Epidemiological Study in Antiviral Innate Immunity.

This chapter summarizes the epidemiological study design of natural immune epidemiology studies based on recent COVID-19-related research. The epidemiological studies on antiviral innate immunity have mainly included randomized controlled trials (RCTs) and observational studies. Importantly, this chapter will discuss how to use these methodologies to answer an epidemiological question of natural immunity in the viral infection process based on previous studies. An observational case- or cohort-based study of antiviral innate immunity may support this theoretical hypothesis but is not appropriate for clinical practice or treatment. RCTs are the gold standard for epidemiological studies and occupy a greater role in the hierarchy of evidence.

Double burden of gestational diabetes and pregnancy-induced hypertension in Ethiopia: A systematic review and meta-analysis of observational studies.

BACKGROUND: The coexistence of gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) amplifies the risk of maternal and perinatal mortality and complications, leading to more severe adverse pregnancy outcomes. This systematic review and meta-analysis aimed to assess the double burden of GDM and PIH (GDM/PIH) among pregnant women in Ethiopia. METHODS: A comprehensive systematic search was conducted in the databases of PubMed, Cochrane Library, Science Direct, Embase, and Google Scholar, covering studies published up to May 14, 2023. The analysis was carried out using JBI SUMARI and STATA version 17. Subgroup analyses were computed to demonstrate heterogeneity. A sensitivity analysis was performed to examine the impact of a single study on the overall estimate. Publication bias was assessed through inspection of the funnel plot and statistically using Egger's regression test. RESULT: Of 168 retrieved studies, 15 with a total of 6391 participants were deemed eligible. The pooled prevalence of GDM/PIH co-occurrence among pregnant women in Ethiopia was 3.76% (95% CI; 3.29-4.24). No publication bias was reported, and sensitivity analysis suggested that excluded studies did not significantly alter the pooled prevalence of GDM/PIH co-occurrence. A statistically significant association between GDM and PIH was observed, with pregnant women with GDM being three times more likely to develop PIH compared to those without GDM (OR = 3.44; 95% CI; 2.15-5.53). CONCLUSION: This systematic review and meta-analysis revealed a high dual burden of GDM and PIH among pregnant women in Ethiopia, with a significant association between the two morbidities. These findings emphasize the critical need for comprehensive antenatal care programs in Ethiopia to adequately address and monitor both GDM and PIH for improved maternal and perinatal health outcomes.

ABO blood types and head and neck cancer: a systematic review with meta-analysis of observational studies.

OBJECTIVES: This research aims to explore the correlation between ABO blood groups and neoplasms in the head and neck region, specifically investigating the susceptibility of different blood groups to tumours. DESIGN: Systematic review and meta-analysis. DATA SOURCES: CNKI, WANFANG DATA, PubMed, Web of Science and Embase databases were systematically searched from inception to January 2024. ELIGIBILITY CRITERIA: All studies of ABO blood type and head and neck tumours will be included in this study. DATA EXTRACTION AND SYNTHESIS: A systematic literature review was performed using digital platforms on CNKI, WANFANG DATA, PubMed, Web of Science and Embase databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for meta-analysis. Two authors independently extracted the data and assessed the quality of included studies. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Comparisons were made between blood types A, B, AB and their combined group versus O, along with subgroup analyses. Systematic analysis was performed by using Review Manager V.5.4 and Stata V.18 statistical software. RESULTS: 30 articles were included, involving 737 506 subjects, among which 21 382 were patients with head and neck tumours. The overall analysis indicated a significant association between type AB blood (OR 0.762, 95% CI 0.637 to 0.910) and a reduced risk of head and neck tumours. In the Caucasoid race, type A blood is significantly linked to an elevated likelihood of head and neck tumours (OR 1.353, 95% CI 1.076 to 1.702), while in the Mongoloid race, type AB blood is significantly linked to a reduced likelihood of developing tumours in the head and neck area (OR= 0.732, 95% CI 0.588 to 0.910). No significant associations were found in the subgroup analysis by gender. Regarding different types of cancer, type A blood is significantly associated with an increased risk of salivary gland tumours (OR 1.338, 95% CI 1.075 to 1.665), and type AB blood is significantly linked to a lower likelihood of nasopharyngeal carcinoma (OR 0.590, 95% CI 0.429 to 0.812). CONCLUSION: A correlation exists between ABO blood groups and tumours in the head and neck region. However, the link between blood type and head and neck tumours requires further confirmation through more prospective studies. PROSPERO REGISTRATION NUMBER: CRD42024510176.

Survival, morbidity, and quality of life in pulmonary arterial hypertension patients: a systematic review of outcomes reported by population-based observational studies.

BACKGROUND: Comprehensive summaries on real-world outcomes in pulmonary arterial hypertension (PAH)-a rare, incurable condition, are lacking. We conducted a systematic literature review to describe current survival, morbidity, and quality of life (QoL) outcomes in adult and pediatric PAH patients. We searched Medline and Embase electronic databases, clinicaltrials.gov, and encepp.eu entries, and grey literature to identify outcome estimates for right-heart catheterization-confirmed PAH patients from population-based observational studies (search date: 25 Nov 2021). Data were synthesized using a narrative approach and post-hoc subgroup meta-analyses were conducted to explore adult survival by region, disease severity, representativeness, and study period. The search yielded 7473 records. Following screening and full text review, 22 unique studies with 31 individual reports of outcomes were included. Studies were mostly national registries (n = 21), European (n = 13) and covering adults (n = 17); only six had systematic countrywide coverage of centers. Survival was the most frequently reported outcome (n = 22). Global adult 1-, 3-, and 5-year survival ranged from 85 to 99% (n = 15), 65 to 95% (n = 14), and 50 to 86% (n = 9), respectively. Subgroup meta-analysis showed that 1-, 3-, and 5-year survival in Europe was 90% (95% CI 86-94%; n = 8), 78% (95% CI 68-86%; n = 8), and 61% (95% CI 49-72%; n = 6), respectively; 1-year survival in North America was 88% (95% CI 83-93%; n = 3) and 3-year survival in Asia was 85% (95% CI 82-88%; n = 3). No difference in survival between regions was observed. Subgroup analysis suggested higher survival in patients with better baseline functional class; however, interpretation should be cautioned due to large subgroup heterogeneity and potential missingness of data. SHORT CONCLUSION: This review describes current disease outcomes based on well-defined and representative PAH populations. There is an overall lack of follow-up data for morbidity and QoL outcomes; survival estimates for pediatric patients are scarce and may not be generalizable to the current treatment era, although publications from large pediatric registries became available after our search date. This study demonstrated a remaining unmet need world-wide to improve long-term prognosis in PAH in the current era.

Adverse pregnancy outcomes and multiple cancers risk in both mother and offspring: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. METHODS: PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). RESULTS: The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02-1.12), prostate cancer (OR = 1.02, 95% CI = 1.00-1.05), leukemia (OR = 1.18, 95% CI = 1.13-1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12-1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16-6.71); and a linear dose-response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09-1.24), respectively. CONCLUSIONS: Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.

Safety and efficacy of CyTisine for smoking cessation in a hOSPital context (CITOSP): study protocol for a prospective observational study.

Tobacco addiction is the primary preventable factor contributing to global mortality, and nicotine is one of the substances with the greatest potential for addiction. With a strong affinity for the α4ß2 subtype receptor, cytisine (CYT) functions as a partial agonist of the acetylcholine nicotinic cholinergic receptor. It counteracts the effects of nicotine without causing any withdrawal symptoms. These features, combined with its limited mild adverse effects and minimal drug-drug interactions, make cytisine a cost-effective treatment for smoking cessation. The current protocol describes a prospective observational study on the safety and efficacy of CYT administered to inpatient smokers of the Integrated University Hospital of Verona (IUHVR), Veneto (Italy). This is a monocentric, observational, and prospective study on both sex smokers over the age of 18 years admitted to the IUHVR who meet the criteria for recruitment and have given their consent. Eligible participants will be assigned to the CYT intervention based on the West dosing schedule and will be followed up for 12 months from treatment initiation. Evaluation of safety, efficacy, and compliance will be assessed at 7 and 25 days, with follow-up at 3, 6, and 12 months from the start of the treatment (quit day). During each visit, any adverse events or adverse reactions reported by patients following the intake of CYT will be evaluated. This study will contribute, for the first time, to the knowledge about the use of CYT for smoking cessation in a hospital setting.

Ultra-processed Food Intake During Pregnancy and its Impact on Maternal Diet Quality and Weight Change: A Systematic Review of Observational Studies.

PURPOSE OF REVIEW: Adequate and balanced nutrition during pregnancy is essential for both the mother's and fetus's health. The increased dietary intake of ultra-processed foods (UPFs) and their significant share in the diet negatively affects diet quality and gestational weight gain during pregnancy. The aim of this systematic review was to examine the association of UPFs consumption with diet quality and gestational weight change among healthy pregnant women, using data from observational studies (PROSPERO Identifier: CRD42023468269) from the last 10 years. RECENT FINDINGS: A search was performed in Pubmed, Wiley, Scopus, and Web of Science, and studies published in english language were selected. Study selection and data extraction were made by determining the exclusion and eligible inclusion criterias according to the PECOS framework. Of the 12 studies included, 5 were longitudinal cohort studies and 7 were cross-sectional studies. On average, half of the energy in the participants' daily diets came from UPFs in 3 studies, but the energy share of UPFs was about 20-30% in the remainder studies. UPFs-enriched maternal diet was associated with less dietary intake of legumes, vegetables, fruits and protein sources (seafood and plant protein, total protein) and greater consumption of refined grains compared to those who consume less UPFs. In parallel, UPFs consumption was negatively associated with Healthy Eating Index. UPF intake during pregnancy has a negative impact on diet quality and gestational weight gain. Increasing awareness of UPFs during this period may reduce potential complications during pregnancy and fetal growth.

Objectively measured daily steps and health outcomes: an umbrella review of the systematic review and meta-analysis of observational studies.

OBJECTIVES: The purpose of this review is to summarise the evidence from a systematic review and meta-analysis of observational studies that objectively measure daily steps and health outcomes. DESIGN: This is an umbrella review. DATA SOURCES: PubMed, Embase, Scopus, the Cochrane Library and Web of Science databases were searched through 31 January 2024. ELIGIBILITY: We included systematic reviews of observational studies (with or without meta-analysis) that assessed the association of objectively measured daily steps with human health-related outcomes. Methodological quality was assessed using 'A MeaSurement Tool to Assess systematic Reviews 2'. RESULTS: A total of 10 systematic reviews and 6 health outcomes were included after excluding irrelevant and duplicate studies. Higher daily steps were associated with more benefits than harms for a range of health-related outcomes, including all-cause mortality, cardiovascular event, skeletal muscle lesions, metabolic diseases and respiratory disease. A dose-response analysis showed that an increase of 500-1000 steps per day was associated with lower all-cause mortality and cardiovascular events. Beneficial associations were also found in patients with asthma and acutely hospitalised older adults. Conversely, one study within a systematic review suggested that higher daily steps (≥10 000) might be associated with an increased 52% risk of meniscal pathologies in individuals without knee osteoarthritis. However, one study within a systematic review suggested a potential increased risk of meniscal pathologies in individuals without knee osteoarthritis. Specifically, those exceeding 10 000 steps per day showed a 52% increase in risk. CONCLUSION: The results of this study suggest that daily steps are associated with a lower risk of all-cause mortality and cardiovascular events. Future research could focus on identifying specific populations that may benefit most from increased daily steps and exploring potential mechanisms to enhance our understanding of how daily steps contribute to improved health outcomes. PROSPERO REGISTRATION NUMBER: CRD42022347055.

Correlation of the treatment sensitivity of patient-derived organoids with treatment outcomes in patients with head and neck cancer (SOTO): protocol for a prospective observational study.

INTRODUCTION: Organoids have been successfully used in several areas of cancer research and large living biobanks of patient-derived organoids (PDOs) have been developed from various malignancies. The characteristics of the original tumour tissue such as mutation signatures, phenotype and genetic diversity are well preserved in organoids, thus showing promising results for the use of this model in translational research. In this study, we aim to assess whether we can generate PDOs from head and neck squamous cell carcinoma (HNSCC) samples and whether PDOs can be used to predict treatment sensitivity in HNSCC patients as well as to explore potential biomarkers. METHODS AND ANALYSIS: This is a prospective observational study at a single centre (Guy's and St Thomas' NHS Foundation Trust) to generate PDOs from patients' samples to assess treatment response and to correlate with patients' treatment outcomes. Patients will be included if they are diagnosed with HNSCC undergoing curative treatment (primary surgery or radiotherapy) or presenting with recurrent or metastatic cancers and they will be categorised into three groups (cohort 1: primary surgery, cohort 2: primary radiotherapy and cohort 3: recurrent/metastatic disease). Research tumour samples will be collected and processed into PDOs and chemosensitivity/radiosensitivity will be assessed using established methods. Moreover, blood and other biological samples (eg, saliva) will be collected at different time intervals during treatment and will be processed in the laboratory for plasma and peripheral blood mononuclear cell (PBMC) isolation. Plasma and saliva will be used for circulating tumour DNA analysis and PBMC will be stored for assessment of the peripheral immune characteristics of the patients as well as to perform co-culture experiments with PDOs. SOTO study (correlation of the treatment Sensitivity of patient-derived Organoids with Treatment Outcomes in patients with head and neck cancer) uses the collaboration of several specialties in head and neck cancer and has the potential to explore multiple areas of research with the aim of offering a valid and effective approach to personalised medicine for cancer patients. ETHICS AND DISSEMINATION: This study was approved by North West-Greater Manchester South Research Ethics Committee (REC Ref: 22/NW/0023) on 21 March 2022. An informed consent will be obtained from all participants prior to inclusion in the study. Results will be disseminated via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT05400239.

Disease-Modifying Antirheumatic Drugs and Dementia Prevention: A Systematic Review of Observational Evidence in Rheumatoid Arthritis.

BACKGROUND: Many observational studies have examined the association of disease-modifying antirheumatic drugs (DMARDs) with dementia risk, but the evidence has been mixed, possibly due to methodological reasons. This systematic review (PROSPERO: CRD42023432122) aims to assess existing observational evidence and to suggest if repurposing DMARDs for dementia prevention merits further investigation. METHODS: Four electronic databases up to October 26, 2023, were searched. Cohort or case-control studies that examined dementia risk associated with DMARDs in people with rheumatoid arthritis were included. Risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) criteria. Findings were summarized by individual drug classes and by risk of bias. RESULTS: Of 12,180 unique records, 14 studies (4 case-control studies, 10 cohort studies) were included. According to the ROBINS-I criteria, there were 2 studies with low risk of bias, 1 study with moderate risk, and 11 studies with serious or critical risk. Among studies with low risk of bias, one study suggested that hydroxychloroquine versus methotrexate was associated with lower incident dementia, and the other study showed no associations of tumor necrosis factor (TNF) inhibitors, tocilizumab, and tofacitinib, compared to abatacept, with incident dementia. CONCLUSION: Studies that adequately addressed important biases were limited. Studies with low risk of bias did not support repurposing TNF inhibitors, tocilizumab, abatacept or tofacitinib for dementia prevention, but hydroxychloroquine may be a potential candidate. Further studies that carefully mitigate important sources of biases are warranted, and long-term evidence will be preferred.

Prospective observational non-randomized trial protocol for surgical planner 3D image processing & reconstruction for locally advanced colon cancer.

INTRODUCTION: Colon cancer presents significant surgical challenges that necessitate the development of precise strategies. Standardization with complete mesocolic excision (CME) is common, but some cases require extended resections. This study investigates the use of 3D Image Processing and Reconstruction (3D-IPR) to improve diagnostic accuracy in locally advanced colon cancer (LACC) with suspected infiltration and achieve R0 surgery. METHODS: Single-center, prospective, observational, comparative, non-randomized study. •Participants: Patients aged > 18 years undergoing LACC surgery, as indicated by CT scans, confirmed via colonoscopy. Exclusion criteria include neoadjuvant therapy, suspected carcinomatosis on CT, and unresectable tumors. •Interventions: 3D-IPR models are used for surgical planning, providing detailed tumor and surrounding structure metrics. Surgical procedures are guided by CT scans and intraoperative findings, categorized by surgical margins as R0, R1, or R2. •Objective: The primary goal is to evaluate 3D-IPR's utility in achieving R0 resection in LACC with suspected infiltration. Secondary objectives include assessing preoperative surgical strategy, comparing CT reports, detecting adenopathy, and identifying vascularization and anatomical variants. • Outcome: The main outcome is the diagnostic accuracy of 3D-IPR in determining tumor infiltration of neighboring structures compared to conventional CT scans, using definitive pathological reports as the gold standard. RESULTS: •Recruitment and Number Analyzed: The study aims to recruit about 20 patients annually over two years, focusing on preoperative 3D-IPR analysis and subsequent surgical procedures. •Outcome Parameters: These include loco-regional and distant recurrence rates, peritoneal carcinomatosis, disease-free and overall survival, and mortality due to oncologic progression. •Harms: No additional risks from CT scans, as they are mandatory for staging colon tumors. 3D-IPR is derived from these CT scans. DISCUSSION: If successful, this study could provide an objective tool for precise tumor extension delimitation, aiding decision-making for radiologists, surgeons, and multidisciplinary teams. Enhanced staging through 3D-IPR may influence therapeutic strategies, reduce postsurgical complications, and improve the quality of life of patients with LACC. TRIAL REGISTRATION: Trial is registered at ISRCTN registry as ISRCTN81005215. Protocol version I (Date 29/06/2023).

The Impact of Hormone Replacement Therapy on the Risk of Heart Failure in Postmenopausal Women: A Meta-Analysis of Clinical and Observational Studies.

PURPOSE: The relationship between heart failure (HF) and hormone replacement therapy (HRT) in postmenopausal women remains unclear. This paper aimed to elucidate the association between HRT and HF outcomes in postmenopausal women by scrutinizing evidence from clinical trials and observational studies. METHODS: The meta-analysis was systematically executed following the PRISMA guidelines to include studies identified from the electronic databases, including PubMed, EMBASE, EBSCO, ICTRP, and NIH clinical trials. The primary endpoint of the effect comprised risk ratios (RR) for HF incidence and mortality, attended by 95% confidence intervals (CIs). The risk of bias was assessed employing the Cochrane Risk of Bias 2 (RoB2) tool for clinical trials and the Newcastle-Ottawa Scale (NOS) for observational studies. RESULTS: The search yielded a total of eight reports, originating from six individual studies, for inclusion in the current study, and 25 047 participants were included. The meta-analysis demonstrated no remarkable association between HRT and the incidence of HF in postmenopausal women (RR: 1.07, 95% CI: 0.91-1.25, p = 0.37). However, a significant reduction in all-cause mortality was observed among post-menopausal HF patients who received HRT (RR: 0.65, 95% CI: 0.49-0.87, p = 0.003). In age-related subgroup analyses, no significant change in the risk of HF was noticed among participants on HRT. CONCLUSIONS: The findings of this paper demonstrate that HRT use is not associated with a significant increase in the risk of incident HF. This meta-analysis also suggests a benefit in all-cause mortality when HRT is administered to postmenopausal women with HF.

Do authors of systematic reviews of epidemiological observational studies assess the methodologies of the included primary studies? An empirical examination of methodological tool use in the literature.

BACKGROUND: The procedures used to assess the methodological quality and risk of bias (RoB) of systematic reviews of observational dental studies have not been investigated. The purpose of this research was to examine the way that authors of systematic reviews of epidemiological observational studies published in dentistry conducted the methodological assessment of those primary studies. In the present article, we aimed to assess the characteristics and the level of reporting of tools used to assess the methodologies of these reviews. METHODS: We searched Scopus and the Web of Science from their inceptions to June 2023 for systematic reviews with meta-analyses of observational studies published in dentistry. Document selection and data extraction were performed in duplicate and independently by two authors. In a random sample of 10% of the systematic reviews, there was an agreement of more than 80% between the reviewers; data selection and extraction were conducted in the remaining 90% of the sample by one author. Data on the article and systematic review characteristics were extracted and recorded for descriptive reporting. RESULTS: The search in the two databases resulted in the inclusion of 3,214 potential documents. After the elimination of duplicates and the application of the eligibility criteria, a total of 399 systematic reviews were identified and included. A total of 368 systematic reviews reported a methodological tool, of which 102 used the Newcastle-Ottawa scale. Additionally, 76 systematic reviews stated the use of a modified methodological tool. Information about the approach of assessing the methodological quality or RoB of primary studies but reporting no tool or tool name occurred in 25 reviews. CONCLUSIONS: The majority of authors of systematic reviews of epidemiological observational studies published in dentistry reported the tools used to assess the methodological quality or RoB of the included primary studies. Modifying existing tools to meet the individual characteristics of various studies should be considered.

Prevalence and clinical patterns of urolithiasis in sub-saharan Africa: a systematic review and meta-analysis of observational studies.

BACKGROUND AND OBJECTIVE: Urolithiasis, the presence of stones in the urinary tract, has been linked to various clinical features and reported as a worldwide health concern. Its prevalence varies across different regions as well as populations. Several primary studies have been conducted in Sub-Saharan Africa on the situation. However, their reports are inconsistent. Hence, this review aimed to assess the pooled magnitude of urolithiasis and its clinical patterns among hospital-visiting patients in sub-Saharan Africa. METHODS: Online databases such as PubMed, Hinari, the African Journals online database, and Google Scholar were used to comprehensively search articles published until June 28, 2023, about the prevalence and clinical patterns of urolithiasis in Sub-Saharan Africa. All the included studies were conducted at hospital setting. The retrieved data was exported to STATA version 16 for final analysis. A random-effect meta-analysis model was computed to estimate the pooled results. The heterogeneity of the studies was assessed using I2 and Cochran's Q. Publication bias was examined by observation using funnel plots and statistically by Egger's tests. Subgroup analysis was performed based on the country where the studies have been conducted. RESULT: A total of 26 articles (11 reported both prevalence and clinical pattern, 5 reported only prevalence, and 10 reported only clinical patterns of urolithiasis) were included in the final systematic review and meta-analysis. The pooled prevalence of urolithiasis among hospital-visiting patients was 9.4% (95% CL = 4.9-14%), with significant heterogeneity. Most of the urolithiasis was located in the kidney, with an estimated pooled proportion of 4.6% (95% CI = 2.7, 6.5), followed by bladder stone-2.0% (95% CI = 0.7, 3.4), ureteral stone-1.8% (95% CI = 0.7, 2.9), and urethral stone-0.2% (95% CI = 0.00, 0.05). The subgroup analysis showed the highest prevalence of urolithiasis was found in Mauritian, 28.1% (95%CI 24.5, 31.7), followed by Ethiopia 18.1%, and the lowest was in Eritrea, 1.0%. A sensitivity analysis using the random-effects model found no influential study on the pooled prevalence of urolithiasis. Evidence of significant publication bias was observed and trim-fill analysis was conducted for adjustment. Accordingly, two missing studies were identified, and after adjustment, the combined prevalence of urolithiasis was estimated to be 10.7%. The study also found that urolithiasis prevalence per gender was 6.3% in males and 2.9% in females. The most common clinical presentation of urolithiasis was flank pain at 58.4% (95% CL=, 45.9, 70.8), followed by low back pain at 45.9% (95% CL=, 23.1, 68.8), and nausea/vomiting at 29.9% (95% CI: 1 1.1, 48.8). CONCLUSION: The prevalence of urolithiasis in Sub-Sahara African Countries is increasing even though a remarkable regional variation was observed, with higher predominance in males than females. Common clinical presentations of urolithiasis were flank pain, low back pain, and nausea/vomiting.

Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: a systematic review and meta-analysis with meta-regression of observational studies.

INTRODUCTION: Metformin is the most prescribed medication for type 2 diabetes mellitus (T2DM); there is a well-established link with the elevated incidence of gastrointestinal (GI) adverse events (AE) limiting its administration or intensification. OBJECTIVES: The objective of this systematic review and meta-analysis of observational studies was to evaluate the pooled incidence of GI AE related to metformin use in patients with T2DM. MATERIALS AND METHODS: PUB MED/CINAHL/Web of Science/Scopus were searched from database inception until 29.07.2024 for observational studies in English describing the frequency of GI AE in patients with T2DM treated with metformin. Random-effects meta-analyses were used to derive effect sizes: event rates. RESULTS: From 7019 publications, we identified 211 potentially eligible full-text articles. Ultimately, 21 observational studies were included in the meta-analysis. The prevalence of GI AE was as follows: diarrhea 6.9% (95% CI: 0.038-0.123), bloating 6,2% (95% CI: 0.020-0.177), abdominal pain 5,3% (95% CI: 0.003-0.529), vomiting 2.4% (95%: CI 0.007-0.075), constipation 1.1% (95%: CI 0.001-0.100). The incidence of bloating (coefficient -4.46; p < 0.001), diarrhea (coefficient -1.17; p = 0.0951) abdominal pain (coefficient -2.80; p = 0.001), constipation (coefficient -5.78; p = 0.0014) and vomiting (coefficient -2.47; p < 0.001) were lower for extended release (XR) metformin than metformin immediate release (IR) formulation. CONCLUSIONS: This study highlights the prevalence of GI AE in patients receiving metformin, with a diarrhea predominance, followed by bloating, diarrhea, abdominal pain, constipation, and vomiting. The incidence is lower in patients administered with XR metformin. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289975 , identifier CRD42021289975.

Effects of computerised clinical decision support systems (CDSS) on nursing and allied health professional performance and patient outcomes: a systematic review of experimental and observational studies.

Objective: Computerised clinical decision support systems (CDSS) are an increasingly important part of nurse and allied health professional (AHP) roles in delivering healthcare. The impact of these technologies on these health professionals' performance and patient outcomes has not been systematically reviewed. We aimed to conduct a systematic review to investigate this. Materials and methods: The following bibliographic databases and grey literature sources were searched by an experienced Information Professional for published and unpublished research from inception to February 2021 without language restrictions: MEDLINE (Ovid), Embase Classic+Embase (Ovid), PsycINFO (Ovid), HMIC (Ovid), AMED (Allied and Complementary Medicine) (Ovid), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (Wiley), Cochrane Database of Systematic Reviews (Wiley), Social Sciences Citation Index Expanded (Clarivate), ProQuest Dissertations & Theses Abstracts & Index, ProQuest ASSIA (Applied Social Science Index and Abstract), Clinical Trials.gov, WHO International Clinical Trials Registry (ICTRP), Health Services Research Projects in Progress (HSRProj), OpenClinical(www.OpenClinical.org), OpenGrey (www.opengrey.eu), Health.IT.gov, Agency for Healthcare Research and Quality (www.ahrq.gov). Any comparative research studies comparing CDSS with usual care were eligible for inclusion. Results: A total of 36 106 non-duplicate records were identified. Of 35 included studies: 28 were randomised trials, three controlled-before-and-after studies, three interrupted-time-series and one non-randomised trial. There were ~1318 health professionals and ~67 595 patient participants in the studies. Most studies focused on nurse decision-makers (71%) or paramedics (5.7%). CDSS as a standalone Personal Computer/LAPTOP-technology was a feature of 88.7% of the studies; only 8.6% of the studies involved 'smart' mobile/handheld-technology. Discussion: CDSS impacted 38% of the outcome measures used positively. Care processes were better in 47% of the measures adopted; examples included, nurses' adherence to hand disinfection guidance, insulin dosing, on-time blood sampling and documenting care. Patient care outcomes in 40.7% of indicators were better; examples included, lower numbers of falls and pressure ulcers, better glycaemic control, screening of malnutrition and obesity and triaging appropriateness. Conclusion: CDSS may have a positive impact on selected aspects of nurses' and AHPs' performance and care outcomes. However, comparative research is generally low quality, with a wide range of heterogeneous outcomes. After more than 13 years of synthesised research into CDSS in healthcare professions other than medicine, the need for better quality evaluative research remains as pressing. Funding: This publication was funded by the Health and Social Care Delivery Research programme as a part of award number NIHR127926. This article reports on one component of the research award Effects of computerised clinical decision support systems (CDSS) on nursing and Allied Health Professional performance and patient outcomes: a systematic review and user contextualisation. For more information about this research please view the award page [https://fundingawards.nihr.ac.uk/award/NIHR127926]. DOI: https://doi.org/10.1136/bmjopen-2021-053886.

The chronic wound characterisation study and biobank: a study protocol for a prospective observational cohort investigation of bacterial community composition, inflammatory responses and wound-healing trajectories in non-healing wounds.

INTRODUCTION: Chronic wounds affect 1%-2% of the global population, with rising incidence due to ageing and lifestyle-related diseases. Bacterial biofilms, found in 80% of chronic wounds, and scattered single-cell bacteria may hinder healing. Microbes are believed to negatively impact healing by exacerbating inflammation and host immune response. METHODS AND ANALYSIS: The primary objective of the chronic wound characterisation (CWC) study is to investigate chronic wounds through a prospective observational cohort study exploring bacterial community composition, inflammatory responses and the influence of bacteria on wound-healing trajectories. The CWC study will be investigated through two cohorts: the predictive and in-depth.The predictive cohort includes patients with a chronic wound scheduled for mechanical debridement. The debrided material will be collected for dual RNA sequencing and 16s ribosomal RNA gene sequencing, as well as samples for microbial culturing and a photo to assess the wound. Clinical data is recorded, and healing and/or other clinical endpoints are established through medical records.The in-depth cohort includes and follows patients undergoing split-thickness skin grafting. Extensive sampling (ESwabs, biopsies, tape strips, debrided material and a sample of the skin graft) will be performed on surgery and patients will be seen at two follow-up visits. Samples will be analysed through culturing and next-generation sequencing methods. A biobank will be established comprising longitudinal clinical samples and clinical data. ETHICS AND DISSEMINATION: The study has been approved by the board of health ethics, Capital Region of Denmark, under protocol number H-20032214. The study findings will be disseminated through peer-reviewed publications and showcased at both national and international conferences and meetings within the domains of microbiology, wound healing and infection.

Prediabetes increases the risk of pancreatic cancer: A meta-analysis of longitudinal observational studies.

BACKGROUND: Glycemic disorder is closely related to the risk of pancreatic cancer, but previous studies focused on the influence of diabetes. The aim of this meta-analysis was to investigate the influence of prediabetes, an intermediate state between normoglycemia and diabetes, on the risk of pancreatic cancer. METHODS: Relevant longitudinal observational studies were identified through a search of Medline, Embase, and Web of Science databases. To minimize the influence of between-study heterogeneity, a randomized-effects model was used to pool the results. RESULTS: Nine cohort studies including 26,444,624 subjects were available for the meta-analysis. Among them, 2,052,986 (7.8%) had prediabetes at baseline, and the participants were followed for a mean duration of 5.9 years. It was found that, compared to people with normoglycemia, those with prediabetes had a higher incidence of pancreatic cancer (risk ratio [RR]: 1.42, 95% confidence interval: 1.36 to 1.49, p<0.001) with no statistical heterogeneity (I2 = 0%). Sensitivity analysis performed by excluding one dataset at a time did not significantly change the results (RR: 1.38 to 1.45, p all <0.05). Subgroup analyses indicated that the association between prediabetes and increased risk of pancreatic cancer was not significantly impacted by study characteristics such as study design, location, age, and sex of participants, definition of prediabetes, duration of follow-up, or adjustment for alcohol intake (p for subgroup difference all >0.05). CONCLUSIONS: Prediabetes may be associated with an increased risk of pancreatic cancer compared to normoglycemia.

Chemotherapy effects on mitochondrial function in adipose tissue in oesophageal and gastroesophageal junction adenocarcinomas with or without associated cachexia: protocol for a prospective, comparative observational study (ChiFMeOE).

INTRODUCTION: Cachexia is strongly associated with digestive cancers, particularly oesogastric cancer. Mitochondria in adipose tissue are involved in the regulation of metabolism and physiopathology of cancer cachexia in animal studies. Chemotherapeutic regimens used to control tumour development could also alter mitochondrial function in adipose tissue. We hypothesise that cachexia induces an increase in adipose tissue mitochondrial energy metabolism and that chemotherapy can mitigate this. The purpose of the ChiFMeOE study is to identify adipocyte factors involved in the energy imbalance associated with the cachectic process and their response to chemotherapeutic treatments in patients with oesogastric cancer. METHODS AND ANALYSIS: ChiFMeOE is a single-centre observational study that will prospectively include 60 patients referred to chemotherapy and surgery for oesophageal and gastro-oesophageal junction adenocarcinomas at the University Hospital of Clermont-Ferrand, France. Visceral and subcutaneous adipose tissue biopsies will be collected during surgery scheduled before and after neoadjuvant chemotherapy administration, as well as cachexia and nutritional assessment. The primary outcome is the maximum mitochondrial respiration rate (Vmax) measured by high-resolution respirometry. Secondary outcomes are other mitochondrial parameters (ie, enzymatic activities, proteins content and gene expression), tumour characteristics, nutritional status and body composition. ETHICS AND DISSEMINATION: The study was approved by an independent institutional review board on June 2023 (Comité de protection des personnes Sud-Méditerranée V; 2023-A00582-43) and declared to the French regulatory authority for research. Written informed consent will be obtained prior to patient inclusion. The principal investigator will be notified of any changes in patient's health status requiring a modification of his management and/or treatment during the course of the protocol. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05954117.