Depression, diabetes, their comorbidity and all-cause and cause-specific mortality: a prospective cohort study

Aims/hypothesis: To investigate the risk of all-cause and cause-specific mortality among participants with neither, one, or both of diabetes and depression in a large prospective cohort study in the United Kingdom. Methods: Our study population included 499,830 UK Biobank participants without schizophrenia and bipolar disorder at baseline. Type 1 or type 2 diabetes and depression were identified using self-reported diagnoses, prescribed medication and hospital records. Mortality was identified from death records using the primary cause of death to define cause-specific mortality. We performed Cox proportional hazards models to estimate the risk of all-cause mortality and mortality due to cancer, circulatory disease and causes of death other than circulatory disease or cancer among participants with either depression (n=41,791) or diabetes alone (n=22,677) and with comorbid diabetes and depression (n=3,597), compared to the group with neither condition (n=431,765) adjusting for sociodemographic and lifestyle factors, comorbidities, and history of CVD or cancer. We investigated for interaction between diabetes and depression. Results: During a median of 6.8 (IQR: 6.1 - 7.5) years of follow-up, there were 13,724 deaths (cancer (n=7,976), circulatory disease (n=2,827), and other causes (n=2,921)). Adjusted hazard ratios of all-cause mortality and mortality due to cancer, circulatory disease and other causes were highest among people with comorbid depression and diabetes (HRs 2.16, 95% CI 1.94 - 2.42; 1.62, 95% CI 1.35 - 1.93; 2.22 95% CI 1.80 - 2.73 and 3.60, 95% CI 2.93 - 4.42, respectively). Among those with comorbid diabetes and depression, the risks of all-cause, cancer and other mortality exceeded the sum of the risks due to diabetes and depression alone. Conclusions/interpretation: We confirmed the negative impact of depression and diabetes on mortality outcomes, and also identified that comorbid depression and diabetes had synergistic effects on all-cause mortality which was largely driven by deaths due to cancer and causes other than circulatory disease and cancer.

Dementia and autopsy-verified causes of death in racially-diverse older Brazilians

Background While dementia has been associated with specific causes of death, previous studies were relatively small autopsy series or population-based studies lacking autopsy confirmation and were restricted to Non-Latinx Whites. Here, we examine the association of dementia with autopsy-verified causes of death in racially-diverse older Brazilians. Methods As part of the Pathology, Alzheimer´s and Related Dementias Study (PARDoS), a community-based study in Brazil, we included 1941 racially-diverse deceased, 65 years or older at death. We conducted a structured interview with legal informants including the Clinical Dementia Rating (CDR) Scale for dementia proximate to death. Causes of death were assessed after full-body autopsy and macroscopic examination of the brain, thoracic and abdominal/pelvic organs. Up to four causes of death were reported for each decedent. Causes of death were classified as circulatory, infectious, cancer and other. Logistic regression was used to determine associations of dementia with cause of death, controlling for age, sex, race, and education. Results Dementia was associated with a higher odds of an infectious cause of death (OR = 1.81, 95%CI:1.45–2.25), and with a lower odds of a circulatory disease as cause of death (OR = 0.69, 95%CI:0.54–0.86) and cancer as cause of death (OR = 0.41, 95%CI:0.24–0.71). Dementia was associated with a higher odds of pneumonia (OR = 1.92, 95%CI:1.53–2.40) and pulmonary embolism (OR = 2.31, 95%CI:1.75–3.05) as causes of death and with a lower odds of acute myocardial infarction (OR = 0.42, 95%CI:0.31–0.56) and arterial disease (OR = 0.76, 95%CI:0.61–0.94) as causes of death. Conclusion Racially-diverse older Brazilians with dementia had a higher odds of an infectious cause of death and a lower odds of cancer and circulatory disease as causes of death than those without dementia.

Understanding the Patterns of Serological Testing for COVID-19 Pre- and Post-Vaccination Rollout in Michigan

Testing for SARS-CoV-2 antibodies is commonly used to determine prior COVID-19 infections and to gauge levels of infection- or vaccine-induced immunity. Michigan Medicine, a primary regional health center, provided an ideal setting to understand serologic testing patterns over time. Between 27 April 2020 and 3 May 2021, characteristics for 10,416 individuals presenting for SARS-CoV-2 antibody tests (10,932 tests in total) were collected. Relative to the COVID-19 vaccine roll-out date, 14 December 2020, the data were split into a pre- (8026 individuals) and post-vaccine launch (2587 individuals) period and contrasted with untested individuals to identify factors associated with tested individuals and seropositivity. Exploratory analysis of vaccine-mediated seropositivity was performed in 347 fully vaccinated individuals. Predictors of tested individuals included age, sex, smoking, neighborhood variables, and pre-existing conditions. Seropositivity in the pre-vaccine launch period was 9.2% and increased to 46.7% in the post-vaccine launch period. In the pre-vaccine launch period, seropositivity was significantly associated with age (10 year; OR = 0.80 (0.73, 0.89)), ever-smoker status (0.49 (0.35, 0.67)), respiratory disease (4.38 (3.13, 6.12)), circulatory disease (2.09 (1.48, 2.96)), liver disease (2.06 (1.11, 3.84)), non-Hispanic Black race/ethnicity (2.18 (1.33, 3.58)), and population density (1.10 (1.03, 1.18)). Except for the latter two, these associations remained statistically significant in the post-vaccine launch period. The positivity rate of fully vaccinated individual was 296/347(85.3% (81.0%, 88.8%)).

Hypertension and the Risk of All-Cause and Cause-Specific Mortality: An Outcome-Wide Association Study of 67 Causes of Death in the National Health Interview Survey

Background. Few studies have assessed the association between hypertension and risk of detailed causes of death. We investigated the association between hypertension and all-cause mortality and 67 causes of death in a large cohort. Methods. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for self-reported hypertension vs. no hypertension and mortality. Adults aged ≥18 years ( n = 213798 ) were recruited in 1997-2004 and followed through December 31, 2006. Results. During 5.81 years of follow-up, 11254 deaths occurred. Self-reported hypertension vs. no hypertension was associated with increased risk of all-cause mortality ( HR = 1.25 , 95% CI: 1.19-1.31) and mortality from septicemia (HR =1.66, 1.06-2.59), other infectious parasitic diseases ( HR = 2.67 , 1.09-6.51), diabetes mellitus ( HR = 1.97 , 1.45-2.67), circulatory disease ( HR = 1.49 , 1.37-1.61), hypertensive heart disease ( HR = 3.23 , 2.00-5.20), ischemic heart disease ( HR = 1.35 , 1.23-1.49), acute myocardial infarction ( HR = 1.50 , 1.27-1.77), other chronic ischemic heart diseases ( HR = 1.35 , 1.17-1.56), all other forms of heart disease ( HR = 1.51 , 1.21-1.89), primary hypertension and renal disease ( HR = 3.11 , 1.82-5.30), cerebrovascular disease ( HR = 1.64 , 1.37-1.97), other circulatory system diseases ( HR = 1.71 , 1.09-2.69), other chronic lower respiratory diseases ( HR = 1.39 , 1.12-1.73), other chronic liver disease ( HR = 1.89 , 1.06-3.37), renal failure ( HR = 1.91 , 1.33-2.74), motor vehicle accidents ( HR = 1.60 , 1.07-2.37), and all other diseases (HR =1.30, 1.10-1.54), but with lower risk of uterine cancer ( HR = 0.37 , 95% CI: 0.15-0.90) and Alzheimer’s disease ( HR = 0.65 , 95% CI: 0.47-0.92). Conclusion. Hypertension was associated with increased risk of all-cause mortality and 17 out of 67 causes of death, with most of these being circulatory disease outcomes, however, some of the remaining associations are unlikely to be causal. Further studies are needed to clarify associations with less common causes of death and potential causality across outcomes.

Temporal patterns of suicide and circulatory system disease-related mortality are inversely correlated in several countries

Background Nearly 800,000 suicides occur worldwide annually and suicide rates are increasing faster than population growth. Unfortunately, the pathophysiology of suicide remains poorly understood, which has hindered suicide prevention efforts. However, mechanistic clues may be found by studying effects of seasonality on suicide and other mortality causes. Suicides tend to peak in spring-summer periods and nadir in fall-winter periods while circulatory system disease-related mortality tends to exhibit the opposite temporal trends. This study aimed to determine for the first time whether monthly temporal cross-correlations exist between suicide and circulatory system disease-related mortality at the population level. If so and if common biological factors moderate risks for both mortality types, such factors may be discoverable and utilized to improve suicide prevention. Methods We conducted time series analyses of monthly mortality data from northern (England and Wales, South Korea, United States) and southern (Australia, Brazil) hemisphere countries during the period 2009–2018 (N = 41.8 million all-cause mortality cases). We used a Poisson regression variant of the standard cosinor model to determine peak months of mortality. We also estimated cross-correlations between monthly mortality counts from suicide and from circulatory system diseases. Results Suicide and circulatory disease-related mortality temporal patterns were negatively correlated in Australia (− 0.32), Brazil (− 0.57), South Korea (− 0.32), and in the United States (− 0.66), but no temporal correlation was discernable in England and Wales. Conclusions The negative temporal cross-correlations between these mortality types we found in 4 of 5 countries studied suggest that seasonal factors broadly and inversely moderate risks for circulatory disease-related mortality and suicide, but not in all regions, indicating that the effect is not uniform. Since the seasonal factors of temperature and light exert opposite effects on suicide and circulatory disease-related mortality in several countries, we propose that physiologically-adaptive circulatory system responses to heat and light may increase risk for suicide and should be studied to determine whether they affect suicide risk. For example, heat and light increase production and release of the bioactive gas nitric oxide and reduce circulatory system disease by relaxing blood vessel tone, while elevated nitric oxide levels are associated with suicidal behavior, inverse effects that parallel the inverse temporal mortality patterns we detected.

Temporal patterns of suicide and circulatory system disease-related mortality are inversely correlated in several countries

Background Nearly 800,000 suicides occur worldwide annually and suicide rates are increasing faster than population growth. Unfortunately, the pathophysiology of suicide remains poorly understood, which has hindered suicide prevention efforts. However, mechanistic clues may be found by studying effects of seasonality on suicide and other mortality causes. Suicides tend to peak in spring-summer periods and nadir in fall-winter periods while circulatory system disease-related mortality tends to exhibit the opposite temporal trends. This study aimed to determine for the first time whether monthly temporal cross-correlations exist between suicide and circulatory system disease-related mortality at the population level. If so and if common biological factors moderate risks for both mortality types, such factors may be discoverable and utilized to improve suicide prevention.Methods We conducted time series analyses of monthly mortality data from northern (England and Wales, South Korea, United States) and southern (Australia, Brazil) hemisphere countries during the period 2009-2018 (N=41.8 million all-cause mortality cases). We used a Poisson regression variant of the standard cosinor model to determine cross-correlations between monthly mortality rates from suicide and from circulatory system diseases.Results Suicide and circulatory disease-related mortality temporal patterns were negatively correlated in Australia (-0.32), Brazil (-0.57), South Korea (-0.32), and in the United States (-0.66), but no temporal correlation was discernable in England and Wales.Conclusions The negative temporal cross-correlations between these mortality types we found in 4 of 5 countries studied suggest that seasonal factors broadly and inversely moderate risks for circulatory disease-related mortality and suicide. Since the seasonal factors of temperature and light exert opposite effects on suicide and circulatory disease-related mortality in several countries, we propose that physiologically-adaptive circulatory system responses to heat and light may increase risk for suicide and should be studied to determine whether they affect suicide risk. For example, heat and light increase production and release of the bioactive gas nitric oxide and reduce circulatory system disease by relaxing blood vessel tone, while elevated nitric oxide levels are associated with suicidal behavior, inverse effects that parallel the inverse temporal mortality patterns we detected.