A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals

Background Opiate substitution treatment (OST) is the main treatment for people addicted to heroin and other opioid drugs. However, there is limited information on how the delivery of this treatment affects mortality risk. Objectives To investigate the associations of mortality risk with periods during treatment and following cessation of treatment, medication type, co-prescription of other medication and dosing regimens during titration and detoxification. The trends with time of prescribed medication, dose and treatment duration were also explored. Design Prospective longitudinal observational study. Setting UK primary care between 1998 and 2014. Participants A total of 12,780 patients receiving methadone, buprenorphine or dihydrocodeine. Main outcome measures All-cause mortality relating to 657 deaths and drug-related poisoning relating to 113 deaths. Data sources Clinical Practice Research Datalink with linked information on cause of death from the Office for National Statistics. Results For both outcomes, the lowest mortality risk was observed after 4 weeks of treatment and the highest risk was observed in the first 4 weeks following cessation of treatment [e.g. for drug-related poisoning, incidence rate ratio (IRR) 8.15, 95% confidence interval (CI) 5.45 to 12.19]. There was evidence that the treatment period risks varied with OST medication. The largest difference in risk was for the first 4 weeks of treatment for both outcomes, with patients on buprenorphine being at lower risk than those on methadone (e.g. for drug-related poisoning, IRR 0.08, 95% CI 0.01 to 0.48). The co-prescription of benzodiazepines was associated with linearly increasing the risk of drug-related deaths by dose (IRR 2.02, 95% CI 1.66 to 2.47), whereas z-drugs (zolpidem, zopiclone and zaleplon) were associated with increased risk of both all-cause (IRR 1.83, 95% CI 1.59 to 2.12) and drug-related (IRR 3.31, 95% CI 2.45 to 4.47) mortality. There was weak evidence that higher initial and final doses were associated with increased all-cause mortality risk. In the first 4 weeks of treatment, the risk increased by 4% for each 5-mg increment in methadone dose (1-mg increase in buprenorphine) (hazard ratio 1.04, 95% CI 1.00 to 1.09). In the first 4 weeks after treatment ceased, a similar increment in final dose increased the risk by 3% (hazard ratio 1.03, 95% CI 0.99 to 1.07). There were too few deaths to evaluate the effects on drug-related poisoning. The proportion of OST patients receiving buprenorphine increased between 1998 and 2006. Median treatment duration was consistently shorter for buprenorphine than for methadone for each year studied (overall median duration of 48 and 106 days, respectively). Limitations As this was an observational study, the possibility remains of bias from unmeasured factors, which covariate adjustment and inverse probability weighting can eliminate only partially. Conclusions Using buprenorphine as an alternative to methadone may not reduce mortality overall despite resulting in lower IRRs from shorter treatment duration. Clinical guidance needs to consider strengthening warnings about the co-prescription of a range of drugs for OST patients. Future work Our analyses need to be replicated using other clinical data sets in the UK and in other countries. New interventions and trials are required to investigate improving the retention of OST patients in primary care. Funding The National Institute for Health Research Health Services and Delivery Research programme.

Download Full-text

BCG skin reactions by 2 months of age are associated with better survival in infancy: a prospective observational study from Guinea-Bissau

BMJ Global Health ◽

10.1136/bmjgh-2020-002993 ◽

2020 ◽

Vol 5 (9) ◽

pp. e002993

Author(s):

Frederik Schaltz-Buchholzer ◽

Mike Berendsen ◽

Adam Roth ◽

Kristoffer Jarlov Jensen ◽

Morten Bjerregaard-Andersen ◽

...

Keyword(s):

Observational Study ◽

Skin Reaction ◽

Mortality Risk ◽

Prospective Observational Study ◽

Linear Trend ◽

Skin Reactions ◽

Link Type ◽

Guinea Bissau ◽

Cytokine Responses ◽

All Cause Mortality

IntroductionReceiving Bacille Calmette-Guérin (BCG)-Denmark vaccine at birth has been associated with ~40% reductions in all-cause neonatal mortality. We evaluated determinants of BCG skin reaction characteristics by age 2 months and tested the association with subsequent mortality.MethodsProspective observational study amalgamating five trials providing BCG-at-birth that were conducted between 2002 and 2018 in Guinea-Bissau. The reaction status and size were evaluated at home-visits by 2 months of age among 6012 neonates; mortality from 2 to 12 months was assessed at subsequent visits. Reaction determinants were evaluated by binomial regression providing risk ratios (RRs). In Cox-models providing adjusted mortality rate ratios (aMRRs), we assessed the association between (1) having a 2-month reaction (yes/no) and (2) reaction size tertiles and subsequent all-cause mortality risk. A subgroup had their BCG reaction evaluated and were bled at age 4 weeks; their samples underwent in vitro analysis for specific and non-specific cytokine responses.ResultsThe BCG strain was the main determinant for developing a 2-month reaction and the reaction size: the BCG-Russia/BCG-Denmark RR for large-reaction was 0.38 (0.30–0.47) and the BCG-Russia/BCG-Japan RR was 0.61 (0.51–0.72). 5804 infants (96.5%) were reactors by age 2 months; 208 (3.5%) were non-reactors. The 2–12 months mortality risk was 4.8% (10/208) for non-reactors, 2.9% (64/2213) for small reactors, 1.8% (30/1710) for medium reactors and 0.8% (15/1881) for large reactors. The reactor/non-reactor aMRR was 0.49 (0.26–0.95) and there was a linear trend of decreasing mortality with increasing reaction size (p for trend <0.001). BCG reactors had higher 4-week specific and non-specific cytokine responses, responses that were highest among those with large reactions.ConclusionAmong BCG-vaccinated infants, having a BCG skin reaction by age 2 months was associated with markedly better survival, as was the reaction size. Our findings thus support that BCG has substantial effects on all-cause mortality. Emphasising at-birth vaccination with immunogenic BCG strains and revaccinating non-reactors and small reactors could have major public health benefits.Trial registration numbersNCT00146302, NCT00168610, NCT00625482, NCT01989026 and NCT02447536.

Download Full-text

All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A Real-World Observational Study

10.1101/2020.10.13.20211797 ◽

2020 ◽

Author(s):

Javier Mancilla-Galindo ◽

Jorge Óscar García-Méndez ◽

Jessica Márquez-Sánchez ◽

Rodrigo Estefano Reyes-Casarrubias ◽

Eduardo Aguirre-Aguilar ◽

...

Keyword(s):

Clinical Trials ◽

General Population ◽

Observational Study ◽

Mexico City ◽

Mortality Risk ◽

Real World ◽

List Type ◽

Risk Of Death ◽

All Cause Mortality ◽

Critical Patients

ABSTRACTAimTo evaluate all-cause mortality risk in patients with laboratory-confirmed COVID-19 in Mexico City treated with repurposed antivirals and antibiotics.MethodsThis real-world retrospective cohort study contemplated 395,343 patients evaluated for suspected COVID-19 between February 24 and September 14, 2020 in 688 primary-to-tertiary medical units in Mexico City. Patients were included with a positive RT-PCR for SARS-CoV-2; those receiving unspecified antivirals, excluded; and antivirals prescribed in <30 patients, eliminated. Survival and mortality risks were determined for patients receiving antivirals, antibiotics, both, or none.Results136,855 patients were analyzed; mean age 44.2 (SD:16.8) years; 51.3% were men. 16.6% received antivirals (3%), antibiotics (10%), or both (3.6%). Antivirals studied were Oseltamivir (n=8414), Amantadine (n=319), Lopinavir-Ritonavir (n=100), Rimantadine (n=61), Zanamivir (n=39), and Acyclovir (n=36). Survival with antivirals (73.7%, p<0.0001) and antibiotics (85.8%, p<0.0001) was lower than no antiviral/antibiotic (93.6%). After multivariable adjustment, increased risk of death occurred with antivirals (HR=1.72, 95%CI:1.61-1.84) in ambulatory (HR=4.7, 95%CI:3.94-5.62) and non-critical (HR=2.03, 95%CI:1.86-2.21) patients. Oseltamivir increased mortality risk in the general population (HR=1.72, 95%CI:1.61-1.84), ambulatory (HR=4.79, 95%CI:4.01-5.75), non-critical (HR=2.05, 95%CI:1.88-2.23), and pregnancy (HR=8.35, 95%CI:1.77-39.30); as well as hospitalized (HR=1.13, 95%CI:1.01-1.26) and critical patients (HR:1.22, 95%CI:1.05-1.43) after propensity score-matching. Antibiotics were a risk factor in general population (HR=1.13, 95%CI:1.08-1.19) and pediatrics (HR=4.22, 95%CI:2.01-8.86), but a protective factor in hospitalized (HR=0.81, 95%CI:0.77-0.86) and critical patients (HR=0.67, 95%CI:0.63-0.72).ConclusionsNo significant benefit for repurposed antivirals was observed; oseltamivir was associated with increased mortality. Antibiotics increased mortality risk in the general population but may increase survival in hospitalized and critical patients.WHAT IS ALREADY KNOWNCurrent recommendations for using repurposed antivirals and antibiotics for COVID-19 are conflicting.Few antivirals (i.e. lopinavir-ritonavir) have been shown to provide no additional benefit for COVID-19 in clinical trials; other antivirals may be having widespread use in real-world settings without formal assessment in clinical trials.Real-world use of repurposed antivirals and antibiotics for COVID-19 in population-based studies have not been performed; important populations have been left largely understudied (ambulatory patients, pregnant women, and pediatrics).WHAT THIS STUDY ADDSThis is the first real-world observational study evaluating amantadine, rimantadine, zanamivir, and acyclovir for COVID-19; no registered studies to evaluate these drugs exist. Only one study has evaluated risk of death for oseltamivir. Lopinavir-ritonavir have been previously evaluated in clinical trials.Repurposed antivirals and antibiotics were commonly prescribed in 688 ambulatory units and hospitals of Mexico City despite unclear recommendations for their use out of clinical trials.Oseltamivir was associated with increased mortality risk; other repurposed antivirals (zanamivir, amantadine, rimantadine, and acyclovir) had no significant and consistent impact on mortality. Antibiotics were associated with increased mortality risk in the general population but may increase survival in hospitalized and critical patients.

Download Full-text

486 Clinical composite endpoint classification of REVIVE II corresponds to all-cause mortality risk

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(07)60295-1 ◽

2007 ◽

Vol 6 (1) ◽

pp. 106-107

Author(s):

J TEERLINK ◽

L DELGADOHERRERA ◽

R THAKKAR ◽

B HUANG ◽

R PADLEY

Keyword(s):

Mortality Risk ◽

Composite Endpoint ◽

All Cause Mortality

Download Full-text

Faculty Opinions recommendation of Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718293699.793492632 ◽

2014 ◽

Author(s):

Panayiotis Benos

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Observational Study ◽

Nuclear Magnetic Resonance Spectroscopy ◽

Resonance Spectroscopy ◽

All Cause Mortality ◽

Nuclear Magnetic

Download Full-text

Selectivity of beta-blockers, cardiovascular and all-cause mortality in people with hypoglycaemia: An observational study

Nutrition Metabolism and Cardiovascular Diseases ◽

10.1016/j.numecd.2019.01.006 ◽

2019 ◽

Vol 29 (5) ◽

pp. 481-488 ◽

Cited By ~ 1

Author(s):

F. Zaccardi ◽

L.L. Nystrup Husemoen ◽

B.L. Thorsted ◽

D.R. Webb ◽

S.K. Paul ◽

...

Keyword(s):

Observational Study ◽

Beta Blockers ◽

All Cause Mortality

Download Full-text

High School Quality and 56-Year All-Cause Mortality Risk Across Race and Ethnicity

Innovation in Aging ◽

10.1093/geroni/igaa057.1632 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 505-506

Author(s):

Dominika Seblova ◽

Kelly Peters ◽

Susan Lapham ◽

Laura Zahodne ◽

Tara Gruenewald ◽

...

Keyword(s):

High School ◽

Mortality Risk ◽

Race And Ethnicity ◽

Proportional Hazards ◽

School Quality ◽

Cox Proportional Hazards ◽

School Level ◽

Lower Mortality ◽

All Cause Mortality ◽

Race Ethnicity

Abstract Having more years of education is independently associated with lower mortality, but it is unclear whether other attributes of schooling matter. We examined the association of high school quality and all-cause mortality across race/ethnicity. In 1960, about 5% of US high schools participated in Project Talent (PT), which collected information about students and their schools. Over 21,000 PT respondents were followed for mortality into their eighth decade of life using the National Death Index. A school quality factor, capturing term length, class size, and teacher qualifications, was used as the main predictor. First, we estimated overall and sex-stratified Cox proportional hazards models with standard errors clustered at the school level, adjusting for age, sex, composite measure of parental socioeconomic status, and 1960 cognitive ability. Second, we added an interaction between school quality and race/ethnicity. Among this diverse cohort (60% non-Hispanic Whites, 23% non-Hispanic Blacks, 7% Hispanics, 10% classified as another race/s) there were 3,476 deaths (16.5%). School quality was highest for Hispanic respondents and lowest for non-Hispanic Blacks. Non-Hispanic Blacks also had the highest mortality risk. In the whole sample, school quality was not associated with mortality risk. However, higher school quality was associated with lower mortality among those classified as another race/s (HR 0.75, 95% CI: 0.56-0.99). For non-Hispanic Blacks and Whites, the HR point estimates were unreliable, but suggest that higher school quality is associated with increased mortality. Future work will disentangle these differences in association of school quality across race/ethnicity and examine cause-specific mortality.

Download Full-text

Effect of Perceived Social Support on Mortality Rate Among Older Chinese Americans

Innovation in Aging ◽

10.1093/geroni/igaa057.642 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 198-199

Author(s):

Charu Verma ◽

Mengting Li ◽

XinQi Dong

Keyword(s):

Social Support ◽

Mortality Risk ◽

Perceived Social Support ◽

Chinese Americans ◽

Well Being ◽

Time Of Death ◽

All Cause Mortality ◽

Older Chinese ◽

Older Chinese Americans ◽

Over Time

Abstract Most existing studies have examined the relationship between social support and health in cross-sectional data. However, the changing dynamics of social support over time and its relationship with all-cause mortality have not been well explored. Using data from the Pine Study (N = 3,157), this study examined whether social support was associated with time of death at an 8 years follow-up among older Chinese Americans. Social support from a spouse, family members and friend were collected at the baseline using an HRS social support scale. Perceived social support and time of death were ascertained from the baseline through wave 4. Cox proportional hazard models were used to assess associations of perceived support with the risk of all-cause mortality using time-varying covariate analyses. Covariates included age, sex, education, income, and medical comorbidities. All study participants were followed up for 8 years, during which 492 deaths occurred. In multivariable analyses, the results showed that positive family support [HR 0.91; 95% CI (0.86, 0.98)] and overall social support [HR 0.95; 95% CI (0.92,0.98)] were significantly associated with a lower risk of 8-year mortality. Results demonstrate robust association in which perceived positive family and overall social support over time had a protective effect on all-cause mortality risk in older Chinese Americans. Interventions could focus on older adults with low social support and protect their health and well-being. Future studies could further explore why social support from family is different from social support from other sources regarding mortality risk in older Chinese Americans.

Download Full-text

Prognostic Value of Serum Magnesium in Mortality Risk among Patients on Hemodialysis: A Meta-Analysis of Observational Studies

Kidney Diseases ◽

10.1159/000510513 ◽

2020 ◽

pp. 1-10

Author(s):

Hongwei Wu ◽

Qiang Li ◽

Lijing Fan ◽

Dewang Zeng ◽

Xianggeng Chi ◽

...

Keyword(s):

Mortality Risk ◽

Cardiovascular Mortality ◽

Observational Studies ◽

Prognostic Value ◽

Meta Analysis ◽

Serum Magnesium ◽

Cochrane Library ◽

Lower Serum ◽

All Cause Mortality ◽

End Stage

Background: Previous studies have reported that serum magnesium (Mg) deficiency is involved in the development of heart failure, particularly in patients with end-stage kidney disease. The association between serum Mg levels and mortality risk in patients receiving hemodialysis is controversial. We aimed to estimate the prognostic value of serum Mg concentration on all-cause mortality and cardiovascular mortality in patients receiving hemodialysis. Methods: We did a systematic literature search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify eligible studies that reported the prognostic value of serum Mg levels in mortality risk among patients on hemodialysis. We performed a meta-analysis by pooling and analyzing hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We identified 13 observational studies with an overall sample of 42,967 hemodialysis patients. Higher all-cause mortality (adjusted HR 1.58 [95% CI: 1.31–1.91]) and higher cardiovascular mortality (adjusted HR 3.08 [95% CI: 1.27–7.50]) were found in patients with lower serum Mg levels after multivariable adjustment. There was marked heterogeneity (I2 = 79.6%, p < 0.001) that was partly explained by differences in age stratification and study area. In addition, subgroup analysis showed that a serum Mg concentration of ≤1.1 mmol/L might be the vigilant cutoff value. Conclusion: A lower serum Mg level was associated with higher all-cause mortality and cardiovascular mortality in patients receiving hemodialysis.

Download Full-text