Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over.

BACKGROUND: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. METHODS: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure. DISCUSSION: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date. TRIAL REGISTRATION: Nederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).

Validation of the Care-Related Quality of Life Instrument in different study settings: findings from The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS).

PURPOSE: Validity is a contextual aspect of a scale which may differ across sample populations and study protocols. The objective of our study was to validate the Care-Related Quality of Life Instrument (CarerQol) across two different study design features, sampling framework (general population vs. different care settings) and survey mode (interview vs. written questionnaire). METHODS: Data were extracted from The Older Persons and Informal Caregivers Minimum DataSet (TOPICS-MDS, www.topics-mds.eu ), a pooled public-access data set with information on >3,000 informal caregivers throughout the Netherlands. Meta-correlations and linear mixed models between the CarerQol's seven dimensions (CarerQol-7D) and caregiver's level of happiness (CarerQol-VAS) and self-rated burden (SRB) were performed. RESULTS: The CarerQol-7D dimensions were correlated to the CarerQol-VAS and SRB in the pooled data set and the subgroups. The strength of correlations between CarerQol-7D dimensions and SRB was weaker among caregivers who were interviewed versus those who completed a written questionnaire. The directionality of associations between the CarerQol-VAS, SRB and the CarerQol-7D dimensions in the multivariate model supported the construct validity of the CarerQol in the pooled population. Significant interaction terms were observed in several dimensions of the CarerQol-7D across sampling frame and survey mode, suggesting meaningful differences in reporting levels. CONCLUSIONS: Although good scientific practice emphasises the importance of re-evaluating instrument properties in individual research studies, our findings support the validity and applicability of the CarerQol instrument in a variety of settings. Due to minor differential reporting, pooling CarerQol data collected using mixed administration modes should be interpreted with caution; for TOPICS-MDS, meta-analytic techniques may be warranted.

Anaemia in older persons.

Anaemia is common in older individuals and, because of its association with various negative outcomes, adequate diagnosis and treatment is important. The present review focuses on prominent factors included in diagnostic and therapeutic algorithms for anaemia. Although pernicious anaemia is associated with severe vitamin B12 deficiency, evidence of an association between subnormal vitamin B12 and anaemia in older persons in the general population is limited and inconclusive. Accumulating evidence suggests that clinicians should at least reconsider the risks of a low vitamin B12 level before starting vitamin B12 supplementation in older individuals. Although clinicians may be reluctant to measure ferritin in older individuals due to its acute phase properties, such measurements are important in older persons with anaemia, especially in those with signs of inflammation. While a severe age-related decline in renal function may lead to a blunted erythropoietin response and anaemia, elevated erythropoietin levels are associated with increased mortality. More studies are needed to identify the clinical relevance and therapeutic implications of low and high erythropoietin levels in older persons. In contrast to other age-related diseases, telomere length is not associated with anaemia in older individuals in the general population. In conclusion, many issues regarding the aetiology of anaemia in old age remain unresolved. Because current guidelines on anaemia are based on the classic notions of the aetiology of anaemia, they may need to be revised for the highest age groups.

Incidence and predictive factors of lower respiratory tract infections among the very elderly in the general population. The Leiden 85-plus Study.

OBJECTIVES: To target preventive strategies in old age, which of the very elderly are predisposed to developing lower respiratory tract infections was investigated. DESIGN: Prospective observational follow-up study. SETTING: General population. PARTICIPANTS: Unselected cohort of 587 participants aged 85 years in Leiden, The Netherlands. MEASUREMENTS: As reported in the literature, predictive factors were selected and assessed at baseline. During a 5 year follow-up period, information on the development of lower respiratory tract infections was obtained from general practitioners or nursing home physicians. Associations between predictive factors were analysed with Cox regression, and population attributable risks were calculated. RESULTS: The incidence of lower respiratory tract infections among persons aged 85-90 years was 94 (95% CI 80-108) per 1000 person years. After multivariate analysis, history of chronic obstructive pulmonary disease (COPD), smoking, oral glucocorticosteroid use, severe cognitive impairment, history of stroke and declined functional status remained independently associated with the occurrence of lower respiratory tract infections. Smoking was the greatest contributor with a population attributable risk of 32%. CONCLUSION: In the very old, smoking, COPD, stroke and declined functional status were associated with the occurrence of lower respiratory tract infections and provide a means of targeting patients at risk of severe health complications.

Long-term use of proton pump inhibitors and vitamin B12 status in elderly individuals.

BACKGROUND: Some studies have shown that short-term use of proton pump inhibitors decreases the absorption of vitamin B12, but the results of studies into long-term proton pump inhibitor use and vitamin B12 deficiency are inconsistent. AIM: To investigate whether long-term proton pump inhibitor use is associated with an abnormal vitamin B12 status in elderly individuals. METHODS: One hundred and twenty-five long-term (>3, years) proton pump inhibitor users aged 65, years and above were recruited from general practices. Their 125 partners (who did not use proton pump inhibitors) served as the reference group. Vitamin B12 status was determined by serum levels of vitamin B12 and homocysteine, and mean corpuscular volume. RESULTS: No differences in mean vitamin B12 levels were observed between the long-term proton pump inhibitor users and their partners [345 (s.d. 126), pm vs. 339 (s.d. 133), pm, P, =, 0.73], even after adjustment for age, gender, Helicobacter pylori status and C-reactive protein levels (P, =, 0.87). Four proton pump inhibitor users and three partners had vitamin B12 levels <150, pm (3% vs. 2%, P, =, 1.00). No differences between the groups were observed in homocysteine levels and mean corpuscular volume. CONCLUSIONS: No association between long-term proton pump inhibitor use and vitamin B12 status was observed. Regular testing for low vitamin B12 levels in elderly patients on long-term treatment with proton pump inhibitors is therefore not recommended.