Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland.

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21·3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.

Impact of a Prior Cancer Diagnosis on Quality of Care and Survival Following Acute Myocardial Infarction: Retrospective Population-Based Cohort Study in England.

BACKGROUND: An increasing proportion of patients with cancer experience acute myocardial infarction (AMI). We investigated differences in quality of AMI care and survival between patients with and without previous cancer diagnoses. METHODS: A retrospective cohort study using Virtual Cardio-Oncology Research Initiative data. Patients aged 40+ years hospitalized in England with AMI between January 2010 and March 2018 were assessed, ascertaining previous cancers diagnosed within 15 years. Multivariable regression was used to assess effects of cancer diagnosis, time, stage, and site on international quality indicators and mortality. RESULTS: Of 512 388 patients with AMI (mean age, 69.3 years; 33.5% women), 42 187 (8.2%) had previous cancers. Patients with cancer had significantly lower use of ACE (angiotensin-converting enzyme) inhibitors/angiotensin receptor blockers (mean percentage point decrease [mppd], 2.6% [95% CI, 1.8-3.4]) and lower overall composite care (mppd, 1.2% [95% CI, 0.9-1.6]). Poorer quality indicator attainment was observed in patients with cancer diagnosed in the last year (mppd, 1.4% [95% CI, 1.8-1.0]), with later stage disease (mppd, 2.5% [95% CI, 3.3-1.4]), and with lung cancer (mppd, 2.2% [95% CI, 3.0-1.3]). Twelve-month all-cause survival was 90.5% in noncancer controls and 86.3% in adjusted counterfactual controls. Differences in post-AMI survival were driven by cancer-related deaths. Modeling improving quality indicator attainment to noncancer patient levels showed modest 12-month survival benefits (lung cancer, 0.6%; other cancers, 0.3%). CONCLUSIONS: Measures of quality of AMI care are poorer in patients with cancer, with lower use of secondary prevention medications. Findings are primarily driven by differences in age and comorbidities between cancer and noncancer populations and attenuated after adjustment. The largest impact was observed in recent cancer diagnoses (<1 year) and lung cancer. Further investigation will determine whether differences reflect appropriate management according to cancer prognosis or whether opportunities to improve AMI outcomes in patients with cancer exist.

Acute heart failure presentation, management, and outcomes in cancer patients: a national longitudinal study.

AIMS: Currently, little evidence exists on survival and quality of care in cancer patients presenting with acute heart failure (HF). The aim of the study is to investigate the presentation and outcomes of hospital admission with acute HF in a national cohort of patients with prior cancer. METHODS AND RESULTS: This retrospective, population-based cohort study identified 221 953 patients admitted to a hospital in England for HF during 2012-2018 (12 867 with a breast, prostate, colorectal, or lung cancer diagnosis in the previous 10 years). We examined the impact of cancer on (i) HF presentation and in-hospital mortality, (ii) place of care, (iii) HF medication prescribing, and (iv) post-discharge survival, using propensity score weighting and model-based adjustment. Heart failure presentation was similar between cancer and non-cancer patients. A lower percentage of patients with prior cancer were cared for in a cardiology ward [-2.4% age point difference (ppd) (95% CI -3.3, -1.6)] or were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists (ACEi/ARB) for heart failure with reduced ejection fraction [-2.1 ppd (-3.3, -0.9)] than non-cancer patients. Survival after HF discharge was poor with median survival of 1.6 years in prior cancer and 2.6 years in non-cancer patients. Mortality in prior cancer patients was driven primarily by non-cancer causes (68% of post-discharge deaths). CONCLUSION: Survival in prior cancer patients presenting with acute HF was poor, with a significant proportion due to non-cancer causes of death. Despite this, cardiologists were less likely to manage cancer patients with HF. Cancer patients who develop HF were less likely to be prescribed guideline-based HF medications compared with non-cancer patients. This was particularly driven by patients with a poorer cancer prognosis.

Glycosylated haemoglobin and prognosis in 10,536 people with cancer and pre-existing diabetes: a meta-analysis with dose-response analysis.

AIMS: To assess whether glycaemic control is associated with prognosis in people with cancer and pre-existing diabetes. METHODS: In this pre-registered systematic review (PROSPERO: CRD42020223956), PubMed and Web of Science were searched on 25th Nov 2021 for studies investigating associations between glycosylated haemoglobin (HbA1c) and prognosis in people with diabetes and cancer. Summary relative risks (RRs) and 95% Confidence Intervals (CIs) for associations between poorly controlled HbA1c or per 1-unit HbA1c increment and cancer outcomes were estimated using a random-effects meta-analysis. We also investigated the impact of potential small-study effects using the trim-and-fill method and potential sources of heterogeneity using subgroup analyses. RESULTS: Fifteen eligible observational studies, reporting data on 10,536 patients with cancer and pre-existing diabetes, were included. Random-effects meta-analyses indicated that HbA1c ≥ 7% (53 mmol/mol) was associated with increased risks of: all-cause mortality (14 studies; RR: 1.14 [95% CI: 1.03-1.27]; p-value: 0.012), cancer-specific mortality (5; 1.68 [1.13-2.49]; p-value: 0.011) and cancer recurrence (8; 1.68 [1.18-2.38; p-value: 0.004]), with moderate to high heterogeneity. Dose-response meta-analyses indicated that 1-unit increment of HbA1c (%) was associated with increased risks of all-cause mortality (13 studies; 1.04 [1.01-1.08]; p-value: 0.016) and cancer-specific mortality (4; 1.11 [1.04-1.20]; p-value: 0.003). All RRs were attenuated in trim-and-fill analyses. CONCLUSIONS: Our findings suggested that glycaemic control might be a modifiable risk factor for mortality and cancer recurrence in people with cancer and pre-existing diabetes. High-quality studies with a larger sample size are warranted to confirm these findings due to heterogeneity and potential small-study effects. In the interim, it makes clinical sense to recommend continued optimal glycaemic control.

Risk Factors for Heart Failure: 20-Year Population-Based Trends by Sex, Socioeconomic Status, and Ethnicity.

BACKGROUND: There are multiple risk factors for heart failure, but contemporary temporal trends according to sex, socioeconomic status, and ethnicity are unknown. METHODS: Using a national UK general practice database linked to hospitalizations (1998-2017), 108 638 incident heart failure patients were identified. Differences in risk factors among patient groups adjusted for sociodemographic factors and age-adjusted temporal trends were investigated using logistic and linear regression. RESULTS: Over time, a 5.3 year (95% CI, 5.2-5.5) age difference between men and women remained. Women had higher blood pressure, body mass index, and cholesterol than men (P<0.0001). Ischemic heart disease prevalence increased for all to 2006 before reducing in women by 0.5% per annum, reaching 42.7% (95% CI, 41.7-43.6), but not in men, remaining at 57.7% (95% CI, 56.9-58.6; interaction P=0.002). Diabetes mellitus prevalence increased more in men than in women (interaction P<0.0001). Age between the most deprived (74.6 years [95% CI, 74.1-75.1]) and most affluent (79.9 [95% CI, 79.6-80.2]) diverged (interaction P<0.0001), generating a 5-year gap. The most deprived had significantly higher annual increases in comorbidity numbers (+0.14 versus +0.11), body mass index (+0.14 versus +0.11 kg/m2), and lower smoking reductions (-1.2% versus -1.7%) than the most affluent. Ethnicity trend differences were insignificant, but South Asians were overall 6 years and the black group 9 years younger than whites. South Asians had more ischemic heart disease (+16.5% [95% CI, 14.3-18.6]), hypertension (+12.5% [95% CI, 10.5-14.3]), and diabetes mellitus (+24.3% [95% CI, 22.0-26.6]), and the black group had more hypertension (+12.3% [95% CI, 9.7-14.8]) and diabetes mellitus (+13.1% [95% CI, 10.1-16.0]) but lower ischemic heart disease (-10.6% [95% CI, -13.6 to -7.6]) than the white group. CONCLUSIONS: Population groups show distinct risk factor trend differences, indicating the need for contemporary tailored prevention programs.

Cardiometabolic Polygenic Risk Scores and Osteoarthritis Outcomes: A Mendelian Randomization Study Using Data From the Malmö Diet and Cancer Study and the UK Biobank.

OBJECTIVE: To investigate the causal role of cardiometabolic risk factors in osteoarthritis (OA) using associated genetic variants. METHODS: We studied 27,691 adults from the Malmö Diet and Cancer Study (MDCS) and replicated novel findings among 376,435 adults from the UK Biobank. Trait-specific polygenic risk scores for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, triglyceride levels, body mass index (BMI), fasting plasma glucose (FPG) levels, and systolic blood pressure (BP) were used to test the associations of genetically predicted elevations in each trait with incident OA diagnosis (n = 3,559), OA joint replacement (n = 2,780), or both (total OA; n = 4,226) in Mendelian randomization (MR) analyses in the MDCS, and with self-reported and/or hospital-diagnosed OA (n = 65,213) in the UK Biobank. Multivariable MR, MR-Egger, and weighted median MR were used to adjust for potential pleiotropic biases. RESULTS: In the MDCS, genetically predicted elevation in LDL cholesterol level was associated with a lower risk of OA diagnosis (odds ratio [OR] 0.83 [95% confidence interval (95% CI) 0.73-0.95] per 1SD increase) and total OA (OR 0.87 [95% CI 0.78-0.98]), which was supported by multivariable MR for OA diagnosis (OR 0.84 [95% CI 0.75-0.95]) and total OA (0.87 [95% CI 0.78-0.97]), and by conventional 2-sample MR for OA diagnosis (OR 0.86 [95% CI 0.75-0.98]). MR-Egger indicated no pleiotropic bias. Genetically predicted elevation in BMI was associated with an increased risk of OA diagnosis (OR 1.65 [95% CI 1.14-2.41]), while MR-Egger indicated pleiotropic bias and a larger association with OA diagnosis (OR 3.25 [1.26-8.39]), OA joint replacement (OR 3.81 [95% CI 1.39-10.4]), and total OA (OR 3.41 [95% CI 1.43-8.15]). No associations were observed between genetically predicted HDL cholesterol level, triglyceride level, FPG level, or systolic BP and OA outcomes. The associations with LDL cholesterol levels were replicated in the UK Biobank (OR 0.95 [95% CI 0.93-0.98]). CONCLUSION: Our MR study provides evidence of a causal role of lower LDL cholesterol level and higher BMI in OA.

Conceptualizing multiple drug use in patients with comorbidity and multimorbidity: proposal for standard definitions beyond the term polypharmacy.

With older and aging populations, patients experience multiple chronic diseases at the same time. Individual chronic disease guidelines often recommend pharmacological therapies as a key intervention, resulting in patients being prescribed multiple regular medications for their different diseases. Although the term "polypharmacy" has been applied to the use of multiple medications, there is no consistent definition, and this term is now being used all inclusively. To improve both scientific rigor and optimal patient care, it is crucial that a standard terminology is used, which reclassifies the term "polypharmacy" into distinct phenotypes relating to the index chronic disease, additional conditions to the index (comorbidity), or the experience of multiple chronic conditions at the same time (multimorbidity). Using three exemplar index conditions; heart failure, type 2 diabetes, and breast cancer, we propose the reclassification of the term "polypharmacy" into three distinct phenotypes. First, index drug or multi-index drug therapy, where each index condition creates multiple drug use for that condition; second, codrug therapy, where addition of other comorbid conditions increases the multiple drug use and may influence the management of the index disease and third, multidrug therapy, where adult population with multimorbidity may be on many drugs. This article reviews guidelines for the individual exemplars to develop the basis for the new terms and then develops the pharmacoepidemiology of multiple drug use further by reviewing the evidence on the relationship between the phenotypic classification and important outcomes. The importance of standardizing "polypharmacy" terminology for the scientific agenda and clinical practice is that it relates to an index condition or disease safety outcomes including drug interactions, adverse side effects in hospital admissions, and related "polypill" concept.

Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland.

AIMS: This study was designed to evaluate whether survival rates in patients with heart failure (HF) are better than those in patients with diagnoses of the four most common cancers in men and women, respectively, in a contemporary primary care cohort in the community in Scotland. METHODS AND RESULTS: Data were obtained from the Primary Care Clinical Informatics Unit from a database of 1.75 million people registered with 393 general practices in Scotland. Sex-specific survival modelling was undertaken using Cox proportional hazards models, adjusted for potential confounders. A total of 56 658 subjects were eligible for inclusion in the study. These represented a total of 147 938 person-years of follow-up (median follow-up: 2.04 years). In men, HF (reference group; 5-year survival: 55.8%) had worse mortality outcomes than prostate cancer [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.57-0.65; 5-year survival: 68.3%], and bladder cancer (HR 0.88, 95% CI 0.81-0.96; 5-year survival: 57.3%), but better outcomes than lung cancer (HR 3.86, 95% CI 3.65-4.07; 5-year survival: 8.4%) and colorectal cancer (HR 1.23, 95% CI 1.16-1.31; 5-year survival: 48.9%). In women, HF (reference group; 5-year survival: 49.5%) had worse mortality outcomes than breast cancer (HR 0.55, 95% CI 0.51-0.59; 5-year survival 77.7%), but better outcomes than colorectal cancer (HR 1.21, 95% CI 1.13-1.29; 5-year survival 51.5%), lung cancer (HR 3.82, 95% CI 3.60-4.05; 5-year survival 10.4%), and ovarian cancer (HR 1.98, 95% CI 1.80-2.17; 5-year survival 38.2%). CONCLUSIONS: Despite advances in management, HF remains as 'malignant' as some of the common cancers in both men and women.

"Sometimes we can't fix things": a qualitative study of health care professionals' perceptions of end of life care for patients with heart failure.

BACKGROUND: Although heart failure has a worse prognosis than some cancers, patients often have restricted access to well-developed end of life (EoL) models of care. Studies show that patients with advanced heart failure may have a poor understanding of their condition and its outcome and, therefore, miss opportunities to discuss their wishes for EoL care and preferred place of death. We aimed to explore the perceptions and experiences of health care professionals (HCPs) working with patients with heart failure around EoL care. METHODS: A qualitative in-depth interview study nested in a wider ethnographic study of unplanned admissions in patients with heart failure (HoldFAST). We interviewed 24 HCPs across primary, secondary and community care in three locations in England, UK - the Midlands, South Central and South West. RESULTS: The study revealed three issues impacting on EoL care for heart failure patients. Firstly, HCPs discussed approaches to communicating with patients about death and highlighted the challenges involved. HCPs would like to have conversations with patients and families about death and dying but are aware that patient preferences are not easy to predict. Secondly, professionals acknowledged difficulties recognising when patients have reached the end of their life. Lack of communication between patients and professionals can result in situations where inappropriate treatment takes place at the end of patients' lives. Thirdly, HCPs discussed the struggle to find alternatives to hospital admission for patients at the end of their life. Patients may be hospitalised because of a lack of planning which would enable them to die at home, if they so wished. CONCLUSIONS: The HCPs regarded opportunities for patients with heart failure to have ongoing discussions about their EoL care with clinicians they know as essential. These key professionals can help co-ordinate care and support in the terminal phase of the condition. Links between heart failure teams and specialist palliative care services appear to benefit patients, and further sharing of expertise between teams is recommended. Further research is needed to develop prognostic models to indicate when a transition to palliation is required and to evaluate specialist palliative care services where heart failure patients are included.

Multi-drug therapy in chronic condition multimorbidity: a systematic review.

BACKGROUND: Older populations often suffer from multimorbidity and guidelines for each condition are often associated with recommended drug therapy management. Yet, how different and specific multimorbidity is associated with number and type of multi-drug therapies in general populations is unknown. AIM: The aim of this systematic review was to synthesize the current evidence on patterns of multi-drug prescribing in family practice. METHODS: A systematic review on six common chronic conditions: diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), osteoarthritis and depression was conducted, with a focus on studies which looked at any potential combination of two or more multimorbidity. Studies were identified from searches of MEDLINE, EMBASE, PsychINFO, the Allied and Complementary Medicine Database (AMED) and the Health Management Information Consortium (HMIC) databases from 1960 to 2013. RESULTS: A total of eleven articles were selected based on study criteria. Our review identified very few specific studies which had explicitly investigated the association between multimorbidity and multi-drug therapy. Relevant chronic conditions literature showed nine observational studies and two reviews of comorbid depression drug treatment. Most (seven) of the articles had focused on the chronic condition and comorbid depression and whether antidepressant management had been optimal or not, while four studies focused on other multimorbidities mainly heart failure, COPD and diabetes. CONCLUSIONS: Very few studies have investigated associations between specific multimorbidity and multi-drug therapy, and most currently focus on chronic disease comorbid depression outcomes. Further research needs to identify this area as key priority for older populations who are prescribed high levels of multiple drug therapy.

Chronic condition comorbidity and multidrug therapy in general practice populations: a cross-sectional linkage study.

OBJECTIVES: The study investigated (1) the association between comorbidity and multidrug prescribing compared with the index condition, and (2) the association between vascular comorbidity and non-vascular condition key drug prescribing. DESIGN: Cross-sectional study linking anonymised computer consultations with prescription records for a 2-year time period. SETTING: 11 general practices in North Staffordshire, England. PARTICIPANTS: Study groups aged 40 years and over (N=12 875). Within six conditions, comorbid group with the other five conditions was compared with an 'alone' group without them. Additionally, how the 'vascular' (one of diabetes, cardiovascular disease and cerebrovascular disease) comorbidity influenced chronic obstructive pulmonary disease (COPD), osteoarthritis (OA) or depression drug prescribing was investigated. OUTCOME MEASURES: Based on the British National Formulary, five main drug chapters constituted a measure of drug counts, with low count as 2 or less and high multidrug count as 3 or more. Key drugs prescribed for COPD, OA and depression were derived from guidelines. RESULTS: The adjusted associations between the comorbid groups and higher multidrug count compared with their respective 'alone' group were: odds ratio (OR) 7.1 (95% CI 5.6 to 9.0) for depression, OR 5.4 (95% CI 4.6 to 6.3) for cardiovascular disease, OR 3.7 (95% CI 2.8 to 5.0) for cerebrovascular disease, OR 3.6 (95% CI 3.1 to 4.3) for OA, OR 3.5 (95% CI 3.0 to 4.2) for diabetes and OR 3.2 (95% CI 2.6 to 4.0) for COPD. In COPD, vascular comorbidity was associated with a significant reduction in key COPD drug treatments (adjusted OR 0.6 (95% CI 0.4 to 0.8). In depression, vascular comorbidity was associated with a reduction in key depression drug treatments (OR 0.6 (95% CI 0.4 to 0.7)). CONCLUSIONS: Our findings show that multidrug prescribing for different body systems is higher with comorbidity and may be associated with lower likelihood of prescribing for specific conditions. Further research is required on whether multidrug prescribing influences the outcomes of care for chronic conditions.

Multidrug and optimal heart failure therapy prescribing in older general practice populations: a clinical data linkage study.

OBJECTIVE: To investigate multidrug therapy in the cardiovascular disease (CVD) population and whether it was associated with suboptimal drug prescribing in heart failure (HF). DESIGN: A population-based cross-sectional clinical data linkage study. SETTING: The clinical database populations were registered with three general practices in North Staffordshire that are part of a research network. PARTICIPANTS: 3155 patients aged 50 years and over were selected on the basis of a CVD-related prescription and a CVD consultation code applied to their electronic medical record in a 2-year time period. All available diagnostic data were linked to all drugs prescribed data during this time period. Two study groups were: (1) HF and (2) non-HF CVD (reference group). EXPOSURE: A standard drug formulary system was used to define four multidrug count categories based on the number of different British National Formulary drug chapters prescribed at the same time. PRIMARY AND SECONDARY OUTCOME MEASURES: Optimal HF therapy was defined as the prescribing of ACE inhibitor (ACEi) or a combination of ACEi and ß-blocker in the 2-year time window. An additional three specific CVD drug categories that are indicated in HF were also measured. RESULTS: The HF group, compared with the reference group, had higher non-CVD multidrug therapy (26% with 7 or more counts compared with 14% in the non-HF CVD reference group). For the first-choice optimal drug treatment for HF with ACEi (64%) or ACEi and ß-blocker combined therapy (23%), the multidrug-adjusted associations between the HF group and the reference group were OR 3.89; 95% CI 2.8 to 5.5 and 1.99; 1.4 to 2.9, respectively. These estimates were not influenced by adjustment for sociodemographic factors and multidrug counts. CONCLUSIONS: Multidrug therapy prescribing is much higher in the HF group than in a comparable CVD group but did not influence optimal drug prescribing.

Potential health impacts of multiple drug prescribing for older people: a case-control study.

Using a prescription-survey linkage dataset for 4506 people aged ≥50 years from six general practices, the null hypothesis that multiple drug prescribing was not associated with changes in health over a 3-year time-period was investigated. There was a significant trend in the adjusted association between higher levels of multidrug therapy and deterioration in both physical and psychological health over a 3-year time period. The study highlights the potential need for assessing drug prescribing in terms of overall health.

Transient ischaemic attack in a patient with known temporal arteritis: a case report.

INTRODUCTION: Older populations are more at risk of problems such as temporal arteritis or polymyalgia rheumatica, and these conditions are often first diagnosed in general practice, with usual ongoing care and long-term treatment with oral steroids. These inflammatory conditions are also potential risk factors for other complicating presentations such as transient ischaemic attacks, but the precise comorbid links and how these might influence clinical management in general practice are unclear. CASE PRESENTATION: An 82-year-Caucasian woman living alone requested a home visit after a single episode of speech disturbance and disorientation which lasted 15 minutes. This occurred 2 weeks after cessation of her oral prednisolone for temporal arteritis, which was clinically diagnosed in 2006 and later confirmed by a biopsy. She also had a past medical history of ischaemic heart disease based on symptom presentation and an abnormal ECG in October 2005, but no other relevant risk factors for cardiovascular disease. CONCLUSIONS: Transient ischaemic attack is an alternative presentation or complication of an inflammatory disease such as temporal arteritis. The clinical implications of this case relate to the assessment of comorbid risk in TA and in tailoring the drug treatment. In using prednisolone treatments in such patients, general practitioners will need to carefully titrate drug doses and the duration of treatment to prevent complications. Clear evidence for the precise type of management remains to be established.