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). If older-people's trials are representative, we would expect rates of SAEs in trials to be similar to the rate of hospitalisation and death in the community, and higher than standard trials. Objective: To compare the rate of SAEs in hypertension trials to rates of hospitalisation and death among people taking similar treatments in the community. Study Design: Observational study comparing trial populations to a community cohort. Dataset: We identified trials of Renin-Angiotensin-Aldosterone system (RAAS) drugs for hypertension from clinicatrials.gov. We identified a community comparison population of people with hypertension starting RAAS drugs using primary care data from the Wales, UK (SAIL databank). Population studied: Trial participants from 110 RAAS hypertension trials (11 older-people's trials, mean age 73, and 99 standard trials, mean age 56). Community cohort of people with hypertension (n=56,036, mean age 60) starting RAAS drugs. Outcomes: SAEs in trials (mostly accounted for by hospitalizations or deaths) and all-cause hospitalizations/deaths in the community comparison. SAE rates in older-people and standard trials were compared, adjusting for trial characteristics. The community rate was used to calculate the expected rate of hospitalizations/deaths given the age/sex distribution of each trial. We then compared the expected rate with the observed rate of SAEs in each trial. Results: Older-people's trials had higher SAEs rate than standard trials (0.18 versus 0.11 events/person/year, adjusted IRR 1.74, 95% CI 1.03-2.92). The hospitalisation and death rate in the community for those taking RAAS antihypertensives was much greater than the rate of SAEs reported in standard (ratio 3.70 (3.12-4.55)) and older-people's trials (4.35 (2.56-7.69)), adjusting for age and sex. Conclusion: Trials report substantially fewer SAEs than expected from rates of hospitalisations and deaths among similar-aged people receiving equivalent treatments in the community. SAE rates may be a useful metric to assess trial representativeness. Clinicians should be cautious when applying trial recommendations to older people, even when trials focus on older people.

Do social determinants influence post-stroke aphasia outcomes? A scoping review.

PURPOSE: To conduct a scoping review on five individual social determinants of health (SDOHs): gender, education, ethnicity, socioeconomic status, and social support, in relation to post-stroke aphasia outcomes. MATERIALS AND METHODS: A comprehensive search across five databases was conducted in 2020 and updated in 2022. Twenty-five studies (3363 participants) met the inclusion criteria. Data on SDOHs and aphasia outcomes were extracted and analysed descriptively. RESULTS: Twenty studies provide information on SDOH and aphasia recovery outcomes. Five studies provide insights on SDOH and response to aphasia intervention. Research on SDOH and aphasia recovery has predominantly focussed solely on language outcomes (14 studies), with less research on the role of SDOH on activity, participation, and quality of life outcomes (6 studies). There is no evidence to support a role for gender or education on language outcomes in the first 3 months post stroke. SDOHs may influence aphasia outcomes at or beyond 12 months post onset. CONCLUSIONS: Research on SDOHs and aphasia outcomes is in its infancy. Given SDOHs are modifiable and operate over a lifetime, and aphasia is a chronic condition, there is a pressing need to understand the role of SDOHs on aphasia outcomes in the long term.

Research on the role of Social Determinants of Health (SDoH) and aphasia outcomes is in its infancy.The role of SDoHs has been mainly investigated in relation to language outcomes.Little is known about the SDoHs on activity, participation, and quality of life outcomes.Rehabilitation professionals should consider the potential influence of individual SDoHs such as gender, education, socioeconomic status, ethnicity, and social support on a person's access to aphasia services and aphasia outcomes long term.

Observed and expected serious adverse event rates in randomised clinical trials for hypertension: an observational study comparing trials that do and do not focus on older people.

BACKGROUND: Representativeness of antihypertensive drug trials is uncertain, as many trials recruit few or no older people. Some trials specifically recruit older participants to address this. Here, we assess the representativeness of trials focusing on older people by comparing the rates of serious adverse events in these trials with the rates in trials of a general adult population (ie, standard trials), and comparing these findings to the rate of hospitalisations and deaths in people with hypertension starting a similar treatment in routine clinical practice. METHODS: For this observational study, we identified randomised controlled trials (phase 2/3, 3, or 4) of renin-angiotensin-aldosterone system (RAAS) drugs for hypertension registered from 1999 onwards with ClinicalTrials.gov. Serious adverse events are routinely included in trial reports and are predominantly accounted for by all-cause hospitalisations and deaths. We compared serious adverse event rates in older-people trials (minimum inclusion age ≥60 years) and standard trials (minimum inclusion age <60 years) using Poisson regression models adjusted for trial characteristics (drug type, comparison type, phase, and outcome type). We identified a community cohort of 56 036 adults with hypertension commencing similar drugs to obtain an expected rate of emergency or urgent hospitalisations or deaths, and compared this rate to observed serious adverse event rates in each trial, adjusted for age and sex. For standard trials and for older-people trials, we calculated the standardised ratio of the expected to the observed rate of serious adverse events using Poisson regression models. FINDINGS: We included 110 trials, of which 11 (10%) were older-people trials and 99 (90%) were standard trials. Older-people trials had a higher rate of serious adverse events than did standard trials (median events per person per year 0·18 [IQR 0·12-0·29] vs 0·11 [0·08-0·18]; adjusted incidence rate ratio 1·76 [95% CI 1·01-3·03]). The hospitalisation and death rate in the community for those taking RAAS antihypertensives was much greater than the rate of serious adverse events reported in standard trials (standardised ratio [SR] 4·23, 95% CI 3·51-5·09) and older-people trials (4·76, 2·89-7·86), adjusting for age and sex. The magnitude of risk increase for serious adverse events in community patients taking RAAS did not differ when comparing older-people and standard trials (ratio of SRs 1·13, 95% CI 0·66-1·92). INTERPRETATION: Trials report substantially fewer serious adverse events than expected from rates of hospitalisations and deaths among similar-aged people receiving equivalent treatments in the community. Serious adverse event rates might be a useful metric to assess trial representativeness. Clinicians should be cautious when applying trial recommendations to older people, even when trials focus on older participants. FUNDING: Wellcome Trust, Medical Research Council.