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1.
JAMA Intern Med ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491268

RESUMO

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

2.
Eur J Endocrinol ; 185(3): 375-385, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34228632

RESUMO

Objective: To evaluate if subclinical thyroid dysfunction is associated with cardiovascular (CV) risk in patients with atrial fibrillation (AF). Methods: Swiss-AF is a prospective cohort of community-dwelling participants aged ≥ 65 years with AF. Primary outcome was a composite endpoint of CV events (myocardial infarctions, stroke/transitory ischemic events, systemic embolism, heart failure (HF) hospitalizations, CV deaths). Secondary outcomes were component endpoints, total mortality, and AF-progression. Exposures were thyroid dysfunction categories, TSH and fT4. Sensitivity analyses were performed for amiodarone use, thyroid hormones use, and competing events. Results: 2415 patients were included (mean age: 73.2 years; 27% women). 196 (8.4%) had subclinical hypothyroidism and 53 (2.3%) subclinical hyperthyroidism. Subclinical thyroid dysfunction was not associated with CV events, during a median follow-up of 2.1 years (max 5 years): age- and sex-adjusted hazard ratio (adjHR) of 0.99 (95% CI: 0.69-1.41) for subclinical hypothyroidism and 0.55 (95% CI: 0.23-1.32) for subclinical hyperthyroidism. Results remained robust following multivariable adjustment and sensitivity analyses. In euthyroid patients, fT4 levels were associated with an increased risk for the composite endpoint and HF (adjHR: 1.46, 95% CI: 1.04-2.05; adjHR: 1.70, 95% CI: 1.08-2.66, respectively, for the highest quintile vs the middle quintile). Results remained similar following multivariable adjustment and remained significant for HF in sensitivity analyses. No association between subclinical thyroid dysfunction and total mortality or AF-progression was found. Conclusions: Subclinical hypothyroidism was not associated with increased CV risk in AF patients. Higher levels of fT4 with normal TSH were associated with a higher risk for HF.


Assuntos
Fibrilação Atrial/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças da Glândula Tireoide/epidemiologia , Idoso , Fibrilação Atrial/complicações , Doenças Cardiovasculares/complicações , Feminino , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Doenças da Glândula Tireoide/complicações
3.
Age Ageing ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34324628

RESUMO

BACKGROUND: older people remain underrepresented in clinical trials, and evidence generated in younger populations cannot always be generalized to older patients. OBJECTIVE: to identify key barriers and to discuss solutions to specific issues affecting recruitment and retention of older participants in clinical trials based on experience gained from six current European randomised controlled trials (RCTs) focusing on older people. METHODS: a multidisciplinary group of experts including representatives of the six RCTs held two networking conferences and compiled lists of potential barriers and solutions. Every item was subsequently allocated points by each study team according to how important it was perceived to be for their RCTs. RESULTS: the six RCTs enrolled 7,612 older patients. Key barriers to recruitment were impaired health status, comorbidities and diverse health beliefs including priorities within different cultural systems. All trials had to increase the number of recruitment sites. Other measures felt to be effective included the provision of extra time, communication training for the study staff and a re-design of patient information. Key barriers for retention included the presence of severe comorbidities and the occurrence of adverse events. Long study duration, frequent study visits and difficulties accessing the study site were also mentioned. Solutions felt to be effective included spending more time maintaining close contact with the participants, appropriate measures to show appreciation and reimbursement of travel arrangements. CONCLUSION: recruitment and retention of older patients in trials requires special recognition and a targeted approach. Our results provide scientifically-based practical recommendations for optimizing future studies in this population.

4.
BMJ ; 374: n1585, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257088

RESUMO

OBJECTIVE: To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. DESIGN: Cluster randomised controlled trial. SETTING: 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. PARTICIPANTS: 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). INTERVENTION: Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. MAIN OUTCOME MEASURE: Primary outcome was first drug related hospital admission within 12 months. RESULTS: 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). CONCLUSIONS: Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02986425.


Assuntos
Hospitalização/estatística & dados numéricos , Prescrição Inadequada/prevenção & controle , Multimorbidade , Polimedicação , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Europa (Continente) , Humanos , Prescrição Inadequada/efeitos adversos
5.
JAMA Netw Open ; 4(2): e2036645, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566107

RESUMO

Importance: Previous trials on the effect of levothyroxine on depressive symptom scores in patients with subclinical hypothyroidism were limited by small sample sizes (N = 57 to 94) and potential biases. Objective: To assess the effect of levothyroxine on the development of depressive symptoms in older adults with subclinical hypothyroidism in the largest trial on this subject and to update a previous meta-analysis including the results from this study. Design, Setting, and Participants: This predefined ancillary study analyzed data from participants in the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism (TRUST) trial, a double-blind, randomized, placebo-controlled, parallel-group clinical trial conducted from April 2013 to October 31, 2016. The TRUST trial included adults aged 65 years or older diagnosed with subclinical hypothyroidism, defined as the presence of persistently elevated thyroid-stimulating hormone (TSH) levels (4.6-19.9 mIU/L) with free thyroxine (T4) within the reference range. Participants were identified from clinical and general practitioner laboratory databases and recruited from the community in Switzerland, the Netherlands, Ireland, and the UK. This ancillary study included a subgroup of 472 participants from the Netherlands and Switzerland; after exclusions, a total of 427 participants (211 randomized to levothyroxine and 216 to placebo) were analyzed. This analysis was conducted from December 1, 2019, to September 1, 2020. Interventions: Randomization to either levothyroxine or placebo. Main Outcomes and Measures: Depressive symptom scores after 12 months measured with the Geriatric Depression Scale (GDS-15), with higher scores indicating more depressive symptoms (minimal clinically important difference = 2). Results: A total of 427 participants with subclinical hypothyroidism (mean [SD] age, 74.52 [6.29] years; 239 women [56%]) were included in this analysis. The mean (SD) TSH level was 6.57 (2.22) mIU/L at baseline and decreased after 12 months to 3.83 (2.29) mIU/L in the levothyroxine group; in the placebo group, it decreased from 6.55 (2.04) mIU/L to 5.91 (2.66) mIU/L. At baseline, the mean (SD) GDS-15 score was 1.26 (1.85) in the levothyroxine group and 0.96 (1.58) in the placebo group. The mean (SD) GDS-15 score at 12 months was 1.39 (2.13) in the levothyroxine and 1.07 (1.67) in the placebo group with an adjusted between-group difference of 0.15 for levothyroxine vs placebo (95% CI, -0.15 to 0.46; P = .33). In a subgroup analysis including participants with a GDS-15 of at least 2, the adjusted between-group difference was 0.61 (95% CI, -0.32 to 1.53; P = .20). Results did not differ according to age, sex, or TSH levels. A previous meta-analysis (N = 278) on the association of levothyroxine with depressive symptoms was updated to include these findings, resulting in an overall standardized mean difference of 0.09 (95% CI, -0.05 to 0.22). Conclusions and Relevance: This ancillary study of a randomized clinical trial found that depressive symptoms did not differ after levothyroxine therapy compared with placebo after 12 months; thus, these results do not provide evidence in favor of levothyroxine therapy in older persons with subclinical hypothyroidism to reduce the risk of developing depressive symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT01853579.


Assuntos
Doenças Assintomáticas , Depressão/psicologia , Hipotireoidismo/tratamento farmacológico , Tiroxina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/psicologia , Masculino , Tireotropina/sangue , Tiroxina/sangue , Resultado do Tratamento
6.
Hypertension ; 77(2): 662-671, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33356398

RESUMO

The association of blood pressure (BP) and hypertension with the presence of different types of brain lesions in patients with atrial fibrillation is unclear. BP values were obtained in a multicenter cohort of patients with atrial fibrillation. Systolic and diastolic BP was categorized in predefined groups. All patients underwent brain magnetic resonance imaging and neurocognitive testing. Brain lesions were classified as large noncortical or cortical infarcts, small noncortical infarcts, microbleeds, or white matter lesions. White matter lesions were graded according to the Fazekas scale. Overall, 1738 patients with atrial fibrillation were enrolled in this cross-sectional analysis (mean age, 73 years, 73% males). Mean BP was 135/79 mm Hg, and 67% of participants were taking BP-lowering treatment. White matter lesions Fazekas ≥2 were found in 54%, large noncortical or cortical infarcts in 22%, small noncortical infarcts in 21%, and microbleeds in 22% of patients, respectively. Compared with patients with systolic BP <120 mm Hg, the adjusted odds ratios (95% CI) for Fazekas≥2 was 1.25 (0.94-1.66), 1.41 (1.03-1.93), and 2.54 (1.65-3.95) among patients with systolic BP of 120 to 140, 140 to 160, and ≥160 mm Hg (P for linear trend<0.001). Per 5 mm Hg increase in systolic and diastolic BP, the adjusted ß-coefficient (95% CI) for log-transformed white matter lesions was 0.04 (0.02-0.05), P<0.001 and 0.04 (0.01-0.06), P=0.004. Systolic BP was associated with small noncortical infarcts (odds ratios [95% CI] per 5 mm Hg 1.05 [1.01-1.08], P=0.006), microbleeds were associated with hypertension, but large noncortical or cortical infarcts were not associated with BP or hypertension. After multivariable adjustment, BP and hypertension were not associated with neurocognitive function. Among patients with atrial fibrillation, BP is strongly associated with the presence and extent of white matter lesions, but there is no association with large noncortical or cortical infarcts. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.


Assuntos
Fibrilação Atrial/fisiopatologia , Pressão Sanguínea/fisiologia , Infarto Encefálico/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Hipertensão/fisiopatologia , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Infarto Encefálico/complicações , Infarto Encefálico/fisiopatologia , Estudos Transversais , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
7.
Sci Rep ; 10(1): 19111, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154486

RESUMO

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.


Assuntos
Depressão/complicações , Doenças da Glândula Tireoide/complicações , Glândula Tireoide/fisiopatologia , Depressão/fisiopatologia , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/fisiopatologia , Testes de Função Tireóidea
8.
PLoS One ; 15(10): e0240167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035257

RESUMO

BACKGROUND: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is considered as risk factor for the development of mild cognitive impairment (MCI) and dementia. However, dynamics of cognitive functions are subtle, and neurocognitive assessments largely differ in detecting these changes. We aimed to develop and evaluate a score which represents the common aspects of the cognitive functions measured by validated tests (i.e., "general cognitive construct"), while reducing overlap between tests and be more sensitive to identify changes in overall cognitive functioning. METHODS: We developed the CoCo (cognitive construct) score to reflect the cognitive performance obtained by all items of four neurocognitive assessments (Montreal Cognitive Assessment (MoCA); Trail Making Test; Semantic Fluency, animals; Digital Symbol Substitution Test). The sample comprised 2,415 AF patients from the Swiss Atrial Fibrillation Cohort Study (Swiss-AF), 87% aged at least 65 years. Psychometric statistics were calculated for two cognitive measures based on (i) the full set of items from the neurocognitive test battery administered in the Swiss-AF study (i.e., CoCo item set) and (ii) the items from the widely used MoCA test. For the CoCo item set, a factor score was derived based on a principal component analysis, and its measurement properties were analyzed. RESULTS: Both the MoCA item set and the full neurocognitive test battery revealed good psychometric properties, especially the full battery. A one-factor model with good model fit and performance across time and groups was identified and used to generate the CoCo score, reflecting for each patient the common cognitive skill performance measured across the full neurocognitive test battery. The CoCo score showed larger effect sizes compared to the MoCA score in relation to relevant clinical variables. CONCLUSION: The derived factor score allows summarizing AF patients' cognitive performance as a single score. Using this score in the Swiss-AF project increases measurement sensitivity and decreases the number of statistical tests needed, which will be helpful in future studies addressing how AF affects the risk of developing cognitive impairment.


Assuntos
Fibrilação Atrial/complicações , Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos/normas , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Cognição , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Masculino , Psicometria/métodos , Psicometria/normas
9.
Health Qual Life Outcomes ; 18(1): 317, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993637

RESUMO

BACKGROUND: The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy. METHODS: Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person's EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living. RESULTS: 224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon's evenness index score of 0.86) than the EQ-5D-3L (Shannon's evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index. CONCLUSION: Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.


Assuntos
Atividades Cotidianas/psicologia , Multimorbidade , Polimedicação , Qualidade de Vida , Inquéritos e Questionários/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Psicometria/instrumentação , Reprodutibilidade dos Testes
10.
J Am Heart Assoc ; 9(15): e016075, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32750290

RESUMO

Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5-minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal-to-normal intervals, square root of the mean squared differences of successive normal-to-normal intervals and mean heart rate) were calculated. During follow-up, an end point committee adjudicated each cause of death. During a mean follow-up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including ß blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1-2.6; P=0.01) and all-cause death (hazard ratio, 1.42; 95% CI, 1.02-1.98; P=0.04). Conclusions The HRV index measured in a single 5-minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.


Assuntos
Fibrilação Atrial/mortalidade , Doenças Cardiovasculares/mortalidade , Frequência Cardíaca , Idoso , Fibrilação Atrial/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Eletrocardiografia , Eletrocardiografia Ambulatorial , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco
11.
J Am Heart Assoc ; 9(12): e014890, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32529888

RESUMO

Background A cointervention in a randomized clinical trial (RCT) is medical care given in addition to the tested intervention. If cointerventions are unbalanced between trial arms, the results may be biased. We hypothesized that cointerventions would be more adequately reported in RCTs without full blinding or at risk of bias. Methods and Results To describe the reporting of cointerventions and to evaluate the factors associated with their reporting, we did a systematic search of all RCTs evaluating pharmacological interventions on cardiovascular outcomes published in 5 high-impact journals. The reporting of cointerventions, blinding, and risk of bias were extracted and evaluated independently by 2 reviewers (E.M., L.A.). Cointerventions were inadequately reported in 87 of 123 RCTs (70.7%), with 56 (45.5%) providing no information on cointerventions and 31 (25.2%) providing only partial information. Of the RCTs, 52 (42.3%) had inadequate blinding of participants and/or personnel and 63 (51.2%) of the RCTs were judged at risk of bias. In univariable analysis, the reporting of cointerventions was not associated with blinding of participants and/or personnel (odds ratio [OR], 1.04; 95% CI, 0.47-2.27 for adequately versus inadequately blinded trials) or with risk of bias (OR, 1.47; 95% CI, 0.67-3.21 for at low risk of bias versus trials at risk of bias). In multivariable analysis, only a follow-up of <1 month was associated with the adequate reporting of cointerventions (OR, 3.63; 95% CI, 1.21-10.91). Conclusions More than two-thirds of recent major cardiovascular trials did not adequately report cointerventions. The quality of reporting was not better among trials that were not fully blinded or at risk for bias. Registration URL: https://www.crd.york.ac.uk/PROSP​ERO/. Unique identifier: CRD42018106771.


Assuntos
Doenças Cardiovasculares/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Viés , Confiabilidade dos Dados , Humanos , Resultado do Tratamento
12.
Int J Cardiol Heart Vasc ; 29: 100556, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32577496

RESUMO

Aims: Atrial fibrillation (AF) and atrial flutter (AFL) are two of the most common atrial arrhythmias and often coexist. Many patients with AF or AFL are symptomatic, which impacts their quality of life (QoL). The purpose of this study was to determine whether coexistent AFL represents an added burden for AF patients. Methods: We combined baseline data from two large prospective, observational, multicenter cohort studies (BEAT-AF and Swiss-AF). All 3931 patients included in this analysis had documented AF. We obtained information on comorbidities, medication, and lifestyle factors. All participants had a clinical examination and a resting ECG. Symptom burden and QoL at the baseline examination were compared between patients with and without coexistent AFL using multivariable adjusted regression models. Results: Overall, 809 (20.6%) patients had a history of AFL. Patients with coexistent AFL more often had history of heart failure (28% vs 23%, p = 0.01), coronary artery disease (30% vs 26%, p = 0.007), failed therapy with antiarrhythmic drugs (44% vs 29%, p < 0.001), and more often underwent AF-related interventions (36% vs 17%, p < 0.001). They were more often symptomatic (70% vs 66%, p = 0.04) and effort intolerant (OR: 1.14; 95% CI: 1.01-1.28; p = 0.04). Documented AFL on the baseline ECG was associated with more symptoms (OR: 2.30; 95% CI: 1.26-4.20; p = 0.007). Conclusion: Our data indicates that patients with coexistent AF and AFL are more often symptomatic and report poorer quality of life compared to patients suffering from AF only.

13.
J Gerontol A Biol Sci Med Sci ; 75(9): e89-e94, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32577745

RESUMO

BACKGROUND: Fatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue. METHOD: This study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60-19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 µg (25 µg if weight <50 kg or known coronary heart diseases) together with dose adjustments to achieve a normal TSH and mock titration in the placebo group. Main outcome was the change in physical and mental fatigability using the Pittsburgh Fatigability Scale over 1 year, assessed through multivariable linear regression with adjustment for country, sex, and levothyroxine starting dose. RESULTS: Among 230 participants, the mean ± standard deviation (SD) TSH was 6.2 ± 1.9 mIU/L at baseline and decreased to 3.1 ± 1.3 with LT4 (n = 119) versus 5.3 ± 2.3 with placebo (n = 111, p < .001) after 1 year. After adjustment we found no between-group difference at 1 year on perceived physical (0.2; 95% CI -1.8 to 2.1; p = .88), or mental fatigability (-1.0; 95% CI -2.8 to 0.8; p = .26). In participants with higher fatigability at baseline (≥15 points for the physical score [n = 88] or ≥13 points for the mental score [n = 41]), the adjusted between-group differences at 1 year were 0.4 (95% CI -3.6 to 2.8, p = .79) and -2.2 (95% CI -8.8 to 4.5, p = .51). CONCLUSIONS: Levothyroxine in older adults with mild subclinical hypothyroidism provides no change in physical or mental fatigability.


Assuntos
Fadiga/etiologia , Hipotireoidismo/tratamento farmacológico , Tiroxina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Fadiga/tratamento farmacológico , Feminino , Humanos , Hipotireoidismo/complicações , Masculino , Tireotropina/sangue , Tiroxina/sangue
14.
Heart ; 106(23): 1847-1852, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32234819

RESUMO

OBJECTIVE: We aimed to investigate changes in atrial fibrillation (AF)-related symptoms and quality of life (QoL) over time, and their impact on prognosis. METHODS: We prospectively followed 3836 patients with known AF for a mean of 3.7 years. Information on AF-related symptoms and QoL was obtained yearly. The primary end point was a composite of stroke or systemic embolism. Main secondary end points included stroke subtypes, all-cause mortality, cardiovascular death, hospitalisation for congestive heart failure (CHF), myocardial infarction and major bleeding. We assessed associations using multivariable, time-updated Cox proportional hazards models. RESULTS: Mean age was 72 years, 72% were male. Patients with AF-related symptoms (66%) were younger (70 vs 74 years, p<0.0001), more often had paroxysmal AF (56% vs 37%, p<0.0001) and had lower QoL (71 vs 72 points, p=0.009). The incidence of the primary end point was 1.05 and 1.02 per 100 person-years in patients with and without symptoms, respectively. The multivariable adjusted HR (aHR) (95% CIs) for the primary end point was 1.11 (0.77 to 1.59; p=0.56) for AF-related symptoms. AF-related symptoms were not associated with any of the secondary end points. QoL was not significantly related to the primary end point (aHR per 5-point increase 0.98 (0.94 to 1.03; p=0.37)), but was significantly related to CHF hospitalisations (0.92 (0.90 to 0.94; p<0.0001)), cardiovascular death (0.90 (0.86 to 0.95; p<0.0001)) and all-cause mortality (0.88 (0.86 to 0.90; p<0.0001)). CONCLUSIONS: AF-related symptoms were not associated with adverse outcomes and should therefore not be the basis for prognostic treatment decisions. QoL was strongly associated with CHF, cardiovascular death and all-cause mortality.

15.
BMC Health Serv Res ; 20(1): 220, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183810

RESUMO

BACKGROUND: Several approaches to medication optimisation by identifying drug-related problems in older people have been described. Although some interventions have shown reductions in drug-related problems (DRPs), evidence supporting the effectiveness of medication reviews on clinical and economic outcomes is lacking. Application of the STOPP/START (version 2) explicit screening tool for inappropriate prescribing has decreased inappropriate prescribing and significantly reduced adverse drug reactions (ADRs) and associated healthcare costs in older patients with multi-morbidity and polypharmacy. Therefore, application of STOPP/START criteria during a medication review is likely to be beneficial. Incorporation of explicit screening tools into clinical decision support systems (CDSS) has gained traction as a means to improve both quality and efficiency in the rather time-consuming medication review process. Although CDSS can generate more potential inappropriate medication recommendations, some of these have been shown to be less clinically relevant, resulting in alert fatigue. Moreover, explicit tools such as STOPP/START do not cover all relevant DRPs on an individual patient level. The OPERAM study aims to assess the impact of a structured drug review on the quality of pharmacotherapy in older people with multi-morbidity and polypharmacy. The aim of this paper is to describe the structured, multi-component intervention of the OPERAM trial and compare it with the approach in the comparator arm. METHOD: This paper describes a multi-component intervention, integrating interventions that have demonstrated effectiveness in defining DRPs. The intervention involves a structured history-taking of medication (SHiM), a medication review according to the systemic tool to reduce inappropriate prescribing (STRIP) method, assisted by a clinical decision support system (STRIP Assistant, STRIPA) with integrated STOPP/START criteria (version 2), followed by shared decision-making with both patient and attending physician. The developed method integrates patient input, patient data, involvement from other healthcare professionals and CDSS-assistance into one structured intervention. DISCUSSION: The clinical and economical effectiveness of this experimental intervention will be evaluated in a cohort of hospitalised, older patients with multi-morbidity and polypharmacy in the multicentre, randomized controlled OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multi-morbid elderly), which will be completed in the last quarter of 2019. TRIAL REGISTRATION: Universal Trial Number: U1111-1181-9400 Clinicaltrials.gov: NCT02986425, Registered 08 December 2016. FOPH (Swiss national portal): SNCTP000002183. Netherlands Trial Register: NTR6012 (07-10-2016).


Assuntos
Sistemas de Apoio a Decisões Clínicas , Hospitalização , Prescrição Inadequada/prevenção & controle , Reconciliação de Medicamentos/métodos , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Doença Crônica/tratamento farmacológico , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Multimorbidade , Polimedicação , Projetos de Pesquisa
16.
Rev Med Suisse ; 16(684): 455-458, 2020 Mar 04.
Artigo em Francês | MEDLINE | ID: mdl-32134225

RESUMO

Subclinical hypothyroidism is frequent and its treatment by thyroid hormones is debated. Current guidelines tend to recommend a treatment for symptomatic adults or for thyrotropin (TSH) levels > 10 mIU/l. Nevertheless, new evidence from systematic review, -including 21 trials and 2192 participants, demonstrated that thyroid hormone replacement has no clinically relevant benefit on patients' symptoms or prognosis. An international and independent panel -including physicians, methodologists and patients issues a strong recommendation (BMJ Rapid Recommendation) against thyroid hormones therapy for adults with subclinical hypothyroidism. This recommendation does not apply to women who are pregnant or trying to conceive or to patients with TSH > 20 mIU/l.


Assuntos
Hipotireoidismo/tratamento farmacológico , Hormônios Tireóideos/uso terapêutico , Humanos , Hipotireoidismo/sangue , Prognóstico , Tireotropina/sangue
17.
Am J Med ; 133(7): 848-856.e5, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32171774

RESUMO

BACKGROUND: Subclinical hypothyroidism has been associated with heart failure, but only small trials assessed whether treatment with levothyroxine has an impact on cardiac function. METHODS: In a randomized, double-blind, placebo-controlled, trial nested within the TRUST trial, Swiss participants ages ≥65 years with subclinical hypothyroidism (thyroid-stimulating hormone [TSH] 4.60-19.99 mIU/L; free thyroxine level within reference range) were randomized to levothyroxine (starting dose of 50 µg daily) to achieve TSH normalization or placebo. The primary outcomes were the left ventricular ejection fraction for systolic function and the ratio between mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e' ratio) for diastolic function. Secondary outcomes included e' lateral/septal, left atrial volume index, and systolic pulmonary artery pressure. RESULTS: A total of 185 participants (mean age 74.1 years, 47% women) underwent echocardiography at the end of the trial. After a median treatment duration of 18.4 months, the mean TSH decreased from 6.35 mIU/L to 3.55 mIU/L with levothyroxine (n = 96), and it remained elevated at 5.29 mIU/L with placebo (n = 89). The adjusted between-group difference was not significant for the mean left ventricular ejection fraction (62.7% vs 62.5%, difference = 0.4%, 95% confidence interval -1.8% to 2.5%, P = 0.72) and the E/e' ratio (10.6 vs 10.1, difference 0.4, 95% confidence interval -0.7 to 1.4, P = 0.47). No differences were found for the secondary diastolic function parameters or for interaction according to sex, baseline TSH, preexisting heart failure, and treatment duration (P value >0.05). CONCLUSION: Systolic and diastolic heart function did not differ after treatment with levothyroxine compared with placebo in older adults with mild subclinical hypothyroidism.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Hipotireoidismo/tratamento farmacológico , Volume Sistólico/fisiologia , Tiroxina/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Diástole , Relação Dose-Resposta a Droga , Método Duplo-Cego , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/fisiopatologia , Masculino , Prognóstico , Volume Sistólico/efeitos dos fármacos , Sístole , Função Ventricular Esquerda/fisiologia
18.
Eur Heart J Acute Cardiovasc Care ; 9(6): 589-598, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29862825

RESUMO

BACKGROUND: Controversy remains regarding the prevalence of hyperglycaemia in non-diabetic patients hospitalised with acute coronary syndrome and its prognostic value for long-term outcomes. METHODS AND RESULTS: We evaluated the prevalence of hyperglycaemia (defined as fasting glycaemia ⩾10 mmol/l) among patients with no known diabetes at the time of enrolment in the prospective Special Program University Medicine-Acute Coronary Syndromes cohort, as well as its impact on all-cause death, myocardial infarction, stroke and incidence of diabetes at one year. Among 3858 acute coronary syndrome patients enrolled between December 2009-December 2014, 709 (18.4%) had known diabetes, while 112 (3.6%) of non-diabetic patients had hyperglycaemia at admission. Compared with non-hyperglycaemic patients, hyperglycaemic individuals were more likely to present with ST-elevation myocardial infarction and acute heart failure. At discharge, hyperglycaemic patients were more frequently treated with glucose-lowering agents (8.9% vs 0.66%, p<0.001). At one-year, adjudicated all-cause death was significantly higher in non-diabetic patients presenting with hyperglycaemia compared with patients with no hyperglycaemia (5.4% vs 2.2%, p=0.041) and hyperglycaemia was a significant predictor of one-year mortality (adjusted hazard ratio 2.39, 95% confidence interval 1.03-5.56). Among patients with hyperglycaemia, 9.8% had developed diabetes at one-year, while the corresponding proportion among patients without hyperglycaemia was 1.8% (p<0.001). In multivariate analysis, hyperglycaemia at presentation predicted the onset of treated diabetes at one-year (odds ratio 4.15, 95% confidence interval 1.59-10.86; p=0.004). CONCLUSION: Among non-diabetic patients hospitalised with acute coronary syndrome, a fasting hyperglycaemia of ⩾10 mmol/l predicted one-year mortality and was associated with a four-fold increased risk of developing diabetes at one year.


Assuntos
Síndrome Coronariana Aguda/sangue , Glicemia/metabolismo , Jejum/sangue , Hiperglicemia/sangue , Síndrome Coronariana Aguda/complicações , Diabetes Mellitus , Feminino , Seguimentos , Humanos , Hiperglicemia/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
19.
BMJ Open ; 9(7): e029716, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350252

RESUMO

INTRODUCTION: Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association. METHODS AND ANALYSIS: We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal. PROSPERO REGISTRATION NUMBER: CRD42018091627.


Assuntos
Depressão/epidemiologia , Doenças da Glândula Tireoide/epidemiologia , Estudos de Coortes , Humanos , Metanálise como Assunto , Escalas de Graduação Psiquiátrica , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Testes de Função Tireóidea , Hormônios Tireóideos/metabolismo , Tireotropina/metabolismo
20.
BMJ Open ; 9(6): e026769, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31164366

RESUMO

INTRODUCTION: Multimorbidity and polypharmacy are important risk factors for drug-related hospital admissions (DRAs). DRAs are often linked to prescribing problems (overprescribing and underprescribing), as well as non-adherence with drug regimens for different reasons. In this trial, we aim to assess whether a structured medication review compared with standard care can reduce DRAs in multimorbid older patients with polypharmacy. METHODS AND ANALYSIS: OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people is a European multicentre, cluster randomised, controlled trial. Hospitalised patients ≥70 years with ≥3 chronic medical conditions and concurrent use of ≥5 chronic medications are included in the four participating study centres of Bern (Switzerland), Utrecht (The Netherlands), Brussels (Belgium) and Cork (Ireland). Patients treated by the same prescribing physician constitute a cluster, and clusters are randomised 1:1 to either standard care or Systematic Tool to Reduce Inappropriate Prescribing (STRIP) intervention with the help of a clinical decision support system, the STRIP Assistant. STRIP is a structured method performing customised medication reviews, based on Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment criteria to detect potentially inappropriate prescribing. The primary endpoint is any DRA where the main reason or a contributory reason for the patient's admission is caused by overtreatment or undertreatment, and/or inappropriate treatment. Secondary endpoints include number of any hospitalisations, all-cause mortality, number of falls, quality of life, degree of polypharmacy, activities of daily living, patient's drug compliance, the number of significant drug-drug interactions, drug overuse and underuse and potentially inappropriate medication. ETHICS AND DISSEMINATION: The local Ethics Committees in Switzerland, Ireland, The Netherlands and Belgium approved this trial protocol. We will publish the results of this trial in a peer-reviewed journal. MAIN FUNDING: European Union's Horizon 2020 programme. TRIAL REGISTRATION NUMBER: NCT02986425 , SNCTP000002183 , NTR6012, U1111-1181-9400.


Assuntos
Doença Crônica/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Geriatria , Hospitalização/estatística & dados numéricos , Prescrição Inadequada/prevenção & controle , Lista de Medicamentos Potencialmente Inapropriados/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/tratamento farmacológico , Análise por Conglomerados , Sistemas de Apoio a Decisões Clínicas , Feminino , Humanos , Masculino , Multimorbidade , Polimedicação , Qualidade de Vida
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