[Excess deaths in Argentina during the COVID-19 pandemic: analysis of mortality between 2020 and 2022]. / Exceso de muertes en Argentina durante la pandemia por COVID-19: análisis de la mortalidad entre 2020 y 2022.

Reports of excess mortality during the COVID-19 pandemic in Argentina have been partial and fragmented so far. This study aimed to quantify excess deaths and explore their demographic, temporal, and geographic distribution during the period 2020-2022. Using data from 1 192 963 death records from vital statistics and population projections, expected mortality was estimated using regression models. Excess death was calculated as the difference between observed and expected mortality. An excess of 160 676 deaths (95% CI 146 861 to 174 491) was estimated, representing a rate of 116.9 (95% CI 115.5 to 118.3) additional deaths per 100 000 personyears. Significant heterogeneity was found among the different argentine provinces. The results indicate an uneven impact of the pandemic, with higher excess mortality rates in some regions and more vulnerable age groups. These patterns suggest the need for differentiated strategies of healthcare response and support to the most vulnerable populations in scenarios of new epidemics.

Los reportes del exceso de mortalidad durante la pandemia por COVID-19 en Argentina han sido parciales y fragmentados hasta el momento. Este estudio se propuso cuantificar el exceso de muertes y explorar su distribución demográfica, temporal y geográfica durante el periodo 2020-2022. Utilizando datos de 1 192 963 registros de muertes de estadísticas vitales y proyecciones poblacionales, se estimó la mortalidad esperada mediante modelos de regresión. El exceso de muertes se calculó como la diferencia entre la mortalidad observada y la esperada. Se estimó un exceso de 160 676 muertes (IC 95% 146 861 a 174 491), representando una tasa de 116.9 muertes (IC 95% 115.5 a 118.3) adicionales por cada 100 000 personas-año. Se verificó una significativa heterogeneidad entre las distintas provincias argentinas. Los resultados indican un impacto desigual de la pandemia, con mayores tasas de exceso de mortalidad en algunas regiones y grupos de edad más vulnerables. Estos patrones sugieren la necesidad de estrategias diferenciadas de respuesta sanitaria y apoyo a las poblaciones más vulnerables en escenarios de nuevas epidemias.

Understanding Causes of Death in Patients With Acute Respiratory Distress Syndrome: A Narrative Review.

OBJECTIVES: To provide a comprehensive summary of the published data on cause of death in patients with acute respiratory distress syndrome (ARDS). DATA SOURCES: PubMed (January 2015 to April 2024), bibliographies of relevant articles, and ARDS Network and Prevention & Early Treatment of Acute Lung Injury (PETAL) network websites. STUDY SELECTION: Observational studies and clinical trials that reported on cause of death in greater than or equal to 30 patients with ARDS, not obtained from death certificates. Animal studies, case reports, review articles, study protocols, and studies in pediatrics were excluded. DATA EXTRACTION: Causes of death among ARDS patients who died were extracted and tabulated along with other pertinent study characteristics. DATA SYNTHESIS: We identified 15 observational studies (nine non-COVID ARDS, five COVID-related ARDS; one both) and five clinical trials (all non-COVID ARDS). Mutually exclusive prespecified categories were used for recording the cause of death in only eight studies although studies differed in the categories included and their definitions. When multiple organ failure was a predetermined category, it was the most common cause of death recorded (~50% of deaths), followed by respiratory causes with proportions varying from 16% to 42% depending on nomenclature (e.g., refractory hypoxemia, pulmonary causes) and definitions. However, the largest observational study in non-COVID ARDS (964 deaths), did not include multiple organ failure as a predetermined category, and found that pulmonary failure (42%) and cardiac failure (37%) were the most common causes of death. In COVID-related ARDS observational studies, pulmonary reasons were the most reported cause of death (up to 88%). CONCLUSIONS: Few studies have reported cause of death in patients with ARDS. In those that do, cause of death categories and definitions used are heterogeneous. Further research is needed to see whether a more rigorous and unified approach to assigning and reporting cause of death in ARDS would help identify more relevant endpoints for the assessment of targeted treatments in clinical trials.

Disability-related disparities in health outcomes among newly diagnosed diabetic patients: A retrospective cohort.

BACKGROUND: A distinct gap in the literature persists regarding the health outcome of individuals with Type 2 diabetes who also have disabilities. This study aimed to investigate potential disparities in events occurrence among diabetes patients across various disability stages. METHODS: We conducted a retrospective cohort study on patients newly diagnosed with diabetes in 2013 and 2014, aged ≥ 18 years, and followed them until December 2021, using data from the Korean National Health Insurance database. All-cause mortality and hospitalization for diabetes mellitus and cardio-cerebrovascular diseases (CVD) was assessed. RESULTS: The study included 26,085 patients, encompassing individuals without disabilities and those with physical, visual, hearing and speech, intellectual and developmental, and mental disabilities. After adjustment, individuals with disabilities had a higher risk of all-cause death (adjusted hazard ratio [aHR]: 1.25, 95% CI: 1.07-1.48) compared to those without disabilities. In particular, severe disabilities and hearing and speech disabilities showed significantly higher risks of all-cause death (aHR: 1.40, 95% CI: 1.06-1.85 and aHR: 1.58, 95% CI: 1.17-2.15, respectively), with marginal significance for mild disabilities (aHR: 1.20, 95% CI: 0.99-1.45) and mental disorders (aHR: 1.92, 95% CI: 0.98-3.73). Patients with disabilities also had significantly increased risks of CVD-related first admissions (aHR: 1.30, 95% CI: 1.07-1.56) and diabetes-related first admissions (aHR: 1.31, 95% CI: 1.20-1.43) compared to those without disabilities. CONCLUSIONS: This study underscores the urgent need for public health policies to prioritize individuals with disabilities and diabetes, addressing the disparities in health outcome.

Inflammatory burden index: associations between osteoarthritis and all-cause mortality among individuals with osteoarthritis.

BACKGROUND: The newly described inflammatory burden index (IBI) reflects a patient's inflammatory burden. This study aimed to estimate the association between IBI, osteoarthritis (OA), and all-cause mortality in patients with OA. METHODS: We extracted the data of adults from the National Health and Nutrition Examination Survey database between 1999 and 2018. After using appropriate survey weights to correct for sample bias, we conducted multivariate logistic regression analyses to explore the association between IBI and OA across three models: in the unadjusted model, partially adjusted model (adjusting age, sex, race, education level, marital status, PIR, BMI, smoking status, drinking status, stroke, CVD, DM, and hypertension) and fully adjusted model (which included additional variables: HBA1C, ALT, AST, BUN, TC, and HDL). And the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Similarly, using comparable survey weights and covariates adjustments, we employed Cox proportional hazards regression analysis to investigate the association between IBI and all-cause mortality in the other 3 models. The Cox proportional hazards regression models were fitted to calculate the hazard ratios (HR) and 95% CI of the association between IBI and all-cause mortality. A restricted cubic spline (RCS) was used to explore the nonlinear relationships between association effects. Subgroup analysis was performed to validate the reliability of their effects. RESULTS: In total, 22,343 eligible participants were included. Multiple logistic regression models revealed that participants with the highest IBI had 2.54 times (95%CI, 2.23, 2.90)) higher risk of OA than those with the lowest IBI in Model 1, whereas the OR was 1.21 (95%CI, 1.03, 1.42) in Model 2 and 1.23 (95%CI,1.05, 1.45) in Model 3. Multiple Cox regression models showed participants with the highest IBI had 186% (95%CI, 1.50, 2.31) times risk of developing all-cause death than those with the lowest IBI in Model 1. This trend remained stable in Models 2 (HR,1.54; 95%CI,1.22, 1.95) and 3 (HR, 1.41; 95%CI, 1.10, 1.80). The RCS revealed a significant positive association between IBI and OA risk. With respect to the association between IBI and all-cause mortality, a slight decrease in mortality was observed from the lowest quartile to the second quartile of IBI, and the mortality risk increased with increasing IBI. Subgroup analyses showed that age, cardiovascular disease, and hypertension were pivotal in the association of IBI with all-cause mortality, whereas the association of IBI with OA remained stable after stratification by other factors such as sex, race, education level, marital, smoking, and drinking status, hypertension, and most serological indices. CONCLUSIONS: This study provides evidence of a positive association between IBI, OA, and all-cause mortality. IBI may be a promising signature for assessing the inflammatory burden in patients with OA, which, in turn, is conducive to precise references for high-risk population recognition, anti-inflammatory guidance, and reducing mortality intervention.

Inflammation and all-cause mortality in patients undergoing peritoneal dialysis.

OBJECTIVE: This study aimed to evaluate inflammatory biomarkers in patients undergoing peritoneal dialysis and investigate their association with all-cause mortality or transfer to hemodialysis. METHODS: This prospective cohort study included 43 patients undergoing peritoneal dialysis. Plasma levels of cytokines were measured using flow cytometry and capture enzyme-linked immunosorbent assay. Biomarkers were categorized based on their respective median values. Survival analysis was conducted using the Kaplan-Meier estimator, considering two outcomes: all-cause mortality and transfer to hemodialysis. RESULTS: After adjusting for confounding factors, plasma levels above the median of the levels of CCL2 and plasma, as well as below the median of TNF-α, and the median of dialysate IL-17 levels, were associated with an increased risk of experiencing the specified outcomes after approximately 16 months of follow-up. CONCLUSION: These findings suggest that inflammatory biomarkers may be a valuable tool for predicting all-cause mortality and transfer to hemodialysis in patients undergoing peritoneal dialysis.

Insights from coronial recommendations for preventing natural deaths in sport and recreation in Québec, Canada.

Introduction: This descriptive retrospective study analyzed coronial recommendations for natural deaths in sport and recreation from January 2006 to December 2019 using data from the Bureau du coroner du Québec. Methods: Reports with recommendations were analyzed by sex, age group, cause of death, context, and activity. The nature of recommendations was assessed using a public health-based model. Thematic analysis was conducted following a four-phase approach in which themes developed were emphasized and further connected with existing literature. Results: Reports involving individuals aged 18-24 and reports related to ice hockey were significantly more likely to contain recommendations. Reports related to individuals ≥45 years old, or related to cycling or hunting had higher death frequencies, but relatively low recommendation rates. Most recommendations aligned with the public health-based model but specifying implementation time frames was rare (11.7%). Nearly 60% of coroner's recommendations focused on automated external defibrillator implementation, delivery and training. Discussion: Mitigation of sudden cardiac arrest risk for individuals ≥45 years old, timely treatment of life-threatening arrhythmias especially for activity practiced in remote regions and specifying implementation time frames were identified as improvement areas. The multi-faceted approach to enhancing public access defibrillation developed by the International Liaison Committee on Resuscitation in 2022 addresses recurrent themes covered by coroners and holds the potential to inform evidence-based decision making.

Maternal mortality in Eastern Democratic Republic of Congo: a 10-year multi-zonal institutional death review.

BACKGROUND: Maternal mortality (MM) remains a real scourge that hits hardest in the poorest regions of the world, particularly those affected by conflict. However, despite this worrying reality, few studies have been conducted about MM ratio in the Democratic Republic of Congo (DRC). The study aimed to describe the trends as well as the epidemiological profile and causes of reported institutional maternal deaths between 2013 and 2022 in Eastern DRC. METHODS: A retrospective descriptive study was conducted between March 2023 and August 2023 in eight Health Zones (HZ), five in South Kivu Province (Mwana, Minova, Miti-Murhesa, Kamituga and Idjwi) and three in North Kivu Province (Kirotshe, Karisimbi and Kayna) in the eastern region of the DRC. Our study covers 242 health facilities: 168 health centers (HC), 16 referral health centers (RHCs),50 referral hospitals (RH) and 8 general referral hospitals (GRHs). Data from registers and medical records of maternal deaths recorded in these zones from 2013-2022 were extracted along with information on the number of deliveries and live births. Sociodemographic, clinical parameters, blood and ultrasound tests and suspected causes of death between provinces were assessed. RESULTS: In total, we obtained 177 files on deceased women. Of these, 143 (80.8%) were retained for the present study, including 75 in the 3 HZs of North Kivu and 68 in the 5 HZs of South Kivu. From 2013 to 2022, study sites experienced two significant drops in maternal mortality ratio (MMR) (in 2015 and 2018), and a spike in 2016-2017. Nonetheless, the combined MMR (across study sites) started and ended the 10-year study period at approximately the same level (53 and 57 deaths per 100,000 live births in 2013 and 2022 respectively). Overall, 62,6% of the deaths were reported from secondary hospital. Most deaths were of married women in their thirties (93.5%). Almost half (47.8%) had not completed four antenatal consultations. The main direct causes of death were, in decreasing order of frequency: post-partum haemorrhage (55.2%), uterine rupture (14.0), hypertensive disorders (8.4%), abortion (7.7%) puerperal infections (2.8%) and placental abruption (0.7%). When comparing among provinces, reported abortion-related maternal mortality (14.1% vs 0%) was more frequent in North Kivu than in South Kivu. CONCLUSION: This study imperatively highlights the need for targeted interventions to reduce maternal mortality. By emphasizing the crucial importance of antenatal consultations, intrapartum/immediate post-partum care and quality of care, significant progress can be made in guaranteeing maternal health and reducing many avoidable deaths.

Association of serum calcium, vitamin D, and C-reactive protein with all-cause and cause-specific mortality in an osteoarthritis population in the UK: a prospective cohort study.

BACKGROUND: Osteoarthritis is a prevalent musculoskeletal condition, but the role of specific serum biomarkers, such as calcium, vitamin D, and C-reactive protein (CRP), in predicting mortality among individuals with osteoarthritis remains unclear. METHODS: This observational study analyzed longitudinal data from over 500,000 participants in the UK Biobank, identifying those with osteoarthritis using ICD-9/10 codes or self-reported history. We performed multivariable cox-regression and flexible parametric survival model (FPSM) for survival analysis, with adjustments made through the inverse probability of treatment weight (IPTW) for baseline covariates identified by directed acyclic graphs (DAGs). RESULTS: Of the 49,082 osteoarthritis population, the average age was 60.69 years, with 58.7% being female. During the follow-up period exceeding 15 years, a total of 5,522 people with osteoarthritis died. High serum calcium levels, compared to normal serum calcium levels, were significantly associated with all-cause mortality (hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11, 1.59), cardiovascular diseases (CVD)-related deaths (HR 1.55, 95% CI 1.05, 2.29), and other deaths (HR 1.59, 95% CI 1.20, 2.11). Low serum calcium levels, compared to normal serum calcium levels, was linked with CVD-related deaths (HR 2.06, 95% CI 1.02, 4.14). Vitamin D insufficiency, compared to sufficient vitamin D levels, was correlated with all-cause mortality (HR 1.22, 95% CI 1.13, 1.33), CVD-related deaths (HR 1.43, 95% CI 1.20, 1.72), and other deaths (HR 1.26, 95% CI 1.09, 1.45) but not with cancer-related deaths. High serum CRP levels, compared to normal CRP levels, were associated with all outcomes (all-cause mortality: HR 1.22, 95% CI 1.12, 1.33; CVD-related death: HR 1.24, 95%CI 1.03, 1.49; cancer-related death: HR 1.23, 95% CI 1.09, 1.40; other deaths: HR 1.19, 95%CI 1.03, 1.38). CONCLUSIONS: Both high and low serum calcium levels, elevated CRP, and vitamin D insufficiency are potential predictors of increased mortality risk in the osteoarthritis population. These findings emphasize the importance of monitoring and possibly addressing these serum biomarkers in osteoarthritis populations to improve long-term outcomes. Further studies are needed to understand the underlying mechanisms and to propose therapeutic interventions.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Blood coagulation in Prediabetes clusters-impact on all-cause mortality in individuals undergoing coronary angiography.

BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.

Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study.

BACKGROUND: The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear. METHODS: We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure). RESULTS: 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50-1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37-10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27-4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27-5.03; p = 0.008). CONCLUSIONS: In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Tamoxifen for adults with hepatocellular carcinoma.

RATIONALE: Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent. OBJECTIVES: To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024. ELIGIBILITY CRITERIA: Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis. OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious. RISK OF BIAS: We assessed risk of bias using the RoB 2 tool. SYNTHESIS METHODS: We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE. INCLUDED STUDIES: We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years. SYNTHESIS OF RESULTS: Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials. AUTHORS' CONCLUSIONS: Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD014869.

Development and validation of a nomogram of all-cause mortality in adult Americans with diabetes.

This study aimed to develop and validate a predictive model of all-cause mortality risk in American adults aged ≥ 18 years with diabetes. 7918 participants with diabetes were enrolled from the National Health and Nutrition Examination Survey (NHANES) 1999-2016 and followed for a median of 96 months. The primary study endpoint was the all-cause mortality. Predictors of all-cause mortality included age, Monocytes, Erythrocyte, creatinine, Nutrition Risk Index (NRI), neutrophils/lymphocytes (NLR), smoking habits, alcohol consumption, cardiovascular disease (CVD), urinary albumin excretion rate (UAE), and insulin use. The c-index was 0.790 (95% CI 0.779-0.801, P < 0.001) and 0.792 (95% CI: 0.776-0.808, P < 0.001) for the training and validation sets, respectively. The area under the ROC curve was 0.815, 0.814, 0.827 and 0.812, 0.818 and 0.829 for the training and validation sets at 3, 5, and 10 years of follow-up, respectively. Both calibration plots and DCA curves performed well. The model provides accurate predictions of the risk of death for American persons with diabetes and its scores can effectively determine the risk of death in outpatients, providing guidance for clinical decision-making and predicting prognosis for patients.

Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan.

BACKGROUND: This cohort study determines the predictors for cause-specific and timing of deaths in patients with COVID-19 in Taiwan. METHODS: Patients with laboratory-confirmed COVID-19 admitted to Taipei City Hospital from January 1 to July 31, 2022, were recruited in this cohort. All patients were followed up until death, discharge from the hospital, or August 31, 2022. Early deaths within the first 2 weeks were recorded, and the cause of death was confirmed by the death certificate database of Taiwan. Predictors of cause-specific and timing of deaths of patients with COVID-19 were determined using multinomial Cox proportional hazards regression analysis. RESULTS: Of the 195 (8.0%) patients who died during hospitalization, 147 (84.0%) had COVID-19-specific deaths. Moreover, 54.9% of the deceased patients had early death. After controlling for other covariates, patients aged ≥ 65 years had a higher risk of COVID-19-specific, non-COVID-19-specific, early, and late deaths [adjusted hazards ratio (AHR): 3.85, 6.45, 3.33, and 6.57; 95% confidence interval (CI): 1.91-7.78, 1.17-35.68, 1.51-7.36, and 2.18-19.76, respectively]. Fully vaccinated patients had a lower risk of COVID-19-specific (AHR: 0.68; 95% CI: 0.47-0.98) and early deaths (AHR: 0.54; 95% CI: 0.35-0.84), whereas comorbid patients with chronic obstructive pulmonary disease had a higher risk of non-COVID-19-specific deaths (AHR: 5.43; 95% CI: 1.73-17.03). CONCLUSIONS: This study suggests that prioritizing COVID-19 vaccination and carefully monitoring comorbid patients during hospitalization can reduce the risk of COVID-19-specific and early deaths and non-COVID-19-specific mortalities, respectively.

Comparison of two different frailty screening scales for predicting mortality due to all causes in older inpatients.

OBJECTIVE: This study examines the relationship between two frailty screening tools and 90-day all-cause mortality in geriatric inpatients. METHODS: The study included patients aged ≥60 years who were admitted to the geriatrics unit of a university hospital between June 2021 and August 2022 and whose mortality status and duration of hospitalization data were obtained from the Health Ministry System. During hospitalization, the patients were screened using two different frailty scales: the Simpler Modified Fried Frailty Scale (sMFS) and the Clinical Frailty Scale (CFS). Patients scoring ≥5 on the CFS and ≥3 on the sMFS were considered frail. RESULTS: A total of 84 participants with a mean age of 78.3±7.6 years were included in this study, of which 36.9% were male. Of the total, 60.7% and 89.3% were considered frail according to the CFS and sMFS, respectively, and the prevalence of all-cause mortality within 90 days was 19%. A univariate analysis using the Kaplan-Meier survival method revealed CFS scores to be statistically significantly related to 90-day all-cause mortality (p<0.001), while sMFS scores were not found to be statistically significant (p=0.849). Furthermore, a statistically significant relationship was identified between CFS score and all-cause mortality in multivariate analysis with Cox regression analysis [(p<0.001), hazard ratio (HR): 3.078; (95% confidence interval: 1.746-5.425)]. CONCLUSION: An evaluation of frailty in hospitalized older adults using two different scales revealed the CFS to be superior to the sMFS in predicting all-cause mortality within 90 days.

Causes of sudden unexpected death in infants with and without pre-existing conditions: a retrospective autopsy study.

OBJECTIVE: We investigated sudden unexpected death in infancy (SUDI) autopsy data from 1996 to 2015 inclusive, comparing findings from infants with and without pre-existing medical conditions. DESIGN: Large, retrospective single-centre autopsy series. SETTING: Tertiary paediatric hospital, London, UK. METHODS: Non-identifiable autopsy findings were extracted from an existing research database for infants older than 7 days up to and including 365 days old who died suddenly and unexpectedly (SUDI; n=1739). Cases were classified into SUDI with pre-existing condition (SUDI-PEC) (n=233) versus SUDI without PEC (SUDI non-PEC) (n=929), where PEC indicates a potentially life-limiting pre-existing medical condition. Findings were compared between groups including evaluation of type of PEC and whether the deaths were medically explained (infectious or non-infectious) or apparently unexplained. RESULTS: Median age of death was greater in SUDI-PEC compared with SUDI non-PEC (129 days vs 67 days) with similar male to female ratio (1.4:1). A greater proportion of deaths were classified as medically explained in SUDI-PEC versus SUDI non-PEC (73% vs 30%). Of the explained SUDI, a greater proportion of deaths were non-infectious for SUDI-PEC than SUDI non-PEC (66% vs 32%). SUDI-PEC (infectious) infants were most likely to have respiratory infection (64%), with susceptible PEC, including neurological, prematurity with a PEC, and syndromes or other anomalies. CONCLUSION: SUDI-PEC deaths occur later in infancy and are likely to have their death attributed to their PEC, even in the absence of specific positive autopsy findings. Future research should aim to further define this cohort to help inform SUDI postmortem guidelines, paediatric clinical practice to reduce infant death, and to reduce the risk of overattribution of deaths in the context of a PEC.

Association between cardiovascular health and all-cause mortality risk in patients with osteoarthritis.

BACKGROUND: This study was to explore the relationship between cardiovascular health (CVH) and the risk of all-cause mortality in patients with osteoarthritis (OA). METHODS: This cohort study retrieved the data of 3642 patients with OA aged ≥ 20 years from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). CVH was evaluated based on Life's Essential 8 (LE8) includes diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. The outcome of all-cause mortality was assessed using the death certificate records of participants from the National Death Index. Variables that might affect all-cause mortality were used as covariates. The weighted univariate COX proportional hazards model was used to explore the association between each covariate and all-cause mortality. The weighted univariate and multivariate COX proportional hazards models were used to explore the association between different CVH levels and all-cause mortality. A restricted cubic spline (RCS) curve was plotted to show the association between different CVH levels and all-cause mortality in OA patients. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: Findings show that people with moderate CVH (HR = 0.67, 95% CI = 0.45-0.98) and high CVH (HR = 0.47, 95% CI = 0.26-0.87) were associated with reduced risk of all-cause mortality in patients with OA. The HR of all-cause mortality in patients with OA decreased by 0.12 as per 10 points increase of LE8 score (HR = 0.81, 95% CI = 0.73-0.90). The RCS curve revealed that the HR of all-cause mortality decreased with the increase in LE8 score. The survival probability of patients in the high CVH group was higher than the moderate CVH group and low CVH group (p = 0.002). CONCLUSION: Moderate-to-high CVH is associated with a decreased risk of all-cause mortality in patients with OA. These findings might provide a reference for the formulation of prognosis improvement strategies for the management of patients with OA.

Injury mortality in South Africa: a 2009 and 2017 comparison to track progress to meeting sustainable development goal targets.

BACKGROUND: Injuries, often preventable, prompted urgent action within the United Nations' 2030 Agenda for Sustainable Development Goals (SDGs) to improve global health. South Africa (SA) has high rates of injury mortality, but accurate reporting of official national data is hindered by death misclassification. OBJECTIVE: Two nationally representative surveys for 2009 and 2017 are utilised to assess SA's progress towards SDG targets for violence and road traffic injuries, alongside changes in suicide and under-5 mortality rates for childhood injuries, and compare these estimates with those of the Global Burden of Disease for SA. METHODS: The surveys utilised multi-stage, stratified cluster sampling from eight provinces, with mortuaries as primary sampling units. Post-mortem files for non-natural deaths were reviewed, with additional data from the Western Cape. Age-standardised rates, 95% confidence intervals (CIs), and incidence rate ratios (IRRs) were calculated for manner of death rate comparisons and for age groups. RESULTS: The all-injury age-standardised mortality rate decreased significantly between 2009 and 2017. Homicide and transport remained the leading causes of injury deaths, with a significant 31% decrease in road traffic mortality (IRR = 0.69), from 36.1 to 25.0 per 100 000 population. CONCLUSIONS: Despite a reduction in SA's road traffic mortality rate, challenges to achieve targets related to young and novice drivers and male homicide persist. Achieving SA's injury mortality SDG targets requires comprehensive evaluations of programmes addressing road safety, violence reduction, and mental well-being. In the absence of reliable routine data, survey data allow to accurately assess the country's SDG progress through commitment to evidence-based policymaking.

Main findings The significant decrease in South Africa's injury mortality rates between 2009 and 2017 appears to largely be driven by the significant 31% decrease in road traffic mortality rates.Added knowledge The 2009 and 2017 survey comparison provides an enhanced understanding of the profile for injury-related deaths, compared to misclassified vital statistics data, to track progress towards reaching Sustainable Development Goals.Global health impact for policy and action The significant reduction in road traffic mortality across all age groups suggests South Africa is making progress towards Sustainable Development Goal Target 3.6 for road safety. However, reducing violence, suicide, and newborn and under-5 injury mortality requires more targeted interventions.

The correlation between healthy lifestyle habits and all-cause and cardiovascular mortality in Guangxi.

BACKGROUND: Adherence to healthy lifestyle habits has become a mainstream approach for lessening the burden of cardiovascular disease (CVD) during initial prevention efforts. The purpose of this study was to investigate the prevalence of four healthy lifestyle habits, the associated factors, and their impact on all-cause and cardiovascular mortality among residents of Guangxi Zhuang Autonomous Region. METHODS: From 2015 to 2019, individuals between the ages of 35 and 75 from Guangxi Zhuang Autonomous Region were recruited through the ChinaHeart Million Person Project. Our study examined four healthy lifestyle habits: not smoking, no or moderate amounts of alcohol, sufficient leisure time physical activity (LTPA) and a balanced diet. RESULTS: Out of the 19,969 individuals involved, the majority, 77.3% did not smoke, while 96.7% had limited alcohol intake, 24.5% engaged in sufficient LTPA, 5.5% followed a balanced diet, and merely 1.7% adhered to all four healthy lifestyle habits. Participants who were women, older, nonfarmers, living in cities, with a high income or level of education, or had hypertension or diabetes were more likely to follow all four healthy lifestyle habits (p < 0.001). People who followed the three healthy lifestyle habits had reduced chances of death from all cause (HR 0.34[95% CI:0.15,0.76]) and cardiovascular-related death (HR 0.23 [95% CI: 0.07, 0.68]) (p < 0.01) over a median period of 3.5 years. CONCLUSIONS: In Guangxi Province, the level of adherence to healthy lifestyle habits is very minimal. Therefore, population-specific health promotion strategies are urgently needed.