Clinical medication reviews (CMRs) are increasingly performed in older persons with multimorbidity and polypharmacy to reduce drug-related problems (DRPs). However, there is limited evidence that a ...CMR can improve clinical outcomes. Little attention has been paid to patients' preferences and needs. The aim of this study was to investigate the effect of a patient-centred CMR, focused on personal goals, on health-related quality of life (HR-QoL), and on number of health problems.
This study was a randomised controlled trial (RCT) performed in 35 community pharmacies and cooperating general practices in the Netherlands. Community-dwelling older persons (≥70 years) with polypharmacy (≥7 long-term medications) were randomly assigned to usual care or to receive a CMR. Randomisation was performed at the patient level per pharmacy using block randomisation. The primary outcomes were HR-QoL (assessed with EuroQol EQ-5D-5L and EQ-Visual Analogue Scale VAS) and number of health problems (such as pain or dizziness), after 3 and 6 months. Health problems were measured with a self-developed written questionnaire as the total number of health problems and number of health problems with a moderate to severe impact on daily life. Between April 2016 and February 2017, we recruited 629 participants (54% females, median age 79 years) and randomly assigned them to receive the intervention (n = 315) or usual care (n = 314). Over 6 months, in the intervention group, HR-QoL measured with EQ-VAS increased by 3.4 points (95% confidence interval CI 0.94 to 5.8; p = 0.006), and the number of health problems with impact on daily life decreased by 12% (difference at 6 months -0.34; 95% CI -0.62 to -0.044; p = 0.024) as compared with the control group. There was no significant difference between the intervention group and control group for HR-QoL measured with EQ-5D-5L (difference at 6 months = -0.0022; 95% CI -0.024 to 0.020; p = 0.85) or total number of health problems (difference at 6 months = -0.30; 95% CI -0.64 to 0.054; p = 0.099). The main study limitations include the risk of bias due to the lack of blinding and difficulties in demonstrating which part of this complex intervention (for example, goal setting, extra attention to patients, reducing health problems, drug changes) contributed to the effects that we observed.
In this study, we observed that a CMR focused on personal goals improved older patients' lives and wellbeing by increasing quality of life measured with EQ-VAS and decreasing the number of health problems with impact on daily life, although it did not significantly affect quality of life measured with the EQ-5D. Including the patient's personal goals and preferences in a medication review may help to establish these effects on outcomes that are relevant to older patients' lives.
Netherlands Trial Register; NTR5713.
The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition.
We ...conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points).
The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval CI, -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest.
Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).
Data on the association between subclinical thyroid dysfunction and coronary heart disease (CHD) and mortality are conflicting.
To summarize prospective evidence about the relationship between ...subclinical thyroid dysfunction and CHD and mortality.
MEDLINE (1950 to January 2008) without language restrictions and reference lists of retrieved articles were searched.
Two reviewers screened and selected cohort studies that measured thyroid function and then followed persons prospectively to assess CHD or mortality.
By using a standardized protocol and forms, 2 reviewers independently abstracted and assessed studies.
Ten of 12 identified studies involved population-based cohorts that included 14 449 participants. All 10 population-based cohort studies examined risks associated with subclinical hypothyroidism (2134 CHD events and 2822 deaths), whereas only 5 examined risks associated with subclinical hyperthyroidism (1392 CHD events and 1993 deaths). In a random-effects model, the relative risk (RR) for subclinical hypothyroidism for CHD was 1.20 (95% CI, 0.97 to 1.49; P for heterogeneity = 0.14; I(2 )= 33.4%). Risk estimates were lower when higher-quality studies were pooled (RR, 1.02 to 1.08) and were higher among participants younger than 65 years (RR, 1.51 CI, 1.09 to 2.09 for studies with mean participant age <65 years and 1.05 CI, 0.90 to 1.22 for studies with mean participant age > or =65 years). The RR was 1.18 (CI, 0.98 to 1.42) for cardiovascular mortality and 1.12 (CI, 0.99 to 1.26) for total mortality. For subclinical hyperthyroidism, the RR was 1.21 (CI, 0.88 to 1.68) for CHD, 1.19 (CI, 0.81 to 1.76) for cardiovascular mortality, and 1.12 (CI, 0.89 to 1.42) for total mortality (P for heterogeneity >0.50; I(2 )= 0% for all studies).
Individual studies adjusted for different potential confounders, and 1 study provided only unadjusted data. Publication bias or selective reporting of outcomes could not be excluded.
Subclinical hypothyroidism and hyperthyroidism may be associated with a modest increased risk for CHD and mortality, with lower risk estimates when pooling higher-quality studies and larger CIs for subclinical hyperthyroidism.
Context:
Although both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are ...conflicting.
Objective:
This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts.
Data Sources:
We searched in MEDLINE and EMBASE from inception until November 2014.
Study Selection:
Two physicians identified prospective cohorts that assessed thyroid function and cognitive outcomes (dementia; Mini-Mental State Examination MMSE).
Data Extraction:
Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. The primary outcome was dementia and decline in cognitive function was the secondary outcome.
Data Synthesis:
Eleven prospective cohorts followed 16,805 participants during a median followup of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (SHyper) (n = 6410), six in subclinical hypothyroidism (SHypo) (n = 7401). Five studies analyzed MMSE decline in SHyper (n = 7895), seven in SHypo (n = 8960). In random-effects models, the pooled adjusted risk ratio for dementia in SHyper was 1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval, 0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant heterogeneity (I2 = 0.0%). The pooled mean MMSE decline from baseline to followup (mean 32 mo) did not significantly differ between SHyper or SHypo vs euthyroidism.
Conclusions:
SHyper might be associated with an elevated risk for dementia, whereas SHypo is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed.
This meta-analysis determined the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction and found a possible association for subclinical hyperthyroidism and dementia.
Multimorbidity and polypharmacy are current challenges when caring for the older population. Both have led to an increase of potentially inappropriate medication (PIM), illustrating the need to ...assess patients' attitudes towards deprescribing. We aimed to assess the prevalence of PIM use and whether this was associated with patient factors and willingness to deprescribe.
We analysed data from the LESS Study, a cross-sectional study on self-reported medication and on barriers and enablers towards the willingness to deprescribe (rPATD questionnaire). The survey was conducted among multimorbid (≥3 chronic conditions) participants ≥70 years with polypharmacy (≥5 long-term medications). A subset of the Beers 2019 criteria was applied for the assessment of medication appropriateness.
Data from 300 patients were analysed. The mean age was 79.1 years (SD 5.7). 53% had at least one PIM (men: 47.8%%, women: 60.4%%; p = 0.007). A higher number of medications was associated with PIM use (p = 0.002). We found high willingness to deprescribe in both participants with and without PIM. Willingness to deprescribe was not associated with PIM use (p = 0.25), nor number of PIMs (p = 0.81).
The willingness of older adults with polypharmacy towards deprescribing was not associated with PIM use in this study. These results suggest that patients may not be aware if they are taking PIMs. This implies the need for raising patients' awareness about PIMs through education, especially in females, in order to implement deprescribing in daily practice.
Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk ...of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.
We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.
Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4;
for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.
In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.
Multimorbidity and polypharmacy are very common in older adults in primary care. Ideally, general practitioners (GPs), should regularly review medication lists to identify inappropriate medication(s) ...and, where appropriate, deprescribe. However, it remains challenging to deprescribe given time constraints and few recommendations from guidelines. Further, patient related barriers and enablers to deprescribing have to be accounted for. The aim of this study was to identify barriers and enablers to deprescribing as reported by older adults with polypharmacy and multimorbidity.
We conducted a survey among participants aged ≥70 years, with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 chronic medications). We invited Swiss GPs, to recruit eligible patients who then completed a paper-based survey on demographics, medications and chronic conditions. We used the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire and added twelve additional Likert scale questions and two open-ended questions to assess barriers and enablers towards deprescribing, which we coded and categorized into meaningful themes.
Sixty four Swiss GPs consented to recruit 5-6 patients each and returned 300 participant responses. Participants were 79.1 years (SD 5.7), 47% female, 34% lived alone, and 86% managed their medications themselves. Sixty-seven percent of participants took 5-9 regular medicines and 24% took ≥10 medicines. The majority of participants (77%) were willing to deprescribe one or more of their medicines if their doctor said it was possible. There was no association with sex, age or the number of medicines and willingness to deprescribe. After adjustment for baseline characteristics, there was a strong positive association between willingness to deprescribe and saying that because they have a good relationship with their GP, they would feel that deprescribing was safe OR 11.3 (95% CI: 4.64-27.3) and agreeing that they would be willing to deprescribe if new studies showed an avoidable risk OR 8.0 (95% CI 3.79-16.9). From the open questions, the most mentioned barriers towards deprescribing were patients feeling well on their current medicines and being convinced that they need all their medicines.
Most older adults with polypharmacy are willing to deprescribe. GPs may be able to increase deprescribing by building trust with their patients and communicating evidence about the risks of medication use.
Objective:
The objective was to determine the risk of stroke associated with subclinical hypothyroidism.
Data Sources and Study Selection:
Published prospective cohort studies were identified through ...a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45–4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5–19.9 mIU/L with normal T4 levels.
Data Extraction and Synthesis:
We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972–2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval CI, 0.91–1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80–1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25–8.80) for individuals aged 18–49 years. There was an increased risk of fatal stroke in the age groups 18–49 and 50–64 years, with a HR of 4.22 (95% CI, 1.08–16.55) and 2.86 (95% CI, 1.31–6.26), respectively (p trend 0.04). We found no increased risk for those 65–79 years old (HR, 1.00; 95% CI, 0.86–1.18) or ≥80 years old (HR, 1.31; 95% CI, 0.79–2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations.
Conclusions:
Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.
Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated ...yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death.
Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated.
Participants of PROSPER had 1.65-fold (95%CI 1.11-2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46-2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36-1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57-3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00-1.20, P-value = 0.044).
Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality.
Context:
Subclinical thyroid dysfunction is common in older people. However, its clinical importance is uncertain.
Objective:
Our objective was to determine the extent to which subclinical ...hyperthyroidism and hypothyroidism influence the risk of heart failure and cardiovascular diseases in older people.
Setting and Design:
The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) is an prospective cohort study.
Patients:
Patients included men and women aged 70–82 yr (n = 5316) with known cardiovascular risk factors or previous cardiovascular disease.
Main Outcome Measures:
Incidence rate of heart failure hospitalization, atrial fibrillation, and cardiovascular events and mortality according to baseline thyroid status were evaluated. Euthyroid participants (TSH =0.45–4.5 mIU/liter) were compared with those with subclinical hyperthyroidism (TSH <0.45 mIU/liter) and those with subclinical hypothyroidism (TSH ≥4.5 mIU/liter, both with normal free T4).
Results:
Subclinical hyperthyroidism was present in 71 participants and subclinical hypothyroidism in 199 participants. Over 3.2 yr follow-up, the rate of heart failure was higher for subclinical hyperthyroidism compared with euthyroidism age- and sex-adjusted hazard ratio (HR) = 2.93, 95% confidence interval (CI) = 1.37–6.24, P = 0.005; multivariate-adjusted HR = 3.27, 95% CI = 1.52–7.02, P = 0.002). Subclinical hypothyroidism (only at threshold >10 mIU/liter) was associated with heart failure (age- and sex-adjusted HR = 3.01, 95% CI = 1.12–8.11, P = 0.029; multivariate HR = 2.28, 95% CI = 0.84–6.23). There were no strong evidence of an association between subclinical thyroid dysfunction and cardiovascular events or mortality, except in those with TSH below 0.1 or over 10 mIU/liter and not taking pravastatin.
Conclusion:
Older people at high cardiovascular risk with low or very high TSH along with normal free T4 appear at increased risk of incident heart failure.
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