This study aims: (1) to describe the pattern and extent of multimorbidity and polypharmacy in UK Biobank participants with chronic obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are associated with increased risk of adverse drug reactions (ADRs) resulting from polypharmacy.Cross-sectional.Community cohort.UK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494 323).Multimorbidity (≥4 conditions) and polypharmacy (≥5 medications) in participants with COPD versus those without. Risk of ADRs (taking ≥3 medications associated with falls, constipation, urinary retention, central nervous system (CNS) depression, bleeding or renal injury) in relation to the presence of COPD and individual comorbidities.Multimorbidity was more common in participants with COPD than those without (17% vs 4%). Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD). Adjusting for age, sex and socioeconomic status, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95% CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to 6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular disease was associated with the greatest risk of taking ≥3 medications associated with falls/renal injury. Concomitant mental health conditions were most strongly associated with medications linked with CNS depression/urinary retention/bleeding.Multimorbidity is common in COPD and associated with high levels of polypharmacy. Co-prescription of drugs with various ADRs is common. Future research should examine the effects on healthcare outcomes of co-prescribing multiple drugs with similar potential ADRs. Clinical guidelines should emphasise assessment of multimorbidity and ADR risk.
The authors studied the joint effect of blood pressure ( BP ) and depression on the risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35,537 patients with coronary heart disease, diabetes, or stroke underwent depression screening and BP measurement recorded concurrently. The authors used Cox's proportional hazards to calculate risk of major adverse cardiovascular event ( MACE ; myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with baseline BP and depression. A total of 11% (3939) had experienced a MACE within 4 years. Patients with very high systolic BP (160–240 mm Hg; hazard ratio, 1.28) and depression (hazard ratio, 1.22) at baseline had significantly higher adjusted risk. Depression had a significant interaction with systolic BP in risk prediction ( P =.03). Patients with a combination of high systolic BP and depression at baseline had 83% higher adjusted risk of MACE , as compared with patients with reference systolic BP without depression. Patients with cardiometabolic disease and comorbid depression may benefit from closer monitoring of systolic BP .
Abstract BACKGROUND AND AIMS The new race-free estimated glomerular filtration rate (eGFR) was developed in 2021. Recently in the UK in keeping with similar initiatives elsewhere, the kidney failure risk equation (KFRE) to predict the risk of kidney failure has been incorporated into clinical guidelines. Referral from primary care to a specialist renal clinic is recommended if eGFR falls to < 30 mL/min/1.73 m2 and/or if the 5-year KFRE is greater than 5%. We investigate the impact of using the race-free eGFR equation and KFRE on CKD diagnosis in primary care and potential referrals to the renal clinic. METHOD Primary care records for 79% of the population of Wales (UK) are held in the electronic health records repository Secure Anonymised Information Linkage Databank (SAIL). We studied serum creatinine values and urine albumin-creatinine ratios (uACRs) from 1 January 2013 to 31 December 2020. We calculated eGFR values using three equations: MDRD, CKD-EPI 2009 and (race-free) CKD-EPI 2021. Using the different equations, we compared the numbers of patients with incident eGFR <60 mL/min/1.73 m2 and incident eGFR < 30 mL/min/1.73 m2 (i.e. their eGFR fell from above to below these values for more than 3 months). For each year from 2013 to 2020, we identified the patients with prevalent eGFR 30–60 mL/min/1.73 m2 those with annual uACR testing and those who met referral criteria by A) eGFR decline and B) KFRE without eGFR decline. RESULTS There were 121 471 patients with prevalent CKD between 2013 and 2020. eGFR values were lowest using the MDRD equation (median 47.1 mL/min/1.73 m2 IQI 39.7–51.9) and highest with the CKD-EPI 2021 equation (median 50.0 mL/min/1.73 m2 IQI 41.6–55.3). Changing between these two equations would have led to a 17.6% reduction in incident eGFR < 60 mL/min/1.73 m2 and a 7.5% reduction in incident eGFR < 30 between 2013 and 2020 (Figure 1). The rate of annual uACR testing fell from 46.3% in 2013 to 25.3% in 2019 (Figure 2). eGFR and uACR testing were reduced further in 2020 during the COVID-19 pandemic. Patients without diabetes and older patients were the least likely to have had uACR testing at any time: for example, amongst those aged 60–70 years, 90.0% of those with diabetes had uACR testing at any time compared to 42.7% of those without diabetes; amongst those aged over 80 years, 79.1% of those with diabetes were tested compared to 32.7% of those without diabetes. In 2019 (the last year before the COVID-19 pandemic), 787/61 721 (1.3%) patients with CKD stage 3 met referral criteria by eGFR decline and an additional 587 (1.0%) by KFRE without eGFR decline. CONCLUSION Using the race-free eGFR equation will reduce diagnoses of incident eGFR < 30 warranting referral to specialist renal clinics. KFRE can be used to identify a significant number of patients at heightened risk of kidney failure, and these numbers may be higher if more uACR testing was performed. Annual uACR testing rates are low, especially in those without diabetes and in older adults. eGFR and uACR testing were markedly reduced during the COVID-19 pandemic in 2020 as most routine disease monitoring stopped. Expanding uACR testing in primary care (particularly in those without diabetes and in older adults) and using KFRE may improve the identification of individuals at risk of progressive kidney disease, but this is challenging during the COVID-19 pandemic.
Abstract Objectives To investigate mortality rates and associated factors, and avoidable mortality, in children/young people with intellectual disabilities. Design Retrospective cohort; individual record-linked data between Scotland’s 2011 Census to 9.5 years of National Records for Scotland death certification data. Setting General community. Participants Children and young people with intellectual disabilities living in Scotland aged 5-24 years, and an age matched comparison group. Main outcome measures Deaths up to 2020: age of death, age-standardised mortality ratios (age-SMRs); causes of death including cause-specific age-SMRs/sex-SMRs; and avoidable deaths. Results Death occurred in 260/ 7,247 (3.6%) children/young people with intellectual disabilities (crude mortality rate=388/100,000 person years), and 528/156,439 (0.3%) children/young people without intellectual disabilities (crude mortality rate=36/100,000 person years). SMR for children/young people with, versus those without, intellectual disabilities were 10.7 for all causes (95% confidence interval (CI)=9.47-12.1), 5.17 for avoidable death (CI=4.19-6.37), 2.3 for preventable death (1.6-3.2), and 16.1 for treatable death (CI=12.5-20.8). SMRs were highest for children (27.4, CI=20.6-36.3) aged 5-9 years, and lowest for young people (6.6, CI=5.1-8.6) aged 20-24 years. SMRs were higher in more affluent neighbourhoods. Crude mortality incidences were higher for the children/young people with intellectual disabilities for most ICD-10 chapters. The most common underlying avoidable causes of mortality for children/young people with intellectual disabilities were epilepsy, aspiration/reflux/choking and respiratory infection, and for children/young people without intellectual disabilities, were suicide, accidental drug-related deaths and car accidents. Conclusion Children with intellectual disabilities had significantly higher rates of all cause, avoidable, treatable, and preventable mortality than their peers. The largest differences were for treatable mortality, particularly at ages 5-9 years. Interventions to improve health-care to reduce treatable mortality should be a priority for children/young people with intellectual disabilities. Examples include improved epilepsy management and risk assessments, and co-ordinated multi-disciplinary actions to reduce aspiration/reflux/choking and respiratory infection. This is necessary across all neighbourhoods. Strengths and limitations of this study Novel use of Census records and record linkage to death records to study mortality in a total population cohort of children and young people with intellectual disabilities. Due to the use of a whole country population, these results are well-powered and generalisable. Despite comprising a whole country population, our study was not large enough to delineate cause-specific mortality ratios by sex. This study was limited by lack of demographic and clinical diagnostic information, including the severity or cause of intellectual disabilities. Reliance on death certificate data is limited by inconsistencies in reporting of cause of death.
It is now well recognised that the risk of severe COVID-19 increases with some long-term conditions (LTCs). However, prior research primarily focuses on individual LTCs and there is a lack of data on the influence of multimorbidity (≥2 LTCs) on the risk of COVID-19. Given the high prevalence of multimorbidity, more detailed understanding of the associations with multimorbidity and COVID-19 would improve risk stratification and help protect those most vulnerable to severe COVID-19. Here we examine the relationships between multimorbidity, polypharmacy (a proxy of multimorbidity), and COVID-19; and how these differ by sociodemographic, lifestyle, and physiological prognostic factors.We studied data from UK Biobank (428,199 participants; aged 37-73; recruited 2006-2010) on self-reported LTCs, medications, sociodemographic, lifestyle, and physiological measures which were linked to COVID-19 test data. Poisson regression models examined risk of COVID-19 by multimorbidity/polypharmacy and effect modification by COVID-19 prognostic factors (age/sex/ethnicity/socioeconomic status/smoking/physical activity/BMI/systolic blood pressure/renal function). 4,498 (1.05%) participants were tested; 1,324 (0.31%) tested positive for COVID-19. Compared with no LTCs, relative risk (RR) of COVID-19 in those with 1 LTC was no higher (RR 1.12 (CI 0.96-1.30)), whereas those with ≥2 LTCs had 48% higher risk; RR 1.48 (1.28-1.71). Compared with no cardiometabolic LTCs, having 1 and ≥2 cardiometabolic LTCs had a higher risk of COVID-19; RR 1.28 (1.12-1.46) and 1.77 (1.46-2.15), respectively. Polypharmacy was associated with a dose response higher risk of COVID-19. All prognostic factors were associated with a higher risk of COVID-19 infection in multimorbidity; being non-white, most socioeconomically deprived, BMI ≥40 kg/m2, and reduced renal function were associated with the highest risk of COVID-19 infection: RR 2.81 (2.09-3.78); 2.79 (2.00-3.90); 2.66 (1.88-3.76); 2.13 (1.46-3.12), respectively. No multiplicative interaction between multimorbidity and prognostic factors was identified. Important limitations include the low proportion of UK Biobank participants with COVID-19 test data (1.05%) and UK Biobank participants being more affluent, healthier and less ethnically diverse than the general population.Increasing multimorbidity, especially cardiometabolic multimorbidity, and polypharmacy are associated with a higher risk of developing COVID-19. Those with multimorbidity and additional factors, such as non-white ethnicity, are at heightened risk of COVID-19.
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Rheumatoid arthritis (RA) is associated with many long-term conditions (LTCs). An understanding of patterns of comorbidity may promote better care of patients with RA.
Objective:
To examine how individuals with other LTCs in rheumatoid arthritis cluster and describe how clusters associate with adverse health outcomes.
Study design:
Longitudinal cohort study.
Dataset:
UK Biobank.
Population studied:
UK Biobank participants aged between 40 and 70 years old who reported RA (n=5,625).
Outcome measure:
Primary outcome measures were risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over a 11-year follow-up.
Results:
A total of 2,566 (46%) participants reported ≥2 other LTCs. This involved 1,138 distinct combinations of LTCs of which 86% (984) were reported by no more than 2 individuals. The most common combination was hypertension with painful conditions (n=117, 4.6%). Latent class analysis created 5 clusters of participants with RA and ≥2 LTCs. For some clusters, one disease was dominant, and in others the most prevalent comorbidities were related. The most common group (38% of participants) centred around hypertension in combination with diabetes and CHD. The next prominent group (20%) involved asthma, COPD and CHD, but also displayed an increased prevalence of diabetes and osteoarthritis. Cancer and thyroid disorders were single dominant conditions in separate groups (11.2% and 13.8% respectively). Lastly, we observed a grouping of patients (16.7%) who reported a collection of functional somatic conditions in which the prevalence of painful conditions, dyspepsia, migraine, IBS, depression, anxiety and diverticular disease were all raised. All derived groups displayed a raised risk of adverse health outcomes, however, three groups showed a higher risk. These comprised the cancer grouping, the grouping with a high prevalence of asthma, COPD, and CHD, and the group centred around hypertension, diabetes, and CHD. In contrast, the participants in the group characterised by painful conditions, dyspepsia and migraine had overall risks similar to that of participants who reported only one LTC.
Conclusions:
An increased risk of adverse health outcome among participants with RA is associated with both type of LTC as well as the overall number of LTCs they experience. These results are relevant for the monitoring and management of patients with RA and multimorbidity.
(From introduction) Diarrhoea remains one of the leading causes of childhood morbidity and mortality in India. Over 450,000 children (0-6 years: ~158,000; 6+ years: ~296,000) were estimated to have died from diarrhoea in India in 2001. The morbidity and mortality associated with diarrhoeal disease is tightly linked with it causing and exacerbating malnutrition; which is particularly problematic in India where over 30% of children are undernourished. Further to this, diarrhoeal disease is also associated with decreased cognitive function in children, thus having serious implications for a child’s future development... (continued in paper)
Background: HIV infection is associated with increased risk of Cardiovascular Diseases (CVD) and risk calculators underpredict these outcomes in infected individuals. The underlying mechanisms leading to high CVD risk are not yet clear. Low-grade inflammation and platelet abnormalities which persist even after individuals undergo successful antiretroviral therapy have been implicated in the development of CVDs in individuals with HIV infection. Objective: This study evaluated plasma levels of platelet activation and inflammation markers in HIV uninfected, HIV infected subjects receiving Anti-retroviral Therapy (ART) and those naive to ART. Materials and Methods: A total of 284 adults comprising of subjects receiving ART (187), ART naive (32) attending an HIV treatment center and HIV uninfected blood donors (65) were investigated in this analytical cross sectional study. Platelet activation and inflammation markers were assessed by measuring plasma levels of sP-selectin, platelet factor 4 (PF4), IL-6 and tumor necrosis factor alpha (TNF-α). Results: HIV infected patients had higher levels of sP- selectin, PF4 and IL-6 than uninfected controls (p<0.001). ART naive subjects had higher levels of PF4 as compared to the individuals receiving ART (p<0.001). Levels of TNF-α did not differ across groups by HIV (p=0.992) or ART status (p=0 993). A positive correlation was observed between IL-6 and sP-selectin levels in HIV infection (r=0.2690; p=0.001) but lacked in the HIV uninfected (r=-0.1065; p=0.5825). Conclusion: Levels of platelet activation and inflammation markers were elevated in HIV infected individuals regardless of ART and significance of this in HIV- related cardiovascular risk should be investigated further.
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