. Multiple sensitivity analyses were performed to verify the robustness of the significant results. Reverse MR analysis was used for delineating the effects of ALS on the characteristics of T-cells. After multiple comparison corrections, 24 out of the 244 subtypes demonstrated a potential association with ALS risk. Significantly, 75% of these associations encompassed the expression of the CD3 on diverse T-cell subtypes, revealing a highly consistent inverse relation to ALS risk. The proportion of T regulatory cells (Tregs) in CD4+ T cells and secreting Tregs in CD4+ T cells demonstrated negative associations with the risk of ALS. CCR7 expression on naive CD4+ T cells and CCR7 expression on naive CD8+ T cells showed positive associations with ALS risk. Certain T-cell subsets, particularly those identified by CD3 expression on terminally differentiated CD8+ T cells, proportions of Tregs, and CCR7 expression, indicated an association with ALS risk. These findings harmonize with and extend previous observational studies investigating the involvement of T lymphocyte subset-induced immunological processes in ALS.

Lithium Exposure and Risk of Major Neurocognitive Disorders: A Systematic Review and Meta-analysis.

Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association. A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models. Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15). The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.

Survival Outcomes in Stage IV Gastric Cancer Patients with Krukenberg Tumors: A Systematic Review and Meta Analysis.

Stage IV gastric cancer patients with Krukenberg tumors typically exhibit poor survival outcomes, often less than 2years. The management of this tumor subgroup remains non-standardized, and the impact of oophorectomy on survival remains uncertain. In this study, we systematically analyzed survival outcomes among gastric cancer patients with ovarian metastases who underwent standard chemotherapy, surgical resection of ovarian metastases, or combined chemotherapy and surgery. We conducted a systematic reviewand meta-analysis of randomized controlled trials and observational studies retrieved from MEDLINE (PubMed), Embase, and the Cochrane Library until January 25, 2024,applying the Boolean logic. Participants included individuals with pathologically and radiologically confirmed ovarian metastasis or clinically symptomatic cases with imaging evidence. Statistical analyses were performed using R (v.4.3.2., Vienna). The study was registered with PROSPERO(ID-CRD42023488373). A total of 1502 patients from 17 retrospective studies were pooled for analysis of overall survival (OS) outcomes. The OS in the standard chemotherapy cohort, as determined by the random effects model, was 6.708months (95% CI 3.867 to 9.548; P<0.0001), with non-significant heterogeneity (I2 = 5.5%). In the surgical resection cohort, OS was 12.786months (95% CI 6.9 to 18.671; P<0.0001), with low heterogeneity (I2 = 0%). In the combined chemotherapy and surgical resection cohort, OS was 16.228months (95% CI 12.254 to 20.202), with insignificant heterogeneity (I2 = 0%). This meta-analysis offerskey insights into survival outcomes associated with different therapeutic modalities in gastric cancer with Krukenberg metastases. It provides valuable evidence for clinical decision-making and future research directions. While the combined approach of chemotherapy and surgery demonstrates the highest effect size for OS, careful consideration of patient-centric approaches is essential in the oncological care landscape.

Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis.

There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.

Hadronic physics from a Wilson fermion mixed-action approach: charm quark mass and D(s)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$D_{(s)}$$\\end{document} meson decay constants

We present our first set of results for charm physics, using the mixed-action setup introduced in a companion paper [1]. Maximally twisted Wilson valence fermions are used on a sea of non-perturbatively O(a)-improved Wilson fermions, made up by CLS Nf=2+1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$N_\\mathrm {\\scriptstyle f}=2+1$$\\end{document} ensembles. Our charm-sector observables are free from O(amc)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$O(am_c)$$\\end{document} discretisation effects, without need of tuning any improvement coefficient, and show continuum-limit scaling properties consistent with leading cutoff effects of O(a2)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$O(a^2)$$\\end{document}. We consider a subset of CLS ensembles – including four values of the lattice spacing and pion masses down to 200 MeV – allowing to take the continuum limit and extrapolate to the physical pion mass. A number of techniques are incorporated in the analysis in order to estimate the systematic uncertainties of our results for the charm quark mass and the D(s)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$D_{(s)}$$\\end{document}-meson decay constants. This first study of observables in the charm sector, where the emphasis has been on the control of the methodology, demonstrates the potential of our setup to achieve high-precision results.

The association of home blood pressure with all-cause mortality in hemodialysis patients: A prospective observational study.

Prior observational studies conducted in the hemodialysis population have suggested a reverse association between dialysis-unit blood pressure (BP) and mortality. The present study aimed to investigate the prognostic association of home versus dialysis-unit BP with all-cause mortality in hemodialysis patients. At baseline, 146 patients receiving maintenance hemodialysis underwent assessment of their BP with the following methods: (i) 2-week averaged routine predialysis and postdialysis BP measurements; (ii) home BP monitoring for 1 week that included duplicate morning and evening BP measurements with the use of validated devices. Over a median follow-up period of 38 months (interquartile range [IQR]: 22-54), 44 patients (31.1%) died. In Kaplan-Meier curves, predialysis and postdialysis systolic BP (SBP) was not associated with all-cause mortality, while home SBP appeared to be of prognostic significance (log rank p = 0.029). After stratifying patients into quartiles, all-cause mortality was lowest when home SBP was ranging from 128.1 to 136.8 mmHg (quartile 2). In univariate Cox regression analysis, using quartile 2 as a referent category, the risk of all-cause mortality was 3.32-fold higher in quartile 1, 1.53-fold higher in quartile 3 and 3.25-fold higher in quartile 4. The risk-association remained unchanged after adjustment for several confounding factors (adjusted hazard ratio: 4.79, 1.79, 3.63 for quartiles 1, 3, and 4 of home systolic BP, respectively). Our findings suggest that among hemodialysis patients, 1-week averaged home SBP is independently associated with all-cause mortality. In sharp contrast, SBP recorded either before or after dialysis over 2 weeks is not prognostically informative.

Genetic Prediction of Osteoporosis by Anti-Müllerian Hormone Levels and Reproductive Factors in Women: A Mendelian Randomization Study.

Previous observational studies have suggested that anti-Müllerian hormone (AMH) and reproductive factors are linked to reduced bone mineral density (BMD) and an increased risk of osteoporosis (OP) in women. However, related studies are limited, and these traditional observational studies may be subject to residual confounders and reverse causation, while also lacking a more comprehensive observation of various reproductive factors. Univariate and multivariate two-sample Mendelian randomization analyses were conducted to determine the causal associations of AMH levels and six reproductive factors with BMD and OP, using the random-effects inverse-variance weighted method. Heterogeneity was assessed using Cochran's Q-statistic, and sensitivity analyses were performed to identify causal correlations. Age at menarche (AAM) was negatively associated with total body BMD (TB-BMD) in females aged 45-60 and over 60years, as well as with heel bone mineral density (eBMD). Conversely, age at natural menopause (ANM) was positively associated with TB-BMD in the same age ranges and with eBMD. ANM was only causally associated with self-reported OP and showed no significant correlation with definitively diagnosed OP. Neither AMH level nor other reproductive factors were significantly associated with a genetic predisposition to BMD at any age and OP. Later AAM and earlier ANM are significantly genetically causally associated with decreased BMD but not with OP. AMH levels, length of menstrual cycle, age at first birth, age at last birth, and number of live births, in terms of genetic backgrounds, are not causally related to BMD or OP.

Molnupiravir Use Among Patients with COVID-19 in Real-World Settings: A Systematic Literature Review.

Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective was to conduct a systematic literature review (SLR) of evidence on the effectiveness of MOV in reducing the risk of severe COVID-19 outcomes in real-world outpatient settings. The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and using pre-determined population, intervention, comparison, outcome, time, and study design inclusion criteria. Eligible studies were published between January 1, 2021, and March 10, 2023, and evaluated the real-world effectiveness of MOV compared to no treatment in reducing the risk of severe COVID-19 outcomes among outpatients ≥ 18years of age with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Nine studies from five countries were included in the review. The size of the MOV-treated group ranged from 359 to 7818 individuals. Omicron variants of SARS-CoV-2 were dominant in all study periods. Most studies noted differences in the baseline characteristics of the MOV-treated and untreated control groups, with the treated groups generally being older and with more comorbidities. Eight studies reported that treatment with MOV was associated with a significantly reduced risk of at least one severe COVID-19 outcome in at least one age group, with greater benefits consistently observed among older age groups. In this SLR study, treatment with MOV was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the MOV-treated and control groups may have led to underestimation of the effectiveness of MOV in many observational studies. Real-world studies published to date thus provide additional evidence supporting the continued benefits of MOV in non-hospitalized adults with COVID-19.

Can narrow-diameter implants enhance patient-reported outcomes for mandibular implant-retained overdentures?

A systematic review and meta-analysis. To evaluate and compare stability and functionality between narrow and standard implant-retained mandibular overdentures in edentulous patients from multiple perspectives. Assessments included clinical parameters [survival rate (SR) and marginal bone loss (MBL)], along with patient-reported outcome measures (PROMs) including patient satisfaction and oral health-related quality of life (OHRQoL). The study protocol followed PRISMA criteria for reporting reviews and meta-analyses. Using appropriate keywords, electronic search was conducted in each of the following databases: Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus, up to July 22, 2022. There were no restrictions based on language, publication type, or publication date. Additionally, ongoing studies were explored in ClinicalTrials.gov and WHO ICTRP, while cross-references in each selected study were manually examined. The eligible studies were randomized controlled trials (RCTs) or controlled clinical trials (CCTs) comparing narrow implants (diameter ≤ 3.5 mm) to standard implants (diameter > 3.5-4.5 mm) retaining mandibular overdentures in edentulous patients. Excluded were studies with unclear implant diameter information, fewer than 5 patients per group, observational studies, reviews, and laboratory studies. Two authors independently conducted study selection, data collection, and analysis, resolving any discrepancies through discussion with a third author. Methodological quality was assessed using RoB-2 and ROBINS-I tools. Implant SR and MBL measurements at final follow-up were recorded, while patient satisfaction and OHRQoL were evaluated using visual analogue scale (VAS-100) and oral health impact profile (OHIP) questionnaire, respectively. After duplicate removal, 782 publications and 83 registered clinical trials were identified, of which 26 were eligible for full-text assessment. Ultimately, the quantitative evaluation included 12 publications from 8 independent studies: 4 parallel design RCTs and 4 CCTs. Risk of bias assessment revealed variations among the studies, with only one study being rated as having low risk. The follow-up periods ranged from 1 to 3 years. Meta-analysis showed no significant difference in SR and MBL between narrow and standard implant groups (p = 0.29 and p = 0.93, respectively), with considerable heterogeneity (I2 = 100% and I2 = 78%, respectively). Regarding PROMs, the narrow implant group showed significantly higher levels of patient satisfaction (mean difference (MD): 8.18; 95% CI: 5.83 to 10.53; p < 0.00001; I2 = 36%) and exhibited a significant improvement in OHRQoL (MD: -4.36; 95% CI: -6.83 to -1.89; p < 0.001; I2 = 55%) compared to the standard implant group. For implant-retained mandibular overdentures, the use of narrow implants is associated with comparable SR and MBL, along with higher patient satisfaction and better OHRQoL improvement as compared to standard implants, offering a viable alternative option for patients with diminished alveolar bone width.

25years of lipid-lowering therapy: secular trends in therapy of coronary patients.

Guidelines on dyslipidemia and lipid-lowering therapy (LLT) over the years recommend lower low-density lipoprotein cholesterol (LDL-C) goals by more intense therapy. Nevertheless, LDL‑C has increased in the general population. Real-world trends of LLT medication as well as of LDL‑C levels in cardiovascular high-risk patients are unclear. From 2158 patients who were referred for elective coronary angiography, lipid medication was analyzed at admission in three cardiovascular observational studies (OS) over the last 25years: OS1: 1999-2000, OS2: 2005-2008 and OS3: 2022-2023. The three studies were performed at the same cardiology unit of atertiary care hospital in Austria. The proportion of patients without LLT significantly decreased from OS1 through OS2 to OS3 (49.4%, 45.6%, and 18.5%, respectively, ptrend < 0.001). Moreover, the percentage of patients under high-intensity statin treatment significantly increased from 0% to 5.1%, and 56.5% (ptrend < 0.001). Significantly more patients became treated by more than one compound (OS1: 1.8%, OS2: 1.6%, OS3: 31.2%; ptrend < 0.001). In the latest OS3, atrend to fixed-dose combination of statins with ezetimibe was observed. Mean LDL‑C levels decreased from 129 mg/dL over 127 mg/dL to 83 mg/dL, respectively (ptrend < 0.001). Of the patients on high-intensity therapy 34% met the recent ESC/EAS goals (LDL-C < 55 mg/dL), but only 3% on non-intense therapy. We conclude that during the observational period of aquarter of acentury, treatment intensity increased and LDL‑C levels improved considerably. Guidelines apparently matter in this high-risk population and are considered by primary care physicians.

Use of digital media by adolescents for sexual and reproductive health and rights communication in sub-Saharan Africa: a protocol for systematic review

BackgroundWithin the sub-Saharan African region, there is a growing concern for sexual and reproductive health and rights communication, and more particularly, for adolescents. Given the existing barriers associated with face-to-face access, the need to use digital media to access information and services has become desirable and imperative, especially so due to the COVID-19 pandemic. However, in sub-Saharan Africa, a synthesis of evidence that informs adolescents’ digital media engagements for sexual and reproductive health and rights (SRHR) communication is limited. This systematic review therefore aims to examine and synthesize evidence on use of digital media for sexual and reproductive health and rights communication by adolescents in sub-Saharan Africa.MethodsA search for peer-reviewed articles will be conducted in PubMed, ScienceDirect, Scopus, Embase, Web of Science, PsychINFO and Google Scholar with emphasis on those published between 2000 and 2023. Only observational and qualitative studies will be included. Quality assessment of included articles will be done using standardized checklists from the Joanna Briggs Institute. Both descriptive and narrative summaries will be used to appraise evidence from included studies.DiscussionThis review will be essential in providing information on the types of digital media adolescents use, the various SRHR issues they use this platform to address and their reasons for using it and associated challenges. It will also contribute to the advocacy for the inclusion of these technologies in the teaching and learning, provision of and access to SRHR information and services by teachers, public health providers and peer educators in the subregion.Systematic review registrationPROSPERO CRD42020211491. This protocol follows the PRISMA-P guidelines for reporting systematic reviews.

Early source control of infection in patients seen in the emergency department: a systematic review

The term source (or focus) control encompasses all those physical measures that can be used to reduce the inoculum and modify those factors in the infectious medium that promote microbial growth or foreign antimicrobial defenses of the host. The main objective of this systematic review (SR) is to know and compare whether early detection and control of the focus (in less than 6 hours) in adult patients treated in the ED for severe infection or sepsis, compared to not controlling the focus or delayed focus control (more than 12 hours) is more effective and safer (improves clinical evolution, mortality, complications, hospital stay or need for ICU admission). A systematic review is carried out following the PRISMA regulations in the databases of PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase and ClinicalTrials.gov from January 2000 to December 31, 2023 without language restrictions and using a combination of MESH terms: "Source Control", "Early" "Infection OR Bacterial Infection OR Sepsis", "Emergencies OR Emergency OR Emergency Department" and "Adults". Observational cohort studies were included. No meta-analysis techniques were performed, but results were compared narratively. A total of 1,658 articles were identified, of which 2 that met the inclusion criteria and were classified as high quality were finally analyzed. The included studies represent a total of 2,404 patients with 678 cases in which an intervention was performed to control the focus (28.20%). In the first study, 28-day mortality was lower in patients who underwent an intervention to control the focus (12.3% vs. 22.5%; P <0.001), with an adjusted HR of 0.538 (95% CI: 0.389-0.744; P<0.001). In the second, it was demonstrated that the time elapsed from when the patient was evaluated for the first time and was hemodynamically stabilized, until the start of surgery was associated with his survival at 60 days with an OR of 0.31 (95% CI: 0.19-0.45; P <0.0001). In fact, for each hour of delay an adjusted OR of 0.29 (95% CI: 0.16-0.47; P<0.0001) is established. So if the intervention is performed before 2 hours at 60 days, 98% of the patients are still alive, if it is performed between 2-4 hours it is reduced to 78%, if it is between 4-6 hours it drops to 55%, but if it is done for more than 6 hours there will be no survivors at 60 days. This review shows that source control carried out after the evaluation of patients attending the ED reduces short-term mortality (30-60 days) and that it would be advisable to implement any required source control intervention as soon as possible, ideally early (within 6 hours).

A scoping review evaluating physical and cognitive functional outcomes in cancer survivors treated with chemotherapy: charting progress since the 2018 NCI think tank on cancer and aging phenotypes.

The primary goal of this scoping review was to summarize the literature published after the 2018 National Cancer Institute think tank, "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors," on physical and cognitive functional outcomes among cancer survivors treated with chemotherapy. We focused on the influence of chemotherapy on aging-related outcomes (i.e., physical functional outcomes, cognitive functional outcomes, and frailty), given the known associations between chemotherapy and biologic mechanisms that affect aging-related physiologic processes. A search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, for manuscripts published between August 2018 and July 2023. Eligible studies: 1) included physical function, cognitive function, and/or frailty as outcomes; 2) included cancer survivors (as either the whole sample or a subgroup); 3) reported on physical or cognitive functional outcomes and/or frailty related to chemotherapy treatment (as either the whole sample or a subgroup); and 4) were observational in study design. The search yielded 989 potentially relevant articles, of which 65 met the eligibility criteria. Of the 65 studies, 49 were longitudinal, and 16 were cross-sectional; 30 studies (46%) focused on breast cancer, 20 studies (31%) focused on the age group 60 + years, and 17 (26%) focused on childhood cancer survivors. With regards to outcomes, 82% of 23 studies reporting on physical function showed reduced physical function, 74% of 39 studies reporting on cognitive functional outcomes found reduced cognitive function, and 80% of 15 studies reporting on frailty found increasing frailty among cancer survivors treated with chemotherapy over time and/or compared to individuals not treated with chemotherapy. Fourteen studies (22%) evaluated biologic mechanisms and their relationship to aging-related outcomes. Inflammation was consistently associated with worsening physical and cognitive functional outcomes and epigenetic age increases. Further, DNA damage was consistently associated with worse aging-related outcomes. Chemotherapy is associated with reduced physical function, reduced cognitive function, and an increase in frailty in cancer survivors; these associations were demonstrated in longitudinal and cross-sectional studies. Inflammation and epigenetic age acceleration are associated with worse physical and cognitive function; prospective observational studies with multiple time points are needed to confirm these findings. This scoping review highlights the need for interventions to prevent declines in physical and cognitive function in cancer survivors who have received chemotherapy.

Accuracy of methods to estimate central aortic SBP via upper arm cuff: a systematic review and meta-analysis.

Central aortic BP may predict cardiovascular outcomes better than upper arm brachial BP. In recent years, technology has enabled central BP estimation by recording a peripheral BP waveform from a standard upper arm cuff. The accuracy of these devices is not well documented, and this study aimed to address this issue. This study was a systematic review, conducted according to PRISMA guidelines, of observational studies published between 2008 and 2023 that reported accuracy testing of cuff-based central BP devices, compared with reference invasive aortic BP. The primary analysis was stratified according to each commercially available device. Pooled estimates were calculated using random-effects models based on mean differences and standard errors. Six thousand four hundred and fifteen studies were screened, and 27 studies met inclusion criteria (plus one unpublished study). This generated data for seven devices that are commercially available, which were tested among 2125 adult participants. There was very high heterogeneity when all devices were pooled (I2 = 97.5%), and, when stratified by device, the accuracy of estimated central BP was highly device-dependent (range of accuracy across different devices -12.4 mmHg (-16.3 to -8.5) to 3.2 mmHg (0.2-6.1). Two of the seven commercially available devices had not undergone external validation testing. The accuracy of commercially available cuff-based central BP devices is highly device-specific and not all are accurate for the estimation of central SBP. These findings have major implications for the appropriate interpretation of studies that use cuff-based estimated central BP.

Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime.

Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents. To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage. In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023. The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection. Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days. Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.

Role of Vena Cava Filter in the Prophylaxis and Treatment of Venous Thromboembolism in Injured Adult Patients: A Systematic Review, Meta-Analysis, and Practice Management Guideline from the Eastern Association for the Surgery of Trauma [RETRACTED

Injured patients are at an increased risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). Inferior vena cava (IVC) filters have been used in injured patients to prevent venous thromboembolism (VTE), but current evidence-based guidelines are lacking. Questions regarding IVC filter use in injured patients with clearly defined Population(s), Intervention(s), Comparison(s), and appropriately selected Outcomes (PICO) were formulated. The study sought to understand the evidence behind use of ultra short term IVC filters and use of IVC filters in injured patients with and without known VTE who are unable to receive therapeutic anticoagulation and chemoprophylaxis, respectively. A literature search and review was conducted, followed by meta-analysis. The quality of evidence was assessed per Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. There were twenty-one studies that were analyzed. Three studies were randomized controlled trials (RCTs), three were observational studies, and fifteen studies were retrospective studies. In injured patients without known acute VTE who cannot receive chemoprophylaxis, we recommend against placement of an IVC filter due to associated higher rate of mortality, DVT, PE, and length of stay. The quality of evidence was assessed to be low. In injured patients with known DVT who cannot receive chemoprophylaxis we conditionally recommend against placement of an IVC filter. The quality of evidence was assessed to be very low. No recommendations can be made with respect to placement of ultra short term IVC filters based upon available data. IVC filters should not be placed routinely for prophylaxis in injured adult patients without known VTE who cannot receive chemoprophylaxis. The taskforce conditionally recommends against the placement of IVC filter in injured adult patients with known DVT who cannot receive chemoprophylaxis. Guideline; Systematic review/meta-analysis, level IV.

Ethical Problems of Observational Studies and Big Data Compared to Randomized Trials.

The temptation to use prospective observational studies (POS) instead of conducting difficult trials (RCTs) has always existed, but with the advent of powerful computers and large databases, it can become almost irresistible. We examine the potential consequences, were this to occur, by comparing two hypothetical studies of a new treatment: one RCT, and one POS. The POS inevitably submits more patients to inferior research methodology. In RCTs, patients are clearly informed of the research context, and 1:1 randomized allocation between experimental and validated treatment balances risks for each patient. In POS, for each patient, the risks of receiving inferior treatment are impossible to estimate. The research context and the uncertainty are down-played, and patients and clinicians are at risk of becoming passive research subjects in studies performed from an outsider's view, which potentially has extraneous objectives, and is conducted without their explicit, autonomous, and voluntary involvement and consent.