Respiratory-related death in individuals with incident asthma and COPD: a competing risk analysis

Background Distinguishing between mortality attributed to respiratory causes and other causes among people with asthma, COPD, and asthma-COPD overlap (ACO) is important. This study used electronic health records in England to estimate excess risk of death from respiratory-related causes after accounting for other causes of death. Methods We used linked Clinical Practice Research Datalink (CPRD) primary care and Office for National Statistics mortality data to identify adults with asthma and COPD from 2005 to 2015. Causes of death were ascertained using death certificates. Hazard ratios (HR) and excess risk of death were estimated using Fine-Gray competing risk models and adjusting for age, sex, smoking status, body mass index and socioeconomic status. Results 65,021 people with asthma and 45,649 with COPD in the CPRD dataset were frequency matched 5:1 with people without the disease on age, sex and general practice. Only 14 in 100,000 people with asthma are predicted to experience a respiratory-related death up to 10 years post-diagnosis, whereas in COPD this is 98 in 100,000. Asthma is associated with an 0.01% excess incidence of respiratory related mortality whereas COPD is associated with an 0.07% excess. Among people with asthma-COPD overlap (N = 22,145) we observed an increased risk of respiratory-related death compared to those with asthma alone (HR = 1.30; 95% CI 1.21–1.40) but not COPD alone (HR = 0.89; 95% CI 0.83–0.94). Conclusions Asthma and COPD are associated with an increased risk of respiratory-related death after accounting for other causes; however, diagnosis of COPD carries a much higher probability. ACO is associated with a lower risk compared to COPD alone but higher risk compared to asthma alone.

Association between cardiometabolic disease multimorbidity and all-cause mortality in 2 million women and men registered in UK general practices

Background Myocardial infarction (MI), stroke and diabetes share underlying risk factors and commonalities in clinical management. We examined if their combined impact on mortality is proportional, amplified or less than the expected risk separately of each disease and whether the excess risk is explained by their associated comorbidities. Methods Using large-scale electronic health records, we identified 2,007,731 eligible patients (51% women) and registered with general practices in the UK and extracted clinical information including diagnosis of myocardial infarction (MI), stroke, diabetes and 53 other long-term conditions before 2005 (study baseline). We used Cox regression to determine the risk of all-cause mortality with age as the underlying time variable and tested for excess risk due to interaction between cardiometabolic conditions. Results At baseline, the mean age was 51 years, and 7% (N = 145,910) have had a cardiometabolic condition. After a 7-year mean follow-up, 146,994 died. The sex-adjusted hazard ratios (HR) (95% confidence interval [CI]) of all-cause mortality by baseline disease status, compared to those without cardiometabolic disease, were MI = 1.51 (1.49–1.52), diabetes = 1.52 (1.51–1.53), stroke = 1.84 (1.82–1.86), MI and diabetes = 2.14 (2.11–2.17), MI and stroke = 2.35 (2.30–2.39), diabetes and stroke = 2.53 (2.50–2.57) and all three = 3.22 (3.15–3.30). Adjusting for other concurrent comorbidities attenuated these estimates, including the risk associated with having all three conditions (HR = 1.81 [95% CI 1.74–1.89]). Excess risks due to interaction between cardiometabolic conditions, particularly when all three conditions were present, were not significantly greater than expected from the individual disease effects. Conclusion Myocardial infarction, stroke and diabetes were associated with excess mortality, without evidence of any amplification of risk in people with all three diseases. The presence of other comorbidities substantially contributed to the excess mortality risks associated with cardiometabolic disease multimorbidity.

Residual Stroke Risk in Atrial Fibrillation

AF contributes to increased stroke risk via various mechanisms, including deranged blood constituents, vessel wall abnormalities and abnormal blood flow. This excess risk is frequently managed with anticoagulation therapy, aimed at preventing thromboembolic complications. Yet, a significant proportion of patients with AF remain at high residual stroke risk despite receiving appropriate dose-adjusted anticoagulation. This article explores the residual stroke risk in AF and potential therapeutic options for these patients.

Using self-controlled case series to understand the relationship between conflict and cholera in Nigeria and the Democratic Republic of Congo

Background Cholera outbreaks contribute significantly to diarrhoeal disease mortality, especially in low-income countries. Cholera outbreaks have several social and environmental risk factors and extreme conditions can act as catalysts for outbreaks. A social extreme with known links to infectious disease outbreaks is conflict, causing disruption to services, loss of income and displacement. Methods Here, we explored this relationship in Nigeria and the Democratic Republic of Congo (DRC), by fitting publicly available cholera and conflict data to conditional logistic regression models. We used the self-controlled case series method in a novel application, to understand if an exposure period of excess risk (conflict), increased the relative incidence of cholera. We also used a sensitivity analysis to understand potential lag effects. Results We found that conflict and cholera had a strong positive relationship, especially in the first week after the event, at a national and sub-national level. Conflict increased the risk of cholera in Nigeria by 3.6 times and 2.6 times for the DRC. Conflict was attributed to 19.7% and 12.3% of cholera outbreaks in Nigeria and the DRC, respectively. This was higher for some states/provinces, with a maximum increased risk of 7.5 times. Conclusion The results found that several states/provinces with the strongest positive relationship were also areas of high reported conflict or were neighbouring states/provinces, suggesting a possible spill-over effect. Our results help highlight the importance of rapid and sufficient assistance during social extremes and the need for pre-existing vulnerabilities such as poverty and access to healthcare to be addressed. In fragile states, conflict resolution should be a top priority to avoid excess risk for both cholera and other health and social implications. Funding Natural Environmental Research Council, UK Medical Research Council, and the Department for International Development.

Acute urinary retention and risk of cancer: population based Danish cohort study

Objective To examine the risk of urogenital, colorectal, and neurological cancers after a first diagnosis of acute urinary retention. Design Nationwide population based cohort study. Setting All hospitals in Denmark. Participants 75 983 patients aged 50 years or older with a first hospital admission for acute urinary retention during 1995-2017. Main outcome measures Absolute risk of urogenital, colorectal, and neurological cancer and excess risk of these cancers among patients with acute urinary retention compared with the general population. Results The absolute risk of prostate cancer after a first diagnosis of acute urinary retention was 5.1% (n=3198) at three months, 6.7% (n=4233) at one year, and 8.5% (n=5217) at five years. Within three months of follow-up, 218 excess cases of prostate cancer per 1000 person years were detected. An additional 21 excess cases per 1000 person years were detected during three to less than 12 months of follow-up, but beyond 12 months the excess risk was negligible. Within three months of follow-up the excess risk for urinary tract cancer was 56 per 1000 person years, for genital cancer in women was 24 per 1000 person years, for colorectal cancer was 12 per 1000 person years, and for neurological cancer was 2 per 1000 person years. For most of the studied cancers, the excess risk was confined to within three months of follow-up, but the risk of prostate and urinary tract cancer remained increased during three to less than 12 months of follow-up. In women, an excess risk of invasive bladder cancer persisted for several years. Conclusions Acute urinary retention might be a clinical marker for occult urogenital, colorectal, and neurological cancers. Occult cancer should possibly be considered in patients aged 50 years or older presenting with acute urinary retention and no obvious underlying cause.

Excess risk and clusters of symptoms after COVID-19 in a large Norwegian cohort

Physical, psychological and cognitive symptoms have been reported as post-acute sequelae for COVID-19 patients but are also common in the general, uninfected population. We aimed to calculate the excess risk and identify patterns of 22 symptoms up to 12 months after COVID-19 infection. We followed more than 70,000 participants in an ongoing cohort study, the Norwegian Mother, Father and Child Cohort Study (MoBa) during the COVID-19 pandemic. Infected and non-infected cohort participants registered presence of 22 different symptoms in March 2021. One year after the initial infection, 13 of 22 symptoms were associated with SARS-CoV-2 infection, based on relative risks between infected and uninfected subjects. For instance, 17.4% of SARS-CoV-2 infected cohort participants reported fatigue that persist 12 months after infection, compared to new occurrence of fatigue that had lasted less than 12 months in 3.8% of non-infected subjects (excess risk 13.6%). The adjusted relative risk for fatigue was 4.8 (95 % CI 3.5 to 6.7). Two main underlying factors explained 50% of the variance in the 13 symptoms. Brain fog, poor memory, dizziness, heart palpitations, and fatigue had high loadings on the first factor, while shortness-of breath and cough had high loadings on the second factor. Lack of taste and smell showed low to moderate correlation to other symptoms. Anxiety, depression and mood swings were not strongly related to COVID-19. Our results suggest that there are clusters of symptoms after COVID-19 due to different mechanisms and question whether it is meaningful to describe long COVID as one syndrome.