Reduced Risk Of Mortality Research Articles

Why Do Only Some Cohort Studies Find Health Benefits From Low-Volume Alcohol Use? A Systematic Review and Meta-Analysis of Study Characteristics That May Bias Mortality Risk Estimates.

Assumptions about alcohol's health benefits profoundly influence global disease burden estimates and drinking guidelines. Using theory and evidence, we identify and test study characteristics that may bias estimates of all-cause mortality risk associated with low-volume drinking. We identified 107 longitudinal studies by systematic review with 724 estimates of the association between alcohol consumption and all-cause mortality for 4,838,825 participants with 425,564 recorded deaths. "Higher-quality" studies had a mean cohort age of 55 years or younger, followed up beyond 55 years, and excluded former and occasional drinkers from abstainer reference groups. "Low-volume" alcohol use was defined as between one drink per week (>1.30 g ethanol/day) and two drinks per day (<25 g ethanol/ day). Mixed linear regression was used to model relative risks (RRs) of mortality for subgroups of higher- versus lower-quality studies. As predicted, studies with younger cohorts and separating former and occasional drinkers from abstainers estimated similar mortality risk for low-volume drinkers (RR = 0.98, 95% CI [0.87, 1.11]) as abstainers. Studies not meeting these quality criteria estimated significantly lower risk for low-volume drinkers (RR = 0.84, [0.79, 0.89]). In exploratory analyses, studies controlling for smoking and/or socioeconomic status had significantly reduced mortality risks for low-volume drinkers. However, mean RR estimates for low-volume drinkers in nonsmoking cohorts were above 1.0 (RR = 1.16, [0.91, 1.41]). Studies with lifetime selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks. Future research should investigate whether smoking status mediates, moderates, or confounds alcohol-mortality risk relationships.

CVD Case Series: Screening and Risk Reduction

Undetected cardiovascular disease is one of the leading causes of complications during pregnancy in the United States. Maternal mortality reviews indicate that lack of suspicion and delays in diagnosis are the primary drivers of CVD-related mortality. Purpose of this study is to examine the effect of implementing the CVD (Cardiovascular Disease) Risk Assessment tool developed by the California Maternal Quality Care Collaborative (CMQCC) team in 2018. Eligibility of patients in the case series was determined through CVD risk screen score of 4 or higher using a standardized stool adopted from the CMQCC. The patient was scored at the point of hospital entry. Factors used in scoring included symptoms, vitals and risk factors. Patients who scored positive were sent for further work up. This included in-depth analysis of other significant clinical factors influencing patient presentation and subsequent management. The CV patient cases presented in this case series illustrate the benefits of early identification and implementation of standardized CVD risk assessment. There are significant benefits in early use of the CV screening tool contributing to mortality risk reduction including continued close antenatal surveillance, postpartum follow-up, and continued collaborative multidisciplinary care. Patients with risk factors underwent continued surveillance and received appropriate specialized follow-up that allowed for improved maternal outcomes. Proper implementation of CVD risk assessment tool for patients who are at-risk of development of CVD in pregnancy can effectively reduce adverse maternal outcomes related to cardiac disease.

CVD Case Series: Screening and Risk Reduction

Undetected cardiovascular disease is one of the leading causes of complications during pregnancy in the United States. Maternal mortality reviews indicate that lack of suspicion and delays in diagnosis are the primary drivers of CVD-related mortality. Purpose of this study is to examine the effect of implementing the CVD (Cardiovascular Disease) Risk Assessment tool developed by the California Maternal Quality Care Collaborative (CMQCC) team in 2018. Eligibility of patients in the case series was determined through CVD risk screen score of 4 or higher using a standardized stool adopted from the CMQCC. The patient was scored at the point of hospital entry. Factors used in scoring included symptoms, vitals and risk factors. Patients who scored positive were sent for further work up. This included in-depth analysis of other significant clinical factors influencing patient presentation and subsequent management. The CV patient cases presented in this case series illustrate the benefits of early identification and implementation of standardized CVD risk assessment. There are significant benefits in early use of the CV screening tool contributing to mortality risk reduction including continued close antenatal surveillance, postpartum follow-up, and continued collaborative multidisciplinary care. Patients with risk factors underwent continued surveillance and received appropriate specialized follow-up that allowed for improved maternal outcomes. Proper implementation of CVD risk assessment tool for patients who are at-risk of development of CVD in pregnancy can effectively reduce adverse maternal outcomes related to cardiac disease.

Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study.

Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown anti-tumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and non-metformin groups, while competing risk regression was performed to assess cancer-specific death. Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with mean age 59.6 (10.3) years received metformin and 164 patients (139 male patients and 25 female patients) with mean age 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P<0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P<0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P<0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P=0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.

Long-term tafamidis efficacy in patients with transthyretin amyloid cardiomyopathy by baseline left ventricular ejection fraction.

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) present with diverse left ventricular ejection fraction (LVEF). This study assessed tafamidis efficacy by baseline LVEF in the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and its long-term extension (LTE) study. Patients were randomized to 30 months of tafamidis or placebo treatment in ATTR-ACT. On completion, patients could join an LTE study to receive tafamidis. All-cause mortality (death, heart transplant, or cardiac mechanical assist device implantation) from baseline to the end of follow-up was assessed in patients continuously treated with tafamidis (80 mg meglumine or 61 mg free acid) or delayed tafamidis treatment (placebo in ATTR-ACT; tafamidis in the LTE study) according to baseline LVEF (<50% or ≥50%). Supportive outcomes were evaluated over a shorter follow-up. Patients with baseline LVEF <50% (n = 177: 88 tafamidis- and 89 placebo-treated) had signs of more severe heart failure, a higher proportion were Black, and had variant ATTR-CM than those with LVEF ≥50% (n = 171: 85 tafamidis- and 86 placebo-treated). At the end of follow-up (median 60-64 months), all-cause mortality was numerically higher in patients with baseline LVEF <50%; however, consistent with supportive findings, continuous tafamidis treatment was associated with a 47% reduction in mortality risk compared with delayed tafamidis treatment in patients with LVEF <50% and ≥50% (hazard ratio 0.53 [95% confidence interval 0.367-0.758]; p < 0.001, and 0.53 [0.344-0.818]; p < 0.01, respectively). Early initiation of tafamidis is associated with reduced mortality in patients with ATTR-CM, irrespective of initial LVEF value. ClinicalTrials.gov NCT01994889, NCT02791230.

Examining the Relationship Between Chronic Pain and Mortality in U.S. Adults

Chronic pain (CP) significantly impacts quality of life and increases noncommunicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing diabetes, depression, and hypertension. International studies suggest higher mortality in CP populations, yet prior U.S. data are inconclusive. To investigate CP's mortality risk, we analyzed National Health Interview Survey and National Death Index data. We hypothesized that individuals with CP and high-impact CP (HICP [≥1 activity limitation]) would exhibit higher mortality rates. National Health Interview Survey provided demographics, pain reporting, lifestyle, and psychosocial data matched with National Death Index mortality records. Chi-square analyses explored the relationships between CP/HICP and demographics, lifestyle factors, psychosocial variables, and mortality. Cox proportional hazards models assessed mortality risk between groups. The weighted sample was 245,899,776; 20% reported CP and 8% HICP, both groups exhibiting higher mortality rates than pain-free individuals (CP: 5.55%, HICP: 8.79%, total: 2.82%). Hazard ratios indicated nearly double the mortality risk for CP and 2.5 times higher risk for HICP compared to those without these conditions. Adjusting for lifestyle and psychosocial factors reduced mortality risk but remained elevated compared with non-CP individuals. Heart disease, malignant neoplasms, and chronic lower respiratory diseases accounted for a higher percentage of deaths in CP cases. CP individuals showed higher rates of smoking, alcohol consumption, obesity, inactivity, depression, anxiety, emotional problems, and sleep disturbances. CP and HICP significantly influence mortality outcomes, leading to excess deaths compared with pain-free individuals. Given the relationship between pain, lifestyle, psychosocial variables, and mortality, further investigations are needed into CP causation and prevention strategies. PerspectiveThis article presents evidence regarding the relationship between CP, HICP, and mortality. Additional findings are discussed regarding the impact of demographics, lifestyle, and psychosocial variables on mortality in those with versus without CP and HICP. These findings are crucial for informing future research, prevention, and healthcare management strategies.

Venous thromboembolism prophylaxis usage among surgical patients in both private and public hospitals in Ethiopia

BackgroundVenous thromboembolism (VTE) remains the commonest preventable cause of death in postoperative patients. VTE prophylaxis significantly reduces mortality risk, yet its utilization remains alarmingly low and variable (6–61 %) worldwide. This study aimed to compare VTE prophylaxis use among adult surgical patients in major hospitals in Addis Ababa, Ethiopia. Materials and methodsA multicenter cross-sectional study was conducted in one private (Myungsung Christian Medical Center Comprehensive Specialized Hospital (MCM CSH)), and two public hospitals (Yekatit 12 Hospital Medical College and Menelik II Referral Hospital). Data was collected by chart review using standardized checklist. Caprini score was used for risk stratification, and associations was assessed using chi-square test with significance set at p < 0.05. ResultsFrom a total of 423 patients, 222 (52.3 %) patients were male. The mean age of the patients is 43.3(±14.7 SD) years. 414 (98 %) patients were at risk for VTE with 257(61 %) having moderate to high risk, but only 31(7.5 %) were on prophylaxis. Prophylaxis use was 12.5 % in MCM CSH, but it was 5.5 % and 5.1 % in Yekatit 12 and Menelik II Referral Hospitals respectively. VTE prophylaxis use was significantly less in public hospitals (p < 0.05). ConclusionsDespite the majority of surgical patients being at risk of developing VTE, VTE prophylaxis remains significantly underutilized across major private and public hospitals in Ethiopia, particularly in public settings. The current study suggests standard risk assessment model implementation to address this significant and understudied risk to patients’ lives.

Tea consumption and risk of all-cause, cardiovascular disease, and cancer mortality: a meta-analysis of thirty-eight prospective cohort data sets.

Tea consumption has been considered beneficial to human health because tea contains phytochemicals such as polyphenols and theaflavins. We conducted a systematic review and meta-analysis on the association between tea consumption and mortality from all causes, cardiovascular disease (CVD), and cancer to provide a quantitative assessment of current evidence. The PubMed, Web of Science, and Scopus databases were searched through April 2024 to identify eligible studies. Random effects models were used to combine study-specific effect estimates (ESs). A total of 38 prospective cohort data sets (from 27 papers) with 1,956,549 participants were included in this meta-analysis. The pooled ESs of the highest versus lowest categories of tea consumption were 0.90 (95% confidence interval [CI], 0.86 to 0.95) for all-cause mortality, 0.86 (95% CI, 0.79 to 0.94) for CVD mortality, and 0.90 (95% CI, 0.78 to 1.03) for cancer mortality. In the dose-response analysis, a non-linear association was observed. The greatest risk reductions were observed for the consumption of 2.0 cup/day for all-cause mortality (ES, 0.91; 95% CI, 0.88 to 0.94) and 1.5 cup/day for cancer mortality (ES, 0.92; 95% CI, 0.89 to 0.96), whereas additional consumption did not show a further reduction in the risk of death. A plateau was observed for CVD mortality at moderate consumption levels (1.5-3.0 cup/day), but a sustained reduction in mortality risk was observed at higher intake levels. Moderate tea consumption (e.g., 1.5-2.0 cup/day) was associated with lower all-cause, CVD, and cancer mortality compared to no tea consumption. Further well-designed prospective studies are needed for a definitive conclusion.

Comparing global trends in gastric cancer and the need for national screening programs: An in-depth literature review

Abstract Introduction Gastric cancer, though experiencing a decline in mortality rates, remains a global concern. This study explores the impact of screening strategies and Helicobacter pylori eradication on gastric cancer incidence and mortality, emphasizing global variations in risk factors and screening programs. Methods A literature review was conducted, searching PubMed and Medline databases for relevant studies. Two distinct searches focused on national screening programs and H. pylori eradication effects, yielding 11,378 studies. Selection criteria refined the studies to 37, emphasizing trial data and recent publications. Statistical analysis, including forest plots, was employed to examine screening outcomes and H. pylori eradication therapy. Results Screening demonstrated a 31% decrease in gastric cancer mortality, with varied incidence outcomes. Population control studies showed an insignificant risk reduction (odds ratio [OR] 0.92), while case–control studies indicated an expected increase in cancer incidence (OR 5.15). Screening intervals of 12 months or less correlated with a 30% mortality risk reduction, and repeated screenings further decreased the risk by 79%. H. pylori eradication therapy exhibited a 56% decrease in cancer odds, emphasizing its significance in both asymptomatic and high-risk individuals. Discussion The study underscores the efficacy of screening methods, with endoscopy and Barium X-ray playing pivotal roles in early detection. Optimal screening intervals and the impact of repeated screenings on mortality risk are highlighted. H. pylori eradication emerges as a critical intervention, with a focus on overcoming challenges such as clarithromycin resistance. Successful screening programs in high-risk regions offer insights for global implementation, with research indicating promising avenues for preventive strategies.

Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data.

Few studies have evaluated the benefits of colorectal cancer (CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model (QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality. We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios (HRs) and absolute risk reductions (ARRs) for CRC incidence and mortality according to risk stratification. During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediate- and high-risk groups [incidence: HR: 0.87, 95% confidence interval (CI): 0.81-0.94; 0.81, 0.73-0.90; mortality: 0.75, 0.64-0.87; 0.70, 0.58-0.85], which composed approximately 60% of the study population. The ARRs (95% CI) were 0.17 (0.11-0.24) and 0.43 (0.24-0.61), respectively, for CRC incidence, and 0.08 (0.05-0.11) and 0.24 (0.15-0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups. After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis.

To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta-analysis. A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality were assessed using Cochrane-endorsed tools. Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78-0.88]). Secondary analysis showed significant risk reduction in all-cause mortality (0.79 [0.72-0.87]) and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta-analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I2 = 10.76%). This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all-cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D.

Oral phosphate binders and incident osteoporotic fracture in patients on dialysis.

End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both calcium and non-calcium-based binders (Mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. Out of 69368 incident dialysis patients, 22326, 5020, 2853, and 39169 were included in the CBPB, NCBPB, mixed, and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared to non-users. Specifically, only the CBPB group showed a reduced risk of vertebral (adjusted hazard ratio (aHR) 0.83 [0.76-0.92]), hip (aHR 0.81 [0.74-0.89]), and distal radius (aHR 0.88 [0.78-0.99]) fractures compared to non-users. This relationship was represented by a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months (aHR 0.9 [0.83-0.99]) and≥6 months (aHR 0.83 [0.78-0.89]), compared to those using CBPB for less than 3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest, and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared to non-users. Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared to non-users.

Survival Analysis and Immune Differences of HIV Long-Term Non-progressors in Xinjiang China: A 12-Year Prospective Cohort Observation

This 12-year cohort study of 80 long-term non-progressors (LTNPs) observed a cumulative follow-up duration of 628.5 person-years. Among them, 60 received antiretroviral therapy (ART) for a total of 418.6 person-years. Twenty-four deaths occurred during the follow-up period, with an average age of 42.36 years and a lowest 8-year survival rate of 0.90. Cox model analysis revealed that the risk of AIDS-related death was 1.47 times higher for non-marital, non-commercial heterosexual transmission than for injection drug use. Treatment initiation at ages 31–40 was correlated with an elevated risk of mortality, while treatment for 3–10 years reduced mortality risks in untreated LTNPs. Flow cytometry observed significant differences in the proportion of NK cells. Long-term ART (> 2 years) before LTNPs developed AIDS symptoms could lower mortality risk and potentially extend lifespan, especially when it was initiated at a younger age without affecting NK cell balance. Epidemiological and immunological studies on ART-treated LTNPs are vital for advancing HIV treatment and achieving functional cures for AIDS individuals.

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults

BackgroundWhether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available.MethodsWe pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome.ResultsOf 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001).ConclusionsIntensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.)

Resiliency and Barriers to Successful Aging Among Middle-Aged Mexican Immigrants Residing in a Rural Agricultural Community.

The Latino population is one of the largest, most diverse, and fastest-growing demographic groups in the United States. Although Latinos enjoy longer life spans and reduced mortality risk relative to non-Hispanic Whites, they have higher rates of chronic health conditions such as diabetes and dementia and live more of their older years with poor health and disability. Such inequities point to the need for this research focused on examining resiliency strategies and barriers to successful aging among various U.S. Latino subgroups. This qualitative study used thematic content analysis to examine resiliency strategies and barriers to successful aging among Mexican immigrant women (n = 40) residing in an underserved agricultural community and entering mid-life (mean = 49 years old). With regards to barriers to successful aging, 3 themes emerged: (1) stressful lifestyle in the United States compared to the participants' home countries; (2) stress from expectations at home; and (3) stress due to work and the various components around work. The following 4 resiliency strategies emerged: (1) family as a motivation for moving forward in life and focusing on the success of children; (2) having a positive mindset; (3) praying to God for strength to overcome obstacles; and (4) self-care. Despite experiencing barriers to successful aging, participants practice various resiliency strategies to age successfully. Because many of the barriers identified are related to poverty-related stressors, systemic solutions addressing the social determinants of health are needed.

Time-dependent efficacy analysis of first-line immunotherapies for advanced non–small cell lung cancer

BackgroundMany randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC.MethodsSeventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison.ResultsWe found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS.ConclusionsBased on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.

Association Between Awareness of Limiting Food Intake and All-cause Mortality: A Cohort Study in Japan.

Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35-69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. The mean follow-up period was 11 years, and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR 0.73; 95% CI, 0.55-0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.

Cohort study finds medications for ADHD reduce mortality risk

Children and adults with attention‐deficit hyperactivity disorder (ADHD) who initiated medication treatment had significantly lower 2‐year mortality rates compared with ADHD patients who did not initiate medication, a cohort study has found. The difference in mortality rates was greater for deaths due to unnatural causes such as accidental poisoning and suicide.

Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Unveiling the relationship between the UGT2B gene family and neoadjuvant treatment response in patients with HER2-positive breast cancer.

e12651 Background: Achieving a pathological complete response (pCR) following neoadjuvant treatment (NAT) in HER2-positive tumors significantly enhances patient survival, resulting in a remarkable 92% reduction in mortality risk. However, it is crucial to identify biomarkers capable of predicting the NAT response, moving towards more personalized medicine. This approach would enable the identification of patients likely to respond to specific therapies, thereby facilitating the implementation of targeted treatment strategies. Our study aims to identify potential molecular biomarkers predictive of NAT response through a comprehensive analysis of differential gene expression in tissue samples from patients with HER2-positive, hormone receptor (HR)-negative breast cancer. Methods: Total RNA was extracted from FFPE tissue samples from two independent cohorts of women diagnosed with localized or locally advanced HER2-positive, HR-negative breast cancer. These patients underwent NAT in several hospitals in Andalusia, Spain. Standard chemotherapy, including taxanes and/or anthracyclines, and targeted anti-HER2 treatment such as trastuzumab and pertuzumab were administered. The patients were stratified into responders (R), achieving pCR, and non-responders (nR). In a discovery cohort (n=20), RNA hybridization using Clariom D microarray was conducted to discern differentially expressed transcripts between R and nR. Subsequently, gene expression patterns, and related pathways involved in NAT response, were analyzed using Transcriptome Analysis Console (TAC). The selected transcripts then underwent validation through quantitative PCR (qPCR) in an independent cohort (n=40). The area under the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the genes as predictive biomarkers. Results: Microarray analysis of the discovery cohort, revealed 954 differentially expressed transcripts between R and nR, following criteria of fold change greater than 1.5 or less than -1.5 and a p-value below 0.05. Among these, 643 were upregulated, while 311 were downregulated in nR compared to R. Bioinformatic analysis and a comprehensive literature review guided the selection of genes UGT2B10, UGT2B11, UGT2B15, UGT2B17, and UGT2B28 for further investigation. Subsequent qPCR analysis in the validation cohort, demonstrated the overexpression of these genes in non-responders, with statistical significance achieved only for UGT2B15. Conclusions: The UGT2B family genes encode enzymes involved in glucuronidation and metabolic pathways associated with drug detoxification and elimination. Our findings suggest that variations in the UGT2B15 expression may impact the metabolism rate of specific drugs, underscoring the necessity for additional research in this area.