Characteristics of Randomized Controlled Trials Designed for Elderly: A Systematic Review

Objectives To quantify the proportion of randomized controlled trials (RCTs) specifically designed for elderly, and to assess their characteristics, as compared to RCTs not specifically designed for elderly. Design Review and synthesis of published literature. Measurements We searched PubMed for articles published in the year 2012. We included RCTs. Articles were excluded if not conducted with human subjects or if findings of secondary analyses were reported. A random sample of 10% was drawn and of this selection the following trial characteristics were extracted: sample size, disease category, age of sample, and age-related inclusion criteria. Clinical trials were defined to be specifically designed for elderly if a lower age cut-off of ≥ 55 years was used, or when participants had an average age of ≥ 70 years. Results The search strategy yielded 26,740 articles, from which a random sample was drawn, resulting in 2375 articles. After exclusion, data was extracted from 1369 publications. Of these 1369 RCTs, 96 (7%) were specifically designed for elderly. In comparison with trials not designed for older adults, trials designed for elderly contained a significantly larger median number of participants (125 vs. 80, p = 0.008) significantly more trials designed for elderly fell into the disease categories eye (6% vs. 2%, p = 0.005), musculoskeletal (13% vs. 7%, p = 0.023) and circulatory system (16% vs. 9%, p = 0.039). No significant difference was observed with regard to the other disease categories. Conclusion There is a low proportion of RCTs specifically designed for elderly. As older patients will increasingly form the majority in medical practice, there is an urgent need for stronger evidence for the formulation of treatment guidelines specifically for older adults.


International variation in GP treatment strategies for subclinical hypothyroidism in older adults: a case-based survey

Background: There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people.

Aim: To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics.

Design and setting: Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand.

Method: The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L).

Results: A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]).

Conclusion: GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care.


Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study

Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (>70 years).

Design Prospective cohort study.

Setting PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands.

Participants 5461 participants, mean age 75.3 years, who were at risk of cardiovascular disease. Blood pressure was measured every three months during an average of 3.2 years. Visit-to-visit variability in blood pressure was defined as the standard deviation of blood pressure measurements between visits.

Main outcome measures Four domains of cognitive function, testing selective attention, processing speed, and immediate and delayed memory. In a magnetic resonance imaging substudy of 553 participants, structural brain volumes, cerebral microbleeds, infarcts, and white matter hyperintensities were measured.

Results Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests: attention (mean difference high versus low thirds) 3.08 seconds (95% confidence interval 0.85 to 5.31), processing speed −1.16 digits coded (95% confidence interval −1.69 to −0.63), immediate memory −0.27 pictures remembered (95% confidence interval −0.41 to −0.13), and delayed memory −0.30 pictures remembered (95% confidence interval −0.49 to −0.11). Furthermore, higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infarcts, and higher variability in diastolic blood pressure was associated with cerebral microbleeds (all P<0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors. Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age.