Provide Risk Estimates Research Articles

Target trial emulation using new comorbidity indices provided risk estimates comparable to a randomized trial

ObjectivesTo quantify the ability of two new comorbidity indices to adjust for confounding, by benchmarking a target trial emulation against the randomized controlled trial (RCT) result. Study Design and SettingObservational study including 18,316 men from Prostate Cancer data Base Sweden 5.0, diagnosed with prostate cancer between 2008 and 2019 and treated with primary radical prostatectomy (RP, n = 14,379) or radiotherapy (RT, n = 3,937). The effect on adjusted risk of death from any cause after adjustment for comorbidity by use of two new comorbidity indices, the multidimensional diagnosis-based comorbidity index and the drug comorbidity index, were compared to adjustment for the Charlson comorbidity index (CCI). ResultsRisk of death was higher after RT than RP (hazard ratio [HR] = 1.94; 95% confidence interval [CI]: 1.70–2.21). The difference decreased when adjusting for age, cancer characteristics, and CCI (HR = 1.32, 95% CI: 1.06–1.66). Adjustment for the two new comorbidity indices further attenuated the difference (HR 1.14, 95% CI 0.91–1.44). Emulation of a hypothetical pragmatic trial where also older men with any type of baseline comorbidity were included, largely confirmed these results (HR 1.10; 95% CI 0.95–1.26). ConclusionAdjustment for comorbidity using two new indices provided comparable risk of death from any cause in line with results of a RCT. Similar results were seen in a broader study population, more representative of clinical practice.

P082 Nephrolithiasis associated with uricosuric therapies for the treatment of gout: a systematic review

Abstract Background/Aims Uric acid nephrolithiasis is a recognised side-effect of uricosuric therapies and a contraindication to their use. The objective of this systematic review was to assess the incidence and risk of nephrolithiasis in people with gout receiving uricosuric therapy. Methods A systematic review was undertaken using MEDLINE, Embase, Cochrane Library, Web of Science and Clinical Trials electronic databases from inception to 16th May 2023. Pre-specified search terms relating to ‘gout’, ‘uricosuric drugs’ and ‘nephrolithiasis’ and their synonyms were used. Title/abstract and full-text screening and data extraction were undertaken independently by two reviewers. Randomised controlled trials (RCTs) and observational cohort studies assessing the incidence and risk of nephrolithiasis in adults with gout treated with uricosuric therapies were included (with or without a non-uricosuric urate-lowering therapy (ULT) comparator group). The Cochrane Risk of Bias (RoB)-2 for randomised trials and the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tools were used to assess the quality of included RCTs and cohort studies respectively. Results 507 articles were identified, of which 22 studies (8 RCTs, 14 cohort studies) were eligible for inclusion. The mean age of participants ranged from 51.2 years (standard deviation (SD) 10.9) to 66.8 years (SD 9.1). Participants were predominantly male (range 69-100%). Length of follow-up ranged from three months to 10 years. Eleven studies included participants with a prior history of nephrolithiasis. Ten studies assessed Benzbromarone monotherapy, five Lesinurad plus xanthine oxidase inhibitor (XOI), four Probenecid, three Sulfinpyrazone and one Lesinurad monotherapy (total 3091 participants). Ten studies included a non-uricosuric comparator group(s) (five placebo plus XOI, four XOI only, and one placebo only (total 1386 participants)), whereas 12 had no comparator group. Most studies assessed nephrolithiasis through clinical adverse event reporting rather than systematic assessment. The incidence of nephrolithiasis ranged from 0.0% to 11.8% in people receiving uricosuric therapy (four studies reported no stone events; incidence 0.1%-5% in seven studies, 5.1-10% in 9, and >10% in two). The incidence of nephrolithiasis ranged from 0.0% to 4.2% in those not receiving uricosurics. No studies calculated the risk of nephrolithiasis between uricosuric-treated and untreated groups. Few studies documented renal stone composition or reported the severity of clinical presentation of nephrolithiasis events. Conclusion Nephrolithiasis is a common side-effect of uricosuric therapy for gout. Future studies should provide risk estimates between uricosuric-treated and untreated groups, describe clinical presentation of stone events and, where possible, assess stone composition. Disclosure C. Dahanayake: None. R. Bajpai: Other; Dr Bajpai is a member of the Versus Arthritis College of Experts. K.M. Jordan: Other; Dr Jordan is a Trustee of the UK Gout Society. M. Lambie: Honoraria; Dr Lambie has received speakers honoraria from Baxter Healthcare and Fresenius Medical Care. Grants/research support; Dr Lambie has received an unrestricted research grant from Baxter Healthcare. E. Roddy: None.

Exposure to Endocrine-Disrupting Chemicals and Congenital Heart Diseases: The Pooled Results Based on the Current Evidence.

The relationships between maternal exposure to endocrine-disrupting chemicals (EDCs) and congenital heart diseases (CHD) are not elucidated yet. The exposure levels of EDCs are generally estimated based on self-reported questionnaires or occupational exposure evaluations in the literature. Therefore, a study based on epidemiological data from human biospecimens is required to provide stronger evidence between maternal exposure to EDC and CHD. Embase, Pubmed, Scopus, and the Cochrane Library databases were searched for related research which provided risk estimates regarding the relationships between maternal EDC exposure and CHD in human offspring. Baseline characteristics and outcomes of CHD were extracted from each included study. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to calculate the overall estimates of CHD. Subgroup and meta-regression analyses were performed to identify the sources of heterogeneity. Bootstrapping techniques were used in analyses where several studies originated from a similar population. A total of seventeen studies were involved in the meta-analyses. Maternal EDC exposure was significantly related to CHD in offspring (OR 2.15; 95%CI 1.64 to 2.83). EDC exposure was significantly associated with septal defects (OR 2.34; 95%CI 1.77 to 3.10), conotruncal defects (OR 2.54; 95%CI 1.89 to 3.43), right ventricular outflow tract obstruction (OR 2.65; 95%CI 1.73 to 4.07), left ventricular outflow tract obstruction (OR 3.58; 95%CI 2.67 to 4.79), anomalous pulmonary venous return (OR 2.31; 95%CI 1.34 to 4.00), and other heart defects (OR 2.49; 95%CI 1.75 to 3.54). In addition, maternal exposure to heavy metals, which included lead (OR 2.19; 95%CI 1.29 to 3.71), cadmium (OR 1.81; 95%CI 1.28 to 2.56), mercury (OR 2.23; 95%CI 1.13 to 4.44), and manganese (OR 2.65; 95%CI 1.48 to 4.74), increased risks for CHD significantly. In conclusion, based on the latest evidence, maternal EDC exposure may increase CHD risks in human offspring, especially in heavy metal exposure conditions.

Prognostic value of left ventricular systolic function before vascular surgery: a systematic review.

Vascular surgery carries a high risk of post-operative cardiac complications. Recent studies have shown an association between asymptomatic left ventricular systolic dysfunction and increased risk of major adverse cardiovascular events (MACE). This systematic review aims to evaluate the prognostic value of left ventricular function as determined by left ventricular ejection fraction (LVEF) measured by resting echocardiography before vascular surgery. This review conformed to PRISMA and MOOSE guidelines. PubMed, OVID Medline and Cochrane databases were searched from inception to 27 October 2022. Eligible studies assessed vascular surgery patients, with multivariable-adjusted or propensity-matched observational studies measuring LVEF via resting echocardiography and providing risk estimates for outcomes. The primary outcomes measures were all-cause mortality and congestive heart failure at 30 days. Secondary outcome included the composite outcome MACE. Ten observational studies were included (4872 vascular surgery patients). Studies varied widely in degree of left ventricular systolic dysfunction, symptom status, and outcome reporting, precluding reliable meta-analysis. Available data demonstrated a trend towards increased incidence of all-cause mortality, congestive heart failure and MACE in patients with pre-operative LVEF <50%. Methodological quality of the included studies was found to be of moderate quality according to the Newcastle Ottawa Checklist. The evidence surrounding the prognostic value of LVEF measurement before vascular surgery is currently weak and inconclusive. Larger scale, prospective studies are required to further refine cardiac risk prediction before vascular surgery.

Prospective evaluation of the Kaiser Permanente prostate cancer risk calculator in biopsy-naïve men with mild PSA elevations.

290 Background: To assess the impact on biopsy outcomes in biopsy-naïve men with mild PSA elevations (&lt;10 ng/ml) when provided risk estimates using a novel prostate cancer risk calculator. Methods: This prospective study was conducted in urology departments in Kaiser Permanente Northern California in men with PSA elevations that were &lt;10 ng/ml between March 2021 and March 2023. Patient variables (age, race, family history of prostate cancer, body mass index, and PSA level) were entered into our validated calculator. Risk estimates for high-grade cancer (Gleason score ≥7) and overall cancer were shared with the patient who accepted or declined the biopsy. We compared age, race, family history for prostate cancer, BMI, PSA level, predicted high-grade and overall cancer risks between those that accepted and those that declined biopsy. The outcomes of those who underwent biopsy were compared to historical data of biopsy-naïve men with PSA elevations &lt;10 ng/ml who underwent biopsy in the three years prior to the Covid pandemic between January 2016 and December 2019 (n=5141). Results: After 24 months, the calculator was used to estimate risk for 1962 biopsy-naïve men with mild PSA elevations. 1455 (74%) accepted the biopsy. Those with a family history for prostate cancer were slightly more likely to accept biopsy. Age (continuous and categorical), and BMI (continuous and categorical) were not associated with decision for biopsy. Similarly, race/ethnicity when analyzed as four categories (White, Black, Asian, Hispanic) or as two categories (Black vs. all others) was not associated with decision for biopsy. The men who accepted the biopsy had higher predicted median high-grade cancer risks (24% [IQR 17-31%] vs. 20% [IQR 14-29%]; p&lt;0.0001) and higher predicted median overall cancer risks (48% [IQR 40-56%] vs 45% [IQR 37-53%], respectively; p&lt;0.0001) than those who declined the biopsy. Compared to the historical group, use of the risk calculator resulted in a biopsy population enriched with high-grade cancer: 29% vs 25%; similar rates of low-grade cancer: 24% vs 24%; and fewer negative biopsies: 47% vs. 51%, respectively; overall p=0.013. Conclusions: In biopsy-naïve men with mild PSA elevations, use of our risk calculator resulted in a biopsy population that had more high-grade cancer and fewer negative biopsies compared to a historical group. Only family history and higher predicted cancer risks by the calculator were associated with biopsy acceptance.

Introducing the original web score calculator GARDENIA risk score for severe coronary artery (re)stenosis

Abstract Background/Introduction There are a large number of scores that are used for cardiovascular risk assessment and different online calculators are used to perform it. Risk prediction models provide risk estimates that can assist our decision making and improve guiding for individual clinical outcomes and personalized preventive care. Purpose GARDENIA score is designed to predict highly suspicious probability of significant coronary stenosis in patients without proven CAD or those who have already been revascularized. Methods GAR²DE²NIA is an acronym that incorporates following parameters : Gender, Age, Renal impairment, Respiratory disease, Diabetes Melittus, Echo abnormalities, ECG abnormalities, New symptoms, Ischaemia, Atrial fibrillation. The pointing scale was formed (-1 to 2) on the personal interpretation of evidence based data and is applied and designed as web calculator. The established cut-off values for the risk of significant coronary stenosis is 4. For values below 4, the probability of significant CAD is low, below 0 is very low, equal or greater than 4 significant CAD is high and above 8 is very high. Results Standard statistical formulas for sensitivity, specificity, PPN and NPV were used ( sensitivity 91,43%, specificity 73,33%, PPV 88,89, NPV 78,57). Estimated pilot sample size of 100 patients, was tested on patients cohort treated at the Institute for Cardiovascular Disease Dedinje in the year of 2022. Conclusion This original score is to be checked throughout everyday clinical practice. It is easy to use. It can help in decision making in risk stratification and further treatment of the patients who has never been to cardiologist before, those who has already been revascularized and are symptomatic again or need any kind of non cardiac surgery and the patients we have doubts about what to do next.GARDENIA score calculator

Ratio of waist circumference to body mass index: A novel predictor of clinical outcome in hypertension patients.

We aim to investigate the influence of waist circumference and body mass index (BMI) on all-cause death and cardiovascular-specific death in patients with hypertension. This prospective cohort study, based on waist circumference and body mass index measurements in patients with hypertension, provided risk estimates of all-cause mortality and cardiovascular events. The waist circumference-to-BMI ratio (WtBR) is an anthropometric measure integrating waist circumference and BMI. We utilized multivariable Cox regression analysis, restricted cubic spline model, Kaplan-Meier plot, random forest analysis, and sensitivity analysis to assess the relationship of WtBR with all-cause mortality. Subsequently, Fine-Gray competing risk regression models were applied to precisely evaluate the probability of cardiovascular-specific death attributed to high WtBR. The results indicate that thea deceased group showed significantly higher WtBR and lower BMI compared with the alive groups (P<.05), while no significant difference was observed in waist circumference (P=.373). When analyzed as continuous, the risk of all-cause death elevated with increasing WtBR in the adjusted model with an HR of 2.42 (95% CI, 2.06-2.85). The restricted cubic spline illustrated an elevated risk of all-cause mortality as WtBR increased (J-shaped curve). Nevertheless, WtBR showed no significant association with cardiovascular-specific death and the prediction model exhibited a reliable performance in the testing set. This study supported that WtBR, an anthropometric measure, is independently associated with all-cause death in hypertensive patients. It's advisable to routinely assess waist circumference in hypertensive patients regardless of BMI, in order to more effectively manage the risk of obesity-related health.

Lung Cancer Risk Attributable to Active Smoking in China: A Systematic Review and Meta-Analysis

ObjectiveNo consensus exists on the relative risk (RR) of lung cancer (LC) attributable to active smoking in China. This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population. MethodsA systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China. Primary articles on LC providing risk estimates with their 95% confidence intervals (CIs) for “ever” “former” or “current” smokers from China were selected. Meta-analysis was used to estimate the pooled RR of active smoking. ResultsForty-four unique studies were included. Compared with that of nonsmokers, the pooled RR (95% CI) for “ever” “former” and “current” smokers were 3.26 (2.79–3.82), 2.95 (1.71–5.08), and 5.16 (2.58–10.34) among men, 3.18 (2.78–3.63), 2.70 (2.08–3.51), and 4.27 (3.61–5.06) among women, and 2.71 (2.12–3.46), 2.66 (2.45–2.88), and 4.21 (3.25–5.45) in both sexes combined, respectively. ConclusionThe RR of LC has remained relatively stable (range, 2–6) over the past four decades in China. Early quitting of smoking could reduce the RR to some extent; however, completely refraining from smoking is the best way to avoid its adverse effects.

A Bayesian approach to predictive uncertainty in chemotherapy patients at risk of acute care utilization.

Machine learning (ML) predictions are becoming increasingly integrated into medical practice. One commonly used method, ℓ1-penalised logistic regression (LASSO), can estimate patient risk for disease outcomes but is limited by only providing point estimates. Instead, Bayesian logistic LASSO regression (BLLR) models provide distributions for risk predictions, giving clinicians a better understanding of predictive uncertainty, but they are not commonly implemented. This study evaluates the predictive performance of different BLLRs compared to standard logistic LASSO regression, using real-world, high-dimensional, structured electronic health record (EHR) data from cancer patients initiating chemotherapy at a comprehensive cancer centre. Multiple BLLR models were compared against a LASSO model using an 80-20 random split using 10-fold cross-validation to predict the risk of acute care utilization (ACU) after starting chemotherapy. This study included 8439 patients. The LASSO model predicted ACU with an area under the receiver operating characteristic curve (AUROC) of 0.806 (95% CI: 0.775-0.834). BLLR with a Horseshoe+prior and a posterior approximated by Metropolis-Hastings sampling showed similar performance: 0.807 (95% CI: 0.780-0.834) and offers the advantage of uncertainty estimation for each prediction. In addition, BLLR could identify predictions too uncertain to be automatically classified. BLLR uncertainties were stratified by different patient subgroups, demonstrating that predictive uncertainties significantly differ across race, cancer type, and stage. BLLRs are a promising yet underutilised tool that increases explainability by providing risk estimates while offering a similar level of performance to standard LASSO-based models. Additionally, these models can identify patient subgroups with higher uncertainty, which can augment clinical decision-making. This work was supported in part by the National Library Of Medicine of the National Institutes of Health under Award Number R01LM013362. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Is parental unemployment associated with increased risk of adverse childhood experiences? A systematic review and meta-analysis.

Unemployment has adverse consequences for families and can put children at risk of harm. This study presents a systematic review and meta-analysis of global evidence on associations between parental unemployment and adverse childhood experiences (ACEs). Systematic literature searches across four databases identified cross-sectional, cohort or case-control studies measuring associations between parental employment and individual or cumulative ACEs in children. Available risk estimates were extracted and pooled odds ratios calculated using random-effects models. Of 60 included studies, 37 provided risk estimates suitable for pooling across seven ACE types. Paternal/any parental unemployment was associated with a 29% increased risk of sexual abuse, 54% increased risk of neglect, 60% increased risk of physical abuse and around 90% increased risk of child maltreatment and parental mental illness. No associations were found between maternal unemployment and ACEs. Pooling estimates from representative general population studies also identified increased risk of child maltreatment with paternal/any parental unemployment (82%) but not maternal unemployment. Children who grow up with parental unemployment can be at increased risk of ACEs. A combination of socioeconomic measures to increase employment opportunities and parental support targeting fathers and mothers may help break multigenerational cycles of abuse and deprivation.

Associations between fine particulate matter and colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer (CRC) is the second deadliest cancer worldwide. The impact of fine particulate matter (PM2.5) on many diseases is a global concern, yet its association with CRC is unclear. This study aimed to assess the effect of PM2.5 exposure on CRC. We searched PubMed, Web of Science, and Google Scholar databases for population-based articles published before September 2022, providing risk estimates with 95% confidence intervals (CI). Among 85,743 articles, we identified 10 eligible studies across multiple countries and regions in North America and Asia. We calculated the overall risk, incidence and mortality and performed subgroup analyses according to countries and regions. The results revealed an association between PM2.5 and increased risk of CRC (total risk, 1.19 [95% CI 1.12-1.28]; incidence, OR=1.18 [95% CI 1.09-1.28]; mortality, OR=1.21 [95% CI 1.09-1.35]). The elevated risks of CRC associated with PM2.5 were different across countries and regions, at 1.34 [95% CI 1.20-1.49], 1.00 [95% CI 1.00-1.00], 1.08 [95% CI 1.06-1.10], 1.18 [95% CI 1.07-1.29], 1.01 [95% CI 0.79-1.30], in the United States, China, Taiwan, Thailand, and Hong Kong, respectively. Incidence and mortality risks were higher in North America than those in Asia. In particular, the incidence and mortality were highest in the United States (1.61 [95% CI 1.38-1.89] and 1.29 [95% CI 1.17-1.42], respectively) than those in other countries. This study is the first comprehensive meta-analysis to find a strong association between PM2.5 exposure and increased CRC risk.

Gar²De²Nia Risk Score as a New Scoring for Severe Coronary Artery Restenosis and It’s Introducing as a Web Score CalculatorPilot Study

Objectives: Gar²De²Nia score is designed to predict highly suspicious probability of significant coronary stenosis in patients without proven CAD or those who have already been revascularized. Background: There are a large number of scores that are used for cardiovascular risk assessment and different online calculators are used to perform it. Risk prediction models provide risk estimates that can assist our decision making and improve guiding for individual clinical outcomes and personalized preventive care. Methodology: Gar²De²Nia is an acronym that incorporates following parameters: Gender, Age, Renal impairement, Respiratory disease, Diabetes Melittus, Echo abnormalities, ECG abnormalities, new symptoms, Ischaemia, Atrial fibrillation. The pointing scale was formed (-1 to 2) on the personal interpretation of evidence based data and is applied and designed as web calculator. The established cut-off values for the risk of significant coronary stenosis are 4. For values below 4, the probability of significant CAD is low, below 0 is very low, equal or greater than 4 significant CAD is high and above 8 is very high. https://www.gardenia.estavela.in.rs Results: Standard statistical formulas for sensitivity, specificity, PPN and NPV were used (sensitivity 91, 43%, specificity 73, 33%, PPV 88, 89, NPV 78, 57). Estimated pilot sample size of 100 patients, was tested on patients cohort treated at the Institute for Cardiovascular Disease Dedinje in the year of 2022. Conclusion: This original score is to be checked throughout everyday clinical practice. It is easy to use. It can help in decision making in risk stratification and further treatment of the patients who has never been to cardiologist before, those who has already been revascularized and are symptomatic again or need any kind of non-cardiac surgery and the patients we have doubts about what to do next.

Alcohol use and the gender-specific risk of suicidal behavior: a systematic review and meta-analysis protocol

BackgroundAlcohol use is an important risk factor for suicidal behavior, with a heightened risk found among women. The objective of this study is to determine the gender-specific risk of suicidal behaviors (suicide attempt and death by suicide) for different levels and dimensions of alcohol use—i.e., for (1) average alcohol volume consumed, (2) binge drinking, and (3) individuals with an alcohol use disorder.MethodsWe will systematically search the available literature for primary studies on the risk relationships specified above. Using a predetermined set of keywords, a comprehensive systematic literature search will be conducted in the following electronic databases: Embase, PsycINFO, PubMed, and Web of Science. The basic inclusion criteria will be (1) an original, quantitative (cohort, case–control or cross-sectional) study; with (2) a measure of risk of at least one dimension of our alcohol exposures in relation to at least one of our outcomes of interest (suicide attempt or death by suicide), and its corresponding measure of variability is reported (or sufficient data to calculate these); and (3) estimates of risk stratified by gender. Studies (1) that use only qualitative labels of alcohol use, and (2) where suicide attempt and non-suicidal self-harm cannot be disaggregated will be excluded. There will be no restrictions on language, geographical region, or year of publication. Two reviewers will independently perform the search and systematic assessment of each identified study and subsequent extraction of data. Categorical random-effects meta-analyses will be conducted to obtain gender-specific pooled risk estimates. Risk of bias will be assessed using the Risk of Bias In Non-randomised Studies—of Interventions tool and the Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the quality of evidence.DiscussionThis study will synthesize all available data on the gender-specific relationship between various dimensions of alcohol use and suicidal behavior simultaneously in a coherent framework. We will provide risk estimates with the detail needed to better understand the respective risk relationships and appreciate the burden of alcohol-attributable suicide.Systematic review registrationPROSPERO CRD42022320918.

Microbiological risk ranking of foodborne pathogens and food products in scarce-data settings

In the absence of epidemiological, microbiological or outbreak data, systematic identification of the hazards and food products posing the higher risk to the consumers is challenging. It is usually in Low- and Middle-Income Countries (LMICs), where the burden of foodborne disease is highest that data tend to be particularly scarce. In this study, we propose qualitative risk-ranking methods for pathogens and food products that can be used in settings where scarcity of data on the frequency/concentration of pathogens in foodstuff is a barrier towards the use of classical risk assessment frameworks. The approach integrates the existing knowledge on foodborne pathogens, manufacturing processes and intrinsic/extrinsic properties of food products with key context-specific information regarding the supply chain(s), characteristics of the Food Business Operators (FBOs) and cultural habits to identify: (i) the pathogens that should be considered as a “High” food safety priority and (ii) the food products posing the higher risk of consumer exposure to microbiological hazards via the oral (ingestion) route. When applied to the dairy sector of Andhra Pradesh (India) as a case study, Shiga toxin-producing E. coli , Salmonella spp., S. aureus and L. monocytogenes were identified as a “High” food safety priority across all FBOs. C. sakazakii was identified as a “High” priority for the FBOs producing infant formula/milk powder whilst Shigella spp., and Cryptosporidium spp. a “High” priority when considering the FBOs operating in the unregulated sector. Given the diversity of dairy products considered in the assessment, cluster analysis was used to identify products that shared similar intrinsic/extrinsic features known to drive the microbiological risk. The risk ranking was then done integrating the results of the cluster analysis with context-specific information. Products manufactured/retailed by FBOs in the informal market were considered as posing a “High” risk for the consumers due to a widespread lack of compliance to sanitary regulations. For dairy products produced by FBOs operating in the middle and formal end of the formal-informal spectrum, the risk of consumers exposure to microbiological hazards ranged from “Moderate” to “Extremely low” depending on the FBO and the intrinsic/extrinsic properties of the products. While providing risk estimates of lower precision if compared to data-driven risk assessments, the proposed method maximises the value of the information that can be easily gathered in LMICs and provide informative outputs to support food safety decision-making in contexts where resources to be allocated for prevention of foodborne diseases are limited and the food system is complex. • A method for risk ranking of pathogens/food products in settings where microbiological data is lacking is proposed. • Informed, systematic and transparent food safety decisions can be made in absence of microbiological data. • Sociocultural behaviours & context-specific characteristics of the food chain are major drivers for exposure to microbial hazards

Serious adverse events after cessation of nucleos(t)ide analogues in individuals with chronic hepatitis B: A systematic review and meta-analysis

The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue. We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation. The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity (I 2= 54%, p <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity (I 2= 0.00%, p= 1.00). Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation. Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.

Risk for severe outcomes of COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany

Although children and adolescents have a lower burden of SARS-CoV-2-associated disease compared to adults, assessing the risk for severe outcomes among SARS-CoV-2-infected children remains difficult due to a high rate of undetected cases. We combine data from three data sources — a national seroprevalence study (the SARS-CoV-2 KIDS study), the nationwide, state-based reporting system for PCR-confirmed SARS-CoV-2 infections in Germany, and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or pediatric inflammatory multisystem syndrome (PIMS-TS, also known as MIS-C) — in order to provide estimates on the risk of hospitalization for COVID-19-related treatment, intensive care admission, and death due to COVID-19 and PIMS-TS in children. The rate of hospitalization for COVID-19-related treatment among all SARS-CoV-2 seropositive children was 7.13 per 10,000, ICU admission 2.21 per 10,000, and case fatality was 0.09 per 10,000. In children without comorbidities, the corresponding rates for severe or fatal disease courses were substantially lower. The lowest risk for the need of COVID-19-specific treatment was observed in children aged 5–11 without comorbidities. In this group, the ICU admission rate was 0.37 per 10,000, and case fatality could not be calculated due to the absence of cases. The overall PIMS-TS rate was 2.47 per 10,000 SARS-CoV-2 infections, the majority being children without comorbidities.Conclusion: Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5–11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in the overall disease burden among all pediatric age groups.What is Known:• SARS-CoV-2-associated burden of disease in children is considered to be low, but accurate risk estimates accounting for clinically undiagnosed infections are lacking.• Asymptomatic SARS-CoV-2 infections are common in children.What is New:• We provide risk estimates for hospitalization for COVID-19-related treatment, ICU admission, death from COVID-19, and PIMS-TS for children with SARS-CoV-2 infections by pooling different data sources.• The risk for PIMS-TS exceeds the risk for severe COVID-19 in all age groups; the risk for severe COVID-19 is the lowest in 5–11 years old.

The Association between Migraine and Fetal-Type Posterior Cerebral Artery in Patients with Ischemic Stroke

Objective: The aim of the study was to determine if migraine is associated with fetal-type posterior cerebral artery (PCA) in patients with ischemic stroke. Method: In this cross-sectional study, patients with acute ischemic stroke were enrolled from two hospitals. The history of migraine headache was evaluated during a face-to-face interview. The variants of fetal-type PCA were assessed with MRA, CTA, or DSA. Patients with and without migraine were compared in terms of fetal-type PCA status and other clinic characteristics. Multivariate logistic regression analyses were performed to adjust for confounders and provide risk estimates for observed associations. Result: In 750 patients qualified for analysis, 85 (11.3%) were determined with migraine. Patients with migraine had a higher proportion of female gender (51.8% vs. 31.0%, p < 0.001), hypertension (72.9% vs. 57.7%, p = 0.007), and fetal-type PCA (36.5% vs. 20.1%, p = 0.001), while lower proportion of current smoking (25.9% vs. 38.3%, p = 0.025) than patients without migraine. National Institutes of Health Stroke Scale (NIHSS) score (3 vs. 2, p = 0.016) was also higher in migraineurs than in non-migraineurs. After adjustment for confounders, fetal-type PCA status was independently associated with migraine (odds ratio [OR] = 2.06; 95% confidence interval [CI], 1.25–3.38; p = 0.005). Other factors associated to migraine included female gender (OR = 2.03; 95% CI, 1.13–3.62; p = 0.017), hypertension (OR = 1.97; 95% CI, 1.17–3.34; p = 0.011), and NIHSS score (OR = 1.08; 95% CI, 1.01–1.16; p = 0.018). Conclusion: Migraine was associated with fetal-type PCA in patients with ischemic stroke. This finding supported the hypothesis that vascular mechanisms get involved in the migraine-stroke association.

Risk Associated with Common Procedures Performed in a Referral Allergy Clinic

Allergists perform a range of procedures that have a risk of anaphylaxis. Risk estimates from controlled trials may vary from clinical practice. The aim of this study is to provide risk estimates for procedures performed in our allergy clinic.

The contribution of germline DNA damage response mutations on prostate cancer risk and prognosis: A UK Biobank whole-exome analysis.

67 Background: Germline mutations in DNA Damage Response (DDR) genes such as BRCA2 and ATM have been associated with prostate cancer risk and aggressiveness. These associations are largely based on studies that ascertain for cancer diagnosis and family history and provide risk estimates with limited population-level accuracy. Here we evaluate the clinical significance of germline pathogenic variants in 20 DDR genes and a high-risk susceptibility coding variant in HOXB13 using whole exome sequences from (1) the UK Biobank (UKBB), a population-based cohort (300,000 participants) and (2) patients recruited in AZ clinical trials. Methods: Whole exomes from 6,987 prostate cancer patients (5,921 UKBB and 1,066 AZ) and 88,499 cancer-free males were analysed. Known and novel pathogenic variants were identified and associations with disease risk, age of onset, family history, response to hormonal therapy and overall survival were estimated (multiplicity corrected P value &lt; 0.005). Results: HOXB13 G48E (1.36%), ATM (1.03%) and BRCA2 (0.99%) were the largest contributors to prostate cancer risk, each conferring an increase of ~4-fold, followed by CHEK2 with a moderate contribution (0.46%). No significant contributions to prostate cancer risk were observed for any of the other genes analysed. Family history of prostate cancer was not significantly enriched in any of the gene subpopulations of prostate cancer carriers and compared with non-carriers, there was no significant difference in the median age of disease onset. Analysis of clinical outcomes showed that BRCA2 carriers had a 4-fold increased risk of death (Cox PH HR p = 4.11E-12) and poorer overall survival (Log-Rank p = 4.60E-14), with 88% dying from prostate cancer compared to 49% of non- BRCA2 carriers (UKBB analysis). BRCA2 pathogenic mutations were also associated with early failure to hormonal therapy (Cox PH HR 2.38; p = 9.48E-04; AZ cohort analysis). HOXB13, ATM and CHEK2 mutations were not significantly associated with clinical outcomes. Conclusions: This is the largest study to date providing population-based estimates of prostate cancer risk and prognosis, highlighting BRCA2 carriers as a population in clinical need of early identification and targeted intervention. Updated analyses with data from the full 450,000 UKBB participants (9,000 prostate cancers) will be presented.

Prognostic implications of atrial fibrillation in patients with stable coronary artery disease: a systematic review and meta-analysis of adjusted observational studies.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. Despite the frequent coexistence with coronary artery disease (CAD), the prognostic independent implication of AF in patients with stable CAD remains controversial. Our aim was to perform a pairwise meta-analysis of adjusted observational studies comparing cardiovascular outcomes in patients with stable CAD with and without concomitant AF, in search of AF-specific prognostic implications. We performed random effect meta-analysis of binary outcome events in studies comparing stable CAD patients with versus without AF providing risk estimates adjusted for confounding variables. Literature search was performed in PubMed/MEDLINE and Google Scholar. Death was the primary endpoint of the analysis, while myocardial infarction, coronary revascularization and stroke secondary endpoints. 5 studies were included in the meta-analysis, encompassing a total of 30230 stable CAD patients (2844 with AF, 27386 without AF). Stable CAD patients with AF presented an independent increased risk of death (HR 1.39, 95% CI: 1.17-1.66) and stroke (HR 1.88, 95% CI: 1.45-2.45) compared to those without AF. Instead, risk of myocardial infarction (HR 0.90, 95% CI: 0.66-1.22) and coronary revascularization (HR 0.96, 95% CI: 0.79-1.16) did not differ in stable CAD patients with and without the arrhythmia. In patients with stable CAD, AF exerts an independent negative prognostic effect, increasing the risk of death and stroke. However, the small number of eligible studies included in this analysis highlights the astonishing lack of data regarding prognostic implications of concomitant AF in patients with stable CAD.