Long-term trajectories of densely reported depressive symptoms during an extended period of the COVID-19 pandemic in Switzerland: Social worries matter.

Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context.

Antipsychotic prescribing and drug-related readmissions in multimorbid older inpatients: a post-hoc analysis of the OPERAM population.

BACKGROUND: Limited data are available on characteristics associated with antipsychotic use in multimorbid older adults. AIM: Primary: to identify patient characteristics associated with antipsychotic prescribing in a multimorbid population of older inpatients with polypharmacy. Secondary: (1) to observe if antipsychotics use during an index hospitalisation was associated with a drug related admission (DRA) within one year, and (2) to describe these cases of antipsychotic-related readmissions. METHOD: This was a secondary analysis of the OPERAM randomized controlled trial. Multivariate analysis assessed the association between characteristics and comorbidities with antipsychotic use. An expert team assessed DRA occurring during the one-year follow-up. RESULTS: Antipsychotics were prescribed to 5.5% (n = 110) patients upon admission while 7.7% (n = 154) inpatients received antipsychotics at any time (i.e. upon admission, during hospitalisation, and/or at discharge). The most frequently prescribed antipsychotics were quetiapine (n = 152), haloperidol (n = 48) and risperidone (n = 22). Antipsychotic prescribing was associated with dementia (OR = 3.7 95%CI[2.2;6.2]), psychosis (OR = 26.2 [7.4;92.8]), delirium (OR = 6.4 [3.8;10.8]), mood disorders (OR = 2.6 [1.6;4.1]),  ≥ 15 drugs a day (OR = 1.7 [1.1;2.6]), functional dependency (Activities of Daily Living score < 50/100) (OR = 3.9 [2.5;6.1]) and < 2 units of alcohol per week (OR = 2.2 [1.4;3.6]). DRA occurred in 458 patients (22.8%) within one year. Antipsychotic prescribing at any time was not associated with DRA (OR = 1.0 [0.3;3.9]) however contributed to 8 DRAs, including 3 falls. CONCLUSION: In this European multimorbid polymedicated older inpatients, antipsychotics were infrequently prescribed, most often at low dosage. Besides neuro-psychiatric symptoms, risk factors for inhospital antipsychotic prescribing were lower functional status and polymedication.

Hospital physicians' and older patients' agreement with individualised STOPP/START-based medication optimisation recommendations in a clinical trial setting.

OBJECTIVE: To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. METHODS: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. RESULTS: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9-14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30-50 ml/min/1.73 m2; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients' reluctance to discontinue or initiate medication. CONCLUSION: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations. CLINICAL TRIAL REGISTRATION: Trial Registration Number NCT02986425.

Trends and regional variation in vertebroplasty and kyphoplasty in Switzerland: a population-based small area analysis.

Regional variation in procedure use often reflects the uncertainty about the risks and benefit of procedures. In Switzerland, regional variation in vertebroplasty and balloon kyphoplasty rates was high, although the variation declined between 2013 and 2018. Substantial parts of the variation remained unexplained, and likely signal unequal access and differing physician opinion. PURPOSE: To assess trends and regional variation in percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) use across Switzerland. METHODS: We conducted a population-based analysis using patient discharge data from all Swiss acute care hospitals for 2013-2018. We calculated age/sex-standardized mean procedure rates and measures of variation across VP/BKP-specific hospital areas (HSAs). We assessed the influence of potential determinants of variation using multilevel regression models with incremental adjustment for demographics, cultural/socioeconomic, health, and supply factors. RESULTS: We analyzed 7855 discharges with VP/BKP from 31 HSAs. The mean age/sex-standardized procedure rate increased from 16 to 20/100,000 persons from 2013 to 2018. While the variation in procedure rates across HSAs declined, the overall variation remained high (systematic component of variation from 56.8 to 6.9 from 2013 to 2018). Determinants explained 52% of the variation. CONCLUSIONS: VP/BKP procedure rates increased and regional variation across Switzerland declined but remained at a high level. A substantial part of the regional variation remained unexplained by potential determinants of variation.

Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

Prognostic significance of present atrial fibrillation on a single office electrocardiogram in patients with atrial fibrillation.

BACKGROUND: Evidence for the association of atrial fibrillation (AF) present on the ECG and cardiovascular outcomes in AF patients is limited. OBJECTIVE: To investigate the prognostic significance of AF on a single surface ECG for cardiovascular outcomes in AF patients. METHODS: A total of 3642 AF patients were prospectively enrolled. Main exclusion criteria were rhythms other than sinus rhythm (SR) or AF. The primary end-point was a composite of all-cause death and hospitalizations for congestive heart failure (CHF). Secondary end-points were all-cause death, CHF hospitalizations, cardiovascular death, myocardial infarction, any stroke and stroke subtypes. Associations were assessed with multivariable Cox proportional hazards models. RESULTS: Mean age was 71 years, 28% were female, and mean follow-up was 3.4 years. Patients with SR on the ECG at study enrolment (56%) were younger (69 vs. 74 years, P < 0.0001), had more often paroxysmal AF (73 vs. 18%, P < 0.0001) and fewer comorbidities. The incidence of the primary end-point was 1.8 and 3.1 per 100 person-years in patients with SR and AF, respectively. The multivariable-adjusted hazard ratio was 1.4 (95% confidence intervals 1.1; 1.7; P = 0.001) for patients with AF on the ECG compared to patients with SR. The hazard ratios (95% confidence intervals) were 1.4 (1.1; 1.8; P = 0.006) for all-cause death, 1.5 (1.2; 1.9; P = 0.001) for CHF and 1.6 (1.1; 2.2; P = 0.006) for cardiovascular death. None of the other associations were statistically significant. CONCLUSIONS: The presence of AF in a single office ECG had significant prognostic implications with regard to mortality and CHF hospitalizations in patients with AF. These patients present a high-risk group and might benefit from intensified treatment.

Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline.

CLINICAL QUESTION: What are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice. CURRENT PRACTICE: Current guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing. RECOMMENDATION: The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old). HOW THIS GUIDELINE WAS CREATED: A guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. THE EVIDENCE: The systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years' follow-up. UNDERSTANDING THE RECOMMENDATION: The panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.

Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline

What are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice. Current guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing. The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying tobecome pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or youngadults (such as those ≤30 years old).

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).

Prediction of short-term prognosis in elderly patients with acute pulmonary embolism: validation of the RIETE score.

Essentials The RIETE score was derived to predict 10-day adverse outcomes in acute pulmonary embolism (PE). We externally validated the RIETE score in a prospective cohort of patients with PE. The RIETE score classified fewer patients as low-risk than currently recommended scores. The RIETE score was not superior to other scores in predicting 10-day adverse outcomes. SUMMARY: Introduction The Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) score was derived to identify patients with pulmonary embolism (PE) at low risk of overall complications. Objective To externally validate the RIETE score and compare its prognostic performance with the Pulmonary Embolism Severity Index (PESI), its simplified version (sPESI) and the Geneva Prognostic Score (GPS). Methods In a prospective multicenter cohort, we studied 687 elderly patients with acute PE. The primary outcome was 10-day overall complications (death, recurrent PE or major bleeding); the secondary outcome was 30-day overall mortality. We compared complications and mortality in low-risk vs. higher-risk patients and the area under the receiver operating characteristic (ROC) curve across scores. Results Overall, 27 patients (3.9%) had complications within 10 days and 22 (3.2%) died within 30 days. The RIETE score classified a smaller proportion of patients as low risk (31%) than the PESI (35%), sPESI (36%) and the GPS (90%). The proportion of low-risk patients based on the RIETE score, PESI, sPESI and GPS who had complications was 1.9%, 1.7%, 1.6% and 2.9%, respectively. The RIETE score had a lower area under the ROC curve (0.60) for predicting complications than the PESI (0.67), sPESI (0.65) and GPS (0.72). The area under the ROC curve for predicting mortality was similar (0.76-0.78) for all scores. Conclusion The RIETE score classified fewer patients as low risk than the other scores. It accurately identified patients at low risk of mortality but was not superior to other scores in predicting 10-day overall complications. TRIAL REGISTRATION: http://clinicaltrials.gov. Identifier: NCT00973596.

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

Frequency of use and acceptability of clinical prediction rules for pulmonary embolism among Swiss general internal medicine residents.

INTRODUCTION: Whether clinical prediction rules for pulmonary embolism are accepted and used among general internal medicine residents remains uncertain. We therefore evaluated the frequency of use and acceptability of the Revised Geneva Score (RGS) and the Pulmonary Embolism Severity Index (PESI), and explored which factors were associated with rule use. MATERIALS/METHODS: In an online survey among general internal medicine residents from 10 Swiss hospitals, we assessed rule acceptability using the Ottawa Acceptability of Decision Rules Instrument (OADRI) and explored the association between physician and training-related factors and rule use using mixed logistic regression models. RESULTS: The response rate was 50.4% (433/859). Overall, 61% and 36% of the residents reported that they always or regularly use the RGS and the PESI, respectively. The mean overall OADRI score was 4.3 (scale 0-6) for the RGS and 4.1 for the PESI, indicating a good acceptability. Rule acceptability (odds ratio [OR] 6.19 per point, 95% confidence interval [CI] 3.64-10.51), prior training in emergency medicine (OR 5.14, CI 2.20-12.01), and availability of internal guidelines recommending RGS use (OR 4.25, CI 2.15-8.43) were associated with RGS use. Rule acceptability (OR 6.43 per point, CI 4.17-9.92) and rule taught at medical school (OR 2.06, CI 1.24-3.43) were associated with PESI use. CONCLUSIONS: The RGS was more frequently used than the PESI. Both rules were considered acceptable. Rule acceptability, prior training in emergency medicine, availability of internal guidelines, and rule taught at medical school were associated with rule use and represent potential targets for quality improvement interventions.

Long-term outcomes of elderly patients with CYP2C9 and VKORC1 variants treated with vitamin K antagonists.

Essentials The long-term effects of VKORC1 and CYP2C9 variants on clinical outcomes remains unclear. We followed 774 patients ≥65 years with venous thromboembolism for a median duration of 30 months. Patients with CYP2C9 variants are at increased risk of death and non-major bleeding. Patients with genetic variants have a slightly lower anticoagulation quality only. SUMMARY: Background The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear. Objectives We examined the association between CYP2C9/VKORC1 variants and long-term clinical outcomes in a prospective cohort study of elderly patients treated with vitamin K antagonists for venous thromboembolism (VTE). Methods We followed 774 consecutive patients aged ≥ 65 years with acute VTE from nine Swiss hospitals for a median duration of 30 months. The median duration of initial anticoagulant treatment was 9.4 months. The primary outcome was the time to any clinical event (i.e. the composite endpoint of overall mortality, major and non-major bleeding, and recurrent VTE. Results Overall, 604 (78%) patients had a CYP2C9 or VKORC1 variant. Three hundred and thirty-four patients (43.2%) had any clinical event, 119 (15.4%) died, 100 (12.9%) had major and 167 (21.6%) non-major bleeding, and 100 had (12.9%) recurrent VTE. After adjustment, CYP2C9 (but not VKORC1) variants were associated with any clinical event (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.08-1.66), death (HR, 1.74; 95% CI, 1.19-2.52) and clinically relevant non-major bleeding (sub-hazard ratio [SHR], 1.39; 95% CI, 1.02-1.89), but not with major bleeding (SHR, 1.03; 95% CI, 0.69-1.55) or recurrent VTE (SHR, 0.95; 95% CI, 0.62-1.44). Patients with genetic variants had a slightly lower anticoagulation quality. Conclusions CYP2C9 was associated with long-term overall mortality and non-major bleeding. Although genetic variants were associated with a slightly lower anticoagulation quality, there was no relationship between genetic variants and major bleeding or VTE recurrence.

Omega-3 fatty acids predict recurrent venous thromboembolism or total mortality in elderly patients with acute venous thromboembolism.

Essentials The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) is unknown. Association of n-3 FAs with recurrent VTE or total mortality was investigated in 826 patients. Whole blood n-3 FAs were inversely correlated with recurrent VTE or total mortality. Major and non-major bleeding was not increased in patients with higher levels of n-3 FAs. SUMMARY: Background The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) remains unknown. Objectives To investigate the association of n-3 FAs with recurrent VTE or total mortality at 6 months and 3 years. Methods N-3 FAs were assessed in 826 patients aged ≥ 65 years, categorized into low, medium and high based on the 25th and 75th percentile. Mean follow-up was 29 months. Results At 6 months, subjects with medium (adjusted hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.62) and high n-3 FA levels (adjusted HR, 0.36; 95% CI, 0.20-0.67) were less likely to develop recurrent VTE or total mortality, compared with those with low n-3 FAs. At 3 years, medium levels (adjusted HR, 0.67; 95% CI, 0.47-0.96) were associated with lower risk of recurrent VTE or total mortality. As compared with low n-3 FAs, the adjusted sub-hazard ratio [SHR] of recurrent VTE was 0.39 (95% CI, 0.15-0.99) in patients with medium and 0.17 (95% CI, 0.03-0.82) in patients with high n-3 FAs. The cumulative incidence of recurrent VTE was lower in the medium and high n-3 FA groups as compared with the low n-3 FA groups, but seems to have worn off after 3 years. The incidence of major and non-major bleeding was not greater in the high n-3 FA group. Conclusion Higher levels of n-3 FAs were associated with a lower risk of recurrent VTE or total mortality in elderly patients with VTE, but not with greater bleeding risk.

Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study.

BACKGROUND: Venous thromboembolism (VTE) and subclinical thyroid dysfunction (SCTD) are both common in elderly patients. SCTD has been related to a hypercoagulable state and an increased thromboembolic risk. However, prospective data on the relationship between SCTD and VTE are lacking. OBJECTIVES: To investigate the relationship between SCTD and recurrent VTE (rVTE), all-cause mortality, and thrombophilic biomarkers. Patients Elderly patients with VTE were studied. METHODS: In a prospective multicenter cohort, thyroid hormones and thrombophilic biomarkers were measured 1 year after acute VTE, as both may be influenced by acute thrombosis. We defined subclinical hypothyroidism (SHypo) as elevated thyroid-stimulating hormone (TSH) levels (4.50-19.99 mIU L(-1) ), and subclinical hyperthyroidism (SHyper) as TSH levels of < 0.45 mIU L(-1) , both with normal free thyroxine levels. Outcomes were incidence of rVTE and overall mortality during follow-up starting after the 1-year blood sampling. RESULTS: Of 561 participants (58% with anticoagulation), 6% had SHypo and 5% had SHyper. After 20.8 months of mean follow-up, 9% developed rVTE and 10% died. The rVTE incidence rate was 7.2 (95% confidence interval [CI] 2.7-19.2) per 100 patient-years in SHypo participants, 0.0 (95% CI 0.0-7.6) in SHyper participants, and 5.9 (95% CI 4.4-7.8) in euthyroid participants. In multivariate analyses, the sub-hazard ratio for rVTE was 0.00 (95% CI 0.00-0.58) in SHyper participants and 1.50 (95% CI 0.52-4.34) in SHypo participants as compared with euthyroid participants, without increased levels of thrombophilic biomarkers. SHyper (hazard ratio [HR] 0.80, 95% CI 0.23-2.81) and SHypo (HR 0.99, 95% CI 0.30-3.29) were not associated with mortality. CONCLUSION: In elderly patients, SHyper may be associated with lower rVTE risks. SHypo showed a non-statistically significant pattern of an association with rVTE, without increased mortality or differences in thrombophilic biomarkers.

Physical activity and risk of bleeding in elderly patients taking anticoagulants.

BACKGROUND: Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. OBJECTIVES: To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. PATIENTS/METHODS: In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. CONCLUSIONS: A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

[Recommendations for management of dyslipidemia in 2014]. / Prise en charge des dyslipidémies en 2014.

Benefit of statin treatment is well established for secondary prevention. For primary prevention, good data exist to support use of statins in high-risk groups. Less data are available for intermediate risk group and very few patients at low risk have been included in clinical trials. In this context, an individual approach based on a risk stratification using PROCAM score adjusted for Switzerland is recommended. Lifestyle measures should be tried first. We also discuss the new American guidelines and their related controversies. Secondary causes and familiar forms of dyslipidemias, for which a risk assessment cannot be performed using risk scores (first cardiovascular event between age 20 and 60), should not be overlooked.

[How do Swiss family physicians treat subclinical hypothyroidism?]. / Comment tes médecins de famille prennent-ils en charge l'hypothyroïdie infraclinique?

Subclinical hypothyroidism is a common condition, and its prevalence increases with age. Currently, guidelines regarding the screening and treatment of subclinical hypothyroidism are controversial. An international survey of general practitioners (GPs), to which Swiss GPs also contributed, showed large inter-country variations in treatment strategies for subclinical hypothyroidism. These differences are mainly explained by the lack of strong evidence for the management of this condition. The European randomized-controlled clinical trial TRUST should help clarify recommendations for screening and thyroxin replacement for the elderly with subclinical hypothyroidism. Working in close collaboration with GPs in Switzerland for the recruitment of patients will ensure that the findings from this study will be applicable to primary care settings.