Multimorbidity clusters and their associations with health-related quality of life in two UK cohorts.

Background: Identifying clusters of multiple long-term conditions (MLTCs), also known as multimorbidity, and their associated burden may facilitate the development of effective and cost-effective targeted healthcare strategies. This study aimed to identify clusters of MLTCs and their associations with long-term health-related quality of life (HRQoL) in two UK population-based cohorts.

Methods: Age-stratified clusters of MLTCs were identified at baseline in UK Biobank (n = 502,363, 54.

A scoping review of the measurement and analysis of frailty in randomised controlled trials.

Background: Frailty is of increasing interest in trials, either as a target of intervention, as an outcome or as a potential treatment modifier. However, frailty measurement is often highly variable. This scoping review assessed how frailty is quantified in randomised controlled trials (RCTs), in what context and for what purposes.

A Cross-Sectional Survey of Fixed-Dose Combination Antihypertensive Medicine Prescribing in Twenty-Four Countries, Including Qualitative Insights.

Background: Treatment inertia, non-adherence and non-persistence to medical treatment contribute to poor blood pressure (BP) control worldwide. Fixed dose combination (FDC) antihypertensive medicines simplify prescribing patterns and improve adherence. The aim of this study was to identify factors associated with prescribing FDC antihypertensive medicines and to understand if these factors differ among doctors worldwide.

Retrospective analysis of carcinogenicity assessments within FDA-notified GRAS determinations.

Frameworks have been developed to standardize the assessment of carcinogenic potential in the pharmaceutical and agrochemical industries, building upon decades of research. Carcinogenicity is also evaluated during the safety evaluation of food substances, using a comprehensive approach unique to each substance. To better understand these approaches, a retrospective assessment was conducted on the publicly available database of substances notified to the United States Food and Drug Administration (US FDA) as being Generally Recognized As Safe (GRAS).

Savings from the introduction of BPaL and BPaLM regimens at the country level.

Background: In 2022, the WHO recommended the 6-month regimens BPaL (bedaquiline + pretomanid + linezolid) and BPaLM (BPaL + moxifloxacin) as treatment options for most forms of drug-resistant TB. SLASH-TB estimates the cost-saving and cost-effectiveness for the healthcare system and patients when a country switches from current standard-of-care treatment regimens to BPaL/BPaLM.

Methodology: Country data from national TB programmes (NTP) are used to calculate the costs for all regimens and treatment outcomes.

Frailty and socioeconomic position: A systematic review of observational studies.

Background: Frailty, an age-related state of reduced physiological reserve, is often associated with lower socio-economic position (SEP). This systematic review synthesised observational studies assessing (i) the association between SEP and frailty prevalence; (ii) how changes in frailty status over time vary by SEP; and (iii) whether the association between frailty and clinical outcomes is modified by SEP.

Methods: We searched three electronic databases from 2001 to 2023.

Description of subgroup reporting in clinical trials of chronic diseases: a meta-epidemiological study.

Introduction: In trials, subgroup analyses are used to examine whether treatment effects differ by important patient characteristics. However, which subgroups are most commonly reported has not been comprehensively described.

Design And Settings: Using a set of trials identified from the US clinical trials register (ClinicalTrials.

Participant characteristics and exclusion from phase 3/4 industry funded trials of chronic medical conditions: meta-analysis of individual participant level data.

Objectives: To assess whether age, sex, comorbidity count, and race and ethnic group are associated with the likelihood of trial participants not being enrolled in a trial for any reason (ie, screen failure).

Design: Bayesian meta-analysis of individual participant level data.

Setting: Industry funded phase 3/4 trials of chronic medical conditions.

Detecting and managing the patient with chronic kidney disease in primary care: A review of the latest guidelines.

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes.

An observational analysis of frailty in combination with loneliness or social isolation and their association with socioeconomic deprivation, hospitalisation and mortality among UK Biobank participants.

Frailty, social isolation, and loneliness have individually been associated with adverse health outcomes. This study examines how frailty in combination with loneliness or social isolation is associated with socioeconomic deprivation and with all-cause mortality and hospitalisation rate in a middle-aged and older population. Baseline data from 461,047 UK Biobank participants (aged 37-73) were used to assess frailty (frailty phenotype), social isolation, and loneliness.

Sex differences in cancer outcomes across the range of eGFR.

Background: People with chronic kidney disease (CKD) have increased incidence and mortality of most cancer types. We hypothesized that the odds of presenting with advanced cancer may vary according to differences in estimated glomerular filtration rate (eGFR), that this could contribute to increased all-cause mortality and that sex differences may exist.

Methods: Data were from Secure Anonymised Information Linkage Databank, including people with de novo cancer diagnosis (2011-17) and two kidney function tests within 2 years prior to diagnosis to determine baseline eGFR (mL/min/1.

The relationship between frailty and social vulnerability: a systematic review.

Both frailty (reduced physiological reserve) and social vulnerability (scarcity of adequate social connections, support, or interaction) become more common as people age and are associated with adverse consequences. Analyses of the relationships between these constructs can be limited by the wide range of measures used to assess them. In this systematic review, we synthesised 130 observational studies assessing the association between frailty and social vulnerability, the bidirectional longitudinal relationships between constructs, and their joint associations with adverse health outcomes.

Multimorbidity and Blood Pressure Control in Patients Attending Primary Care in Canada.

Background: There has been conflicting evidence on the association between multimorbidity and blood pressure (BP) control. This study aimed to investigate this associations in people with hypertension attending primary care in Canada, and to assess whether individual long-term conditions are associated with BP control.

Methods: This was a cross-sectional study in people with hypertension attending primary care in Toronto between January 1, 2017 and December 31, 2019.

Correlations between comorbidities in trials and the community: An individual-level participant data meta-analysis.

Background: People with comorbidities are under-represented in randomised controlled trials, and it is unknown whether patterns of comorbidity are similar in trials and the community.

Methods: Individual-level participant data were obtained for 83 clinical trials (54,688 participants) for 16 index conditions from two trial repositories: Yale University Open Data Access (YODA) and the Centre for Global Clinical Research Data (Vivli). Community data (860,177 individuals) were extracted from the Secure Anonymised Information Linkage (SAIL) databank for the same index conditions.

Personalised lung cancer risk stratification and lung cancer screening: do general practice electronic medical records have a role?

Background: In the United Kingdom (UK), cancer screening invitations are based on general practice (GP) registrations. We hypothesize that GP electronic medical records (EMR) can be utilised to calculate a lung cancer risk score with good accuracy/clinical utility.

Methods: The development cohort was Secure Anonymised Information Linkage-SAIL (2.

Recent developments in frailty identification, management, risk factors and prevention: A narrative review of leading journals in geriatrics and gerontology.

Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention.

Frailty in people with rheumatoid arthritis: a systematic review of observational studies.

Frailty, an age-related decline in physiological reserve, is an increasingly important concept in the management of chronic diseases. The implications of frailty in people with rheumatoid arthritis are not well understood. We undertook a systematic review to assess prevalence of frailty in people with rheumatoid arthritis, and the relationship between frailty and disease activity or clinical outcomes.

Frailty in randomised controlled trials for dementia or mild cognitive impairment measured via the frailty index: prevalence and prediction of serious adverse events and attrition.

Background: Frailty and dementia have a bidirectional relationship. However, frailty is rarely reported in clinical trials for dementia and mild cognitive impairment (MCI) which limits assessment of trial applicability. This study aimed to use a frailty index (FI)-a cumulative deficit model of frailty-to measure frailty using individual participant data (IPD) from clinical trials for MCI and dementia.

Treatment effect modification due to comorbidity: Individual participant data meta-analyses of 120 randomised controlled trials.

Background: People with comorbidities are underrepresented in clinical trials. Empirical estimates of treatment effect modification by comorbidity are lacking, leading to uncertainty in treatment recommendations. We aimed to produce estimates of treatment effect modification by comorbidity using individual participant data (IPD).

Assessing Representativeness of Randomised Controlled Trials using Serious Adverse Events.

Context: The applicability of randomised controlled trials of pharmacological agents to older people with frailty/multimorbidity is often uncertain, due to concerns that trials are not representative. However, assessing trial representativeness is challenging and complex. Objectives: We explore an approach assessing trial representativeness by comparing rates of trial Serious Adverse Events (SAEs: most of which reflect hospitalisations/deaths) to rates of hospitalisation/death in routine care (which, in a trial setting, would be SAEs be definition).

Representativeness of antihypertensive trials: analysis of serious adverse events.

Context: Representativeness of 'standard' antihypertensive drug trials is uncertain, with limited recruitment of older people. Some trials specifically recruit older participants to address this. Trials are obliged to report hospitalizations and deaths, regardless of cause, as Serious Adverse Events (SAEs).

Effect of age, sex, and morbidity count on trial attrition: meta-analysis of individual participant level data from phase 3/4 industry funded clinical trials.

Objectives: To estimate the association between individual participant characteristics and attrition from randomised controlled trials.

Design: Meta-analysis of individual participant level data (IPD).

Data Sources: Clinical trial repositories (Clinical Study Data Request and Yale University Open Data Access).

Multimorbidity and frailty in middle-aged adults with type 2 diabetes mellitus.

Context: Frailty and multimorbidity are common in type 2 diabetes, including in middle-aged people (<65 years). Clinical guidelines recommend adjustment of treatment targets in people with frailty or multimorbidity. However, guidelines do not specify how frailty/multimorbidity should be identified.