[Cascade genetic testing of familial hypercholesterolemia A new opportunity for prevention]. / Dépistage génétique en cascade de l'hypercholestérolémie familiale - Une nouvelle opportunité pour la prévention cardiovasculaire.

Familial hypercholesterolemia (FH) is a genetic disorder associated with an increased risk of early-onset cardiovascular events. Because lifestyle interventions and lipid-lowering drugs can strongly reduce cardiovascular risk, the early diagnosis of FH is important. Indeed, given the autosomal dominant transmission of the pathogenic variant, a genetic cascade screening program of first-degree relatives from an index case could identify patients at high cardiovascular risk. In Switzerland, genetic testing for FH is rarely used, because it is not reimbursed by health insurance companies. To test the usefulness of cascade genetic testing for FH, the CATCH study is currently ongoing in all linguistic part of Switzerland.

L'hypercholestérolémie familiale (HF) est une maladie génétique associée à un risque augmenté d'événements cardiovasculaires précoces. Étant donné que les adaptations du style de vie et les traitements hypolipémiants peuvent réduire fortement le risque cardiovasculaire, le diagnostic précoce de l'HF est important. À cette fin, en raison de la transmission autosomique dominante du variant pathogène, un dépistage génétique en cascade des apparentés du premier degré organisé autour du cas index permettrait d'identifier précocement les patients à risque cardiovasculaire élevé. Cependant, le test génétique est très peu utilisé en Suisse, car il n'est pas remboursé par les caisses-maladie. Afin de tester l'utilité du dépistage génétique en cascade de l'HF, l'étude CATCH est en cours actuellement dans les trois régions linguistiques de Suisse.

NOACs in Anesthesiology.

BACKGROUND: Due to increasing use of new oral anticoagulants (NOACs), clinicians are faced more and more frequently with clinical issues related to these drugs. OBJECTIVE: The objective of this publication is to make practical suggestions for the perioperative management of NOACs as well as for their handling in overdoses and bleedings. RECOMMENDATIONS: In elective surgery and creatinine clearance ≥ 50 ml/min, a NOAC should be discontinued 24-36 h before the intervention, and even earlier in case of reduced kidney function. In emergency interventions that cannot be delayed, the management is dependent on the NOAC plasma levels. With levels ≤ 30 ng/ml, surgery can be performed. With levels >30 ng/ml, reversal agents should be considered. In low bleeding risk surgery, NOACs can be re-started 24 h after the intervention, which is prolonged to 48-72 h after surgery with high bleeding risk. In case of NOAC overdose and minor bleedings, temporary discontinuation and supportive care are usually sufficient to control the situation. In severe or life-threatening bleedings, nonspecific and specific reversal agents should be considered.

Influence of obesity on the outcome of non-surgical periodontal therapy - a systematic review.

BACKGROUND: Obesity and periodontitis are important chronic health problems. Obesity is associated with an increased prevalence of periodontitis. Whether obesity also affects the outcome of non-surgical periodontal therapy is to date still unclear. METHODS: A systematic review of studies referenced in SCOPUS, MEDLINE, PubMed, Cochrane, CINAHL, Biosis and Web of Science was performed. Titles, abstracts and finally full texts were scrutinized for possible inclusion by two independent investigators. Quality and heterogeneity of the studies were assessed and the study designs were examined. Probing pocket depth reduction was analyzed as primary surrogate parameter for therapeutic success after non-surgical periodontal therapy. RESULTS: One-hundred-and-fifty-nine potentially qualifying studies were screened. Eight studies fulfilled the inclusion criteria and were analyzed. Three of eight studies failed to show an influence of obesity on pocket depth reduction after non-surgical therapy. The remaining five studies documented a clear negative effect on the outcome of non-surgical periodontal therapy. The finally included studies did not correspond to the highest level of quality (RCTs). Due to the heterogeneity of the data a meta-analysis was not possible. CONCLUSION: The literature on the effect of obesity on the treatment outcome of non-surgical periodontal therapy remains controversial. The data, however, support that obesity is not only a factor associated with poorer periodontal health but might also result in inferior response to non-surgical treatment of periodontitis.

Effect of dairy consumption on cognition in older adults: A population-based cohort study.

OBJECTIVE: We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy. DESIGN: Secondary analysis of a prospective population-based cohort study. PARTICIPANTS: We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland. MEASUREMENTS: The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes. METHODS: Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up. RESULTS: Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (-3% to 26.5%)] and eggs [18% (2.3%-33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes. CONCLUSION: We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results.

Is electrical cardioversion independently associated with infarcts on brain magnetic resonance imaging or clinical outcomes in patients with atrial fibrillation?

BACKGROUND: Electrical cardioversion (ECV) is frequently performed in symptomatic atrial fibrillation. OBJECTIVE: This study aimed to assess the association of ECV with infarcts on brain magnetic resonance imaging (bMRI) and clinical outcomes. METHODS: The Swiss Atrial Fibrillation Cohort Study included 2386 patients; 1731 patients were evaluated by bMRI. ECVs were recorded by questionnaire. Patients were assigned to categories by number of ECVs performed before enrollment (0, 1, ≥2). A bMRI study was conducted at baseline and after 2 years (n = 1227) and analyzed for large noncortical or cortical infarcts and small noncortical infarcts. Clinical outcomes were recorded during follow-up. Associations of ECV and outcome measures were assessed by multivariate analyses. RESULTS: There was no independent association between the number of ECVs and infarct prevalence (large noncortical or cortical infarcts and small noncortical infarcts) on baseline bMRI (ECV 1 vs 0: odds ratio [OR], 0.95 [95% CI, 0.68-1.24]; ECV ≥2 vs 0: OR, 1.04 [0.72-1.44]) or between ECVs performed during follow-up and new infarcts on bMRI at 2 years (OR, 1.46 [0.54-3.31]). ECVs were not associated with overt stroke or transient ischemic attack (ECV 1 vs 0: hazard ratio [HR], 1.36 [0.88-2.10]; ECV ≥2 vs 0: HR, 1.53 [0.94-2.48]), hospitalization for heart failure (ECV 1 vs 0: HR, 1.06 [0.82-1.37]; ECV ≥2 vs 0: HR, 1.03 [0.77-1.38]), or death (ECV 1 vs 0: HR, 0.90 [0.70-1.15]; ECV ≥2 vs 0: HR, 0.91 [0.69-1.20]). CONCLUSION: There was no association between ECV performed before enrollment and cerebral infarcts on baseline bMRI or between ECV performed during follow-up and new infarcts at 2 years. Moreover, ECV was not associated with clinical events.

Long-Term Mortality after New-Onset Atrial Fibrillation in COVID-19.

Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and has been suggested to be a potential risk factor for a poor clinical outcome. Methods: In this observational study, all patients hospitalized due to COVID-19 in 2020 in the Cantonal Hospital of Baden were included. We assessed clinical characteristics, in-hospital outcomes as well as long-term outcomes with a mean follow-up time of 278 (±90) days. Results: Amongst 646 patients diagnosed with COVID-19 (59% male, median age: 70 (IQR: 59-80)) in 2020, a total of 177 (27.4%) patients were transferred to the intermediate/intensive care unit (IMC/ICU), and 76 (11.8%) were invasively ventilated during their hospitalization. Ninety patients (13.9%) died. A total of 116 patients (18%) showed AF on admission of which 34 (29%) had new-onset AF. Patients with COVID-19 and newly diagnosed AF were more likely to require invasive ventilation (OR: 3.5; p = 0.01) but did not encounter an increased in-hospital mortality. Moreover, AF neither increased long-term mortality nor the number of rehospitalizations during follow-up after adjusting for confounders. Conclusions: In patients suffering from COVID-19, the new-onset of AF on admission was associated with an increased risk of invasive ventilation and transfer to the IMC/ICU but did not affect in-hospital or long-term mortality.

Trimethylamine-N-oxide is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation.

OBJECTIVE: Trimethylamine-N-oxide (TMAO) is a metabolite derived from the microbial processing of dietary phosphatidylcholine and carnitine and the subsequent hepatic oxidation. Due to its prothrombotic and inflammatory mechanisms, we aimed to assess its role in the prediction of adverse events in a susceptible population, namely patients with atrial fibrillation. METHODS: Baseline TMAO plasma levels were measured by liquid chromatography-tandem mass spectrometry in 2379 subjects from the ongoing Swiss Atrial Fibrillation cohort. 1722 underwent brain MRI at baseline. Participants were prospectively followed for 4 years (Q1-Q3: 3.0-5.0) and stratified into baseline TMAO tertiles. Cox proportional hazards and linear and logistic mixed effect models were employed adjusting for risk factors. RESULTS: Subjects in the highest TMAO tertile were older (75.4±8.1 vs 70.6±8.5 years, p<0.01), had poorer renal function (median glomerular filtration rate: 49.0 mL/min/1.73 m2 (35.6-62.5) vs 67.3 mL/min/1.73 m2 (57.8-78.9), p<0.01), were more likely to have diabetes (26.9% vs 9.1%, p<0.01) and had a higher prevalence of heart failure (37.9% vs 15.8%, p<0.01) compared with patients in the lowest tertile. Oral anticoagulants were taken by 89.1%, 94.0% and 88.2% of participants, respectively (from high to low tertiles). Cox models, adjusting for baseline covariates, showed increased total mortality (HR 1.65, 95% CI 1.17 to 2.32, p<0.01) as well as cardiovascular mortality (HR 1.86, 95% CI 1.21 to 2.88, p<0.01) in the highest compared with the lowest tertile. When present, subjects in the highest tertile had more voluminous, large, non-cortical and cortical infarcts on MRI (log-transformed volumes; exponentiated estimate 1.89, 95% CI 1.11 to 3.21, p=0.02) and a higher chance of small non-cortical infarcts (OR 1.61, 95% CI 1.16 to 2.22, p<0.01). CONCLUSIONS: High levels of TMAO are associated with increased risk of cardiovascular mortality and cerebral infarction in patients with atrial fibrillation. TRIAL REGISTRATION NUMBER: NCT02105844.

Estimating the cost impact of atrial fibrillation using a prospective cohort study and population-based controls.

AIMS: Atrial fibrillation (AF) costs are expected to be substantial, but cost comparisons with the general population are scarce. Using data from the prospective Swiss-AF cohort study and population-based controls, we estimated the impact of AF on direct healthcare costs from the Swiss statutory health insurance perspective. METHODS: Swiss-AF patients, enrolled from 2014 to 2017, had documented, prevalent AF. We analysed 5 years of follow-up, where clinical data, and health insurance claims in 42% of the patients were collected on a yearly basis. Controls from a health insurance claims database were matched for demographics and region. The cost impact of AF was estimated using five different methods: (1) ordinary least square regression (OLS), (2) OLS-based two-part modelling, (3) generalised linear model-based two-part modelling, (4) 1:1 nearest neighbour propensity score matching and (5) a cost adjudication algorithm using Swiss-AF data non-comparatively and considering clinical data. Cost of illness at the Swiss national level was modelled using obtained cost estimates, prevalence from the Global Burden of Disease Project, and Swiss population data. RESULTS: The 1024 Swiss-AF patients with available claims data were compared with 16 556 controls without known AF. AF patients accrued CHF5600 (EUR5091) of AF-related direct healthcare costs per year, in addition to non-AF-related healthcare costs of CHF11100 (EUR10 091) per year accrued by AF patients and controls. All five methods yielded comparable results. AF-related costs at the national level were estimated to amount to 1% of Swiss healthcare expenditure. CONCLUSIONS: We robustly found direct medical costs of AF patients were 50% higher than those of population-based controls. Such information on the incremental cost burden of AF may support healthcare capacity planning.

Patient clusters and cost trajectories in the Swiss Atrial Fibrillation cohort.

OBJECTIVE: Evidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories. METHODS: Swiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017. Patient clusters were identified using hierarchical cluster analysis of baseline characteristics. Ongoing yearly follow-ups include health insurance clinical and claims data. An algorithm was developed to adjudicate costs to AF and related complications. RESULTS: A subpopulation of 1024 Swiss-AF patients with available claims data was followed up for a median (IQR) of 3.24 (1.09) years. Average yearly AF-adjudicated costs amounted to SFr5679 (€5163), remaining stable across the observation period. AF-adjudicated costs consisted mainly of inpatient and outpatient AF treatment costs (SFr4078; €3707), followed by costs of bleeding (SFr696; €633) and heart failure (SFr494; €449). Hierarchical analysis identified three patient clusters: cardiovascular (CV; N=253 with claims), isolated-symptomatic (IS; N=586) and severely morbid without cardiovascular disease (SM; N=185). The CV cluster and SM cluster depicted similarly high costs across all cost outcomes; IS patients accrued the lowest costs. CONCLUSION: Our results highlight three well-defined patient clusters with specific costs that could be used for stratification in both clinical and economic studies. Patient characteristics associated with adjudicated costs as well as cost trajectories may enable an early understanding of the magnitude of upcoming AF-related healthcare costs.

Role of age, sex, and specific provoking factors on the distal versus proximal presentation of first symptomatic deep vein thrombosis: analysis of the SWIss Venous ThromboEmbolism Registry (SWIVTER).

We aimed to evaluate the impact of age, sex, and their interactions with provoking risk factors for deep vein thrombosis (DVT). In addition, we intended to provide additional insights on risk factors associated with the isolated distal versus proximal presentation of first symptomatic acute DVT, both being characterized by different prognosis. In the present analysis from the SWIss Venous ThromboEmbolism Registry (SWIVTER), we compared demographic and baseline characteristics in patients with isolated distal (n = 184; 35%) versus proximal (n = 346) DVT of the lower limbs without symptomatic pulmonary embolism, and identified factors related with the presenting thrombosis location. In the overall population, mean age was 59 ± 19 years, 266 (50%) were women, 106 (20%) patients had cancer, 86 (16%) recent surgery, and 52 (10%) acute infection/sepsis. In a multivariable analysis, recent surgery [odds ratio (OR) 2.92, 95% confidence interval (CI) 1.80-4.73] was independently associated with a diagnosis of isolated distal DVT, whereas cancer (OR 2.01, 95% CI 1.20-3.35), male sex aged 41 to 75 years (OR 2.21, 95% CI 1.33-3.67), and acute infection/sepsis (OR 2.71, 95% CI 1.29-5.66) with a diagnosis of proximal DVT. In SWIVTER, age, sex, and several provoking risk factors for VTE appeared to be related with the presenting location of first symptomatic DVT. Cancer, male sex, and acute infection/sepsis were associated with a proximal location of DVT, whereas recent surgery was associated with a distal presentation, likely acting as confounders for the association between thrombosis location and prognosis.

Swiss general internal medicine board examination: quantitative effects of publicly available and unavailable questions on question difficulty and test performance.

BACKGROUND: Formerly, a substantial number of the 120 multiple-choice questions of the Swiss Society of General Internal Medicine (SSGIM) board examination were derived from publicly available MKSAP questions (Medical Knowledge Self-Assessment Program®). The possibility to memorise publicly available questions may unduly influence the candidates' examination performance. Therefore, the examination board raised concerns that the examination did not meet the objective of evaluating the application of knowledge. The society decided to develop new, "Helvetic" questions to improve the examination. The aim of the present study was to quantitatively assess the degree of difficulty of the Helvetic questions (HQ) compared with publicly available and unavailable MKSAP questions and to investigate whether the degree of difficulty of MKSAP questions changed over time as their status changed from publicly available to unavailable. METHODS: The November 2019 examination consisted of 40 Helvetic questions, 40 publicly available questions from MKSAP edition 17 (MKSAP-17) and 40 questions from MKSAP-15/16, which were no longer publicly available at the time of the examination. An one factorial univariate analysis of variance (ANOVA) examined question difficulty (lower values mean higher difficulty) between these three question sets. A repeated ANOVA compared the difficulty of MKSAP-15/16 questions in the November 2019 examination with the difficulty of the exact same questions from former examinations, when these questions belonged to the publicly available MKSAP edition. The publicly available MKSAP-17 and the publicly unavailable Helvetic questions served as control. RESULTS: The analysis of the November 2019 exam showed a significant difference in average item difficulty between Helvetic and MKSAP-17 questions (71% vs 86%, p <0.001) and between MKSAP-15/16 and MKSAP-17 questions (70% vs 86%, p <0.001). There was no significant difference in item difficulty between Helvetic and MKSAP-15/16 questions (71% vs 70%, p = 0.993). The repeated measures ANOVA on question use and the three question categories showed a significant interaction (p <0.001, partial eta-squared = 0.422). The change in the availability of MKSAP-15/16 questions had a strong effect on difficulty. Questions became on average 21.9% more difficult when they were no longer publicly available. In contrast, the difficulty of the MKSAP-17 and Helvetic questions did not change significantly across administrations. DISCUSSION: This study provides the quantitative evidence that the public availability of questions has a decisive influence on question difficulty and thus on SSGIM board examination performance. Reducing the number of publicly available questions in the examination by introducing confidential, high-quality Helvetic questions contributes to the validity of the board examination by addressing higher order cognitive skills and making rote-learning strategies less effective.

Negative myoclonus as the leading symptom in acute cefepime neurotoxicity.

An 86-year-old woman was diagnosed with hospital-acquired pneumonia with Pseudomonas aeruginosa and treated with cefepime adjusted to her renal clearance. After 4 days, she developed acute-onset negative myoclonus without signs of altered mental status. After ruling out an acute intracranial haemorrhagic or ischaemic stroke as well as other metabolic and endocrine causes of negative myoclonus, the antibiotic was switched to piperacillin/tazobactam due to a suspicion of cefepime neurotoxicity. The patient improved within 24 hours and her symptoms fully resolved within 4 days. These observations suggest a link of the negative myoclonus to acute cefepime neurotoxicity, which may occur without or with minimal alteration of mental status, thus extending its spectrum of clinical presentation.

Right ventricular thrombus, a challenge in imaging diagnostics: a case series.

BACKGROUND: Presence of right ventricular thrombus (RVT) is a rare but life-threatening condition, thus immediate diagnosis and therapy are mandatory. Unfortunately, detection and distinction from intraventricular tumour masses or vegetations represent a complex task. Furthermore, consecutive therapy is principally led by clinical presentation without considering morphological features of the thrombus. Current literature suggests a multimodal non-invasive imaging approach. In this article, we discuss the role of cardiac magnetic resonance imaging (CMR) for the detection of RVT in patients with pulmonary embolism (PE). We consider the relatively expensive and not broadly available imaging procedure and weigh it up to its assumed high sensitivity, specificity, and importance for differential diagnosis and therapeutic decision-making. CASE SUMMARY: In this case series, we report three cases of RVT with concomitant PE, whereof two were missed during routine cardiac workup by transthoracic echocardiography and computer tomography. Cardiac magnetic resonance imaging led to detection and further characterization of the thrombi in both cases. CONCLUSIONS: Cardiac magnetic resonance imaging reliably detects and characterizes RVT, even under unfavourable conditions for echocardiography such as arrhythmia, adiposity, or in posterior position of RVT. Obtained information could facilitate the choice of therapeutic approach (anticoagulation vs. systemic lysis vs. surgical thrombectomy). Future risk stratification scores will promote cost-effective use of CMR.

Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE).

INTRODUCTION: The clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this condition receive anticoagulant treatment, which is associated with a 90-day risk of recurrent venous thromboembolism (VTE) of 0.8% and major bleeding of up to 5%. Given the ongoing controversy concerning the risk-benefit ratio of anticoagulation for isolated SSPE and the lack of evidence from randomised-controlled studies, the aim of this clinical trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE. METHODS AND ANALYSIS: SAFE-SSPE (Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism, a multicentre randomised placebo-controlled non-inferiority trial) is an international, multicentre, placebo-controlled, double-blind, parallel-group non-inferiority trial conducted in Switzerland, the Netherlands and Canada. Low-risk patients with isolated SSPE are randomised to receive clinical surveillance with either placebo (no anticoagulation) or anticoagulant treatment with rivaroxaban. All patients undergo bilateral whole-leg compression ultrasonography to exclude concomitant deep vein thrombosis before enrolment. Patients are followed for 90 days. The primary outcome is symptomatic recurrent VTE (efficacy). The secondary outcomes include clinically significant bleeding and all-cause mortality (safety). The ancillary outcomes are health-related quality of life, functional status and medical resource utilisation. ETHICS AND DISSEMINATION: The local ethics committees in Switzerland have approved this protocol. Submission to the Ethical Committees in the Netherlands and Canada is underway. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04263038.

The well-being of Swiss general internal medicine residents.

BACKGROUND: Physician well-being has an impact on productivity and quality of care. Residency training is a particularly stressful period. OBJECTIVE: To assess the well-being of general internal medicine (GIM) residents and its association with personal and work-related factors. METHODS: We conducted an anonymous electronic survey among GIM residents from 13 Swiss teaching hospitals. We explored the association between a reduced well-being (≥5 points based on the Physician Well-Being Index [PWBI]) and personal and work-related factors using multivariable mixed-effects logistic regression. RESULTS: The response rate was 54% (472/880). Overall, 19% of residents had a reduced well-being, 60% felt burned out (emotional exhaustion), 47% were worried that their work was hardening them emotionally (depersonalisation), and 21% had career choice regret. Age (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05–1.34), working hours per week (OR 1.04 per hour, 95% CI 1.01–1.07) and <2.5 rewarding work hours per day (OR 3.73, 95% CI 2.01–6.92) were associated with reduced well-being. Administrative workload and satisfaction with the electronic medical record were not. We found significant correlations between PWBI score and job satisfaction (rs = -0.54, p<0.001), medical errors (rs = 0.18, p<0.001), suicidal ideation (rs = 0.12, p = 0.009) and the intention to leave clinical practice (rs = 0.38, p <0.001) CONCLUSIONS: Approximately 20% of Swiss GIM residents appear to have a reduced well-being and many show signs of distress or have career choice regret. Having few hours of rewarding work and a high number of working hours were the most important modifiable predictors of reduced well-being. Healthcare organisations have an ethical responsibility to implement interventions to improve physician well-being.

Clinical presentation and outcomes in elderly patients with symptomatic isolated subsegmental pulmonary embolism.

OBJECTIVES: Data are limited on clinical presentation and outcomes in elderly patients with acute symptomatic isolated subsegmental pulmonary embolism (SSPE). We compared clinical presentation, risk factors, processes of care, and outcomes between elderly patients with SSPE and patients with more proximal pulmonary embolism (PE). METHODS: We prospectively followed 578 patients aged ≥65 years with acute symptomatic isolated SSPE or proximal PE in a multicentre Swiss cohort study. We compared quality of life at three months using the PEmb-QoL, and examined the independent association between localization of PE and clinical outcomes (recurrent venous thromboembolism [VTE], overall mortality) using regression models with adjustment for potential confounders. RESULTS: Overall, 11% of patients had isolated SSPE. Patients with SSPE were less likely to have a pulse ≥110/min (3% vs. 13%), but more likely to have active cancer (28% vs. 15%) and to receive outpatient care (11% vs. 4%) than patients with proximal PE. Virtually all patients (98%) with SSPE received anticoagulants. Quality of life did not differ between the groups at 3 months. No patient with SSPE vs. seven patients with proximal PE died from the index PE event. No significant difference was observed for the 3-year cumulative incidence of recurrent VTE (7% vs. 12%) and death (29% vs. 20%). After adjustment, SSPE was not associated with a lower risk of clinical outcomes than proximal PE. CONCLUSIONS: Clinical presentation and incidences of adverse outcomes did not differ significantly between elderly patients with SSPE or proximal PE, although the power to detect differences might have been limited given the small number of events. Thus, our study does not provide evidence that unselected, elderly patients with SSPE have a more benign clinical course.

Statin therapy and recurrent venous thromboembolism in the elderly: a prospective cohort study.

Previous studies reported lower rates of recurrent venous thromboembolism (rVTE) among statin users, but this association could be influenced by concurrent anticoagulation and confounding by statin indication. This study aimed to confirm the beneficial association between statins and rVTE, stratified according to periods with and without anticoagulation, and additionally employ propensity score weighted approach to reduce risk of confounding by indication. The setting was a prospective multicentre cohort study and the outcome was time to first rVTE in statin vs. non-statin users. 980 participants with acute VTE were enrolled (mean age 75.0 years, 47% women), with median follow-up of 2.5 years. Of 241 (24.3%) statin users, 21 (8.7%) suffered rVTE vs. 99 (13.4%) among 739 non-users. The overall adjusted sub-hazard ratio (aSHR) for rVTE comparing statin users to non-users was 0.72 (95%CI 0.44 to 1.19, p = 0.20). This association was only apparent during periods without anticoagulation (aSHR 0.50, 95%CI 0.27 to 0.92, p = 0.03; vs. with anticoagulation: aSHR 1.34, 95%CI 0.54 to 3.35, p = 0.53). Using propensity scores, the rVTE risk during periods without anticoagulation fell further (aSHR 0.20, 95%CI 0.08 to 0.49, p < 0.001). In conclusion, statin use is associated with a more pronounced risk reduction for rVTE than previously estimated, but only during periods without anticoagulation.

Predictors and Outcomes of Recurrent Venous Thromboembolism in Elderly Patients.

BACKGROUND: Little is known about predictors and outcomes of recurrent venous thromboembolism in elderly patients. METHODS: We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was symptomatic recurrent venous thromboembolism. We explored the association between baseline characteristics and treatments and recurrent venous thromboembolism using competing risk regression, adjusting for periods of anticoagulation as a time-varying covariate. We also assessed the clinical consequences (case-fatality, localization) of recurrent venous thromboembolism. RESULTS: During a median follow-up period of 30 months, 122 patients developed recurrent venous thromboembolism, corresponding to a 3-year cumulative incidence of 14.8%. The case-fatality of recurrence was high (20.5%), particularly in patients with unprovoked (23%) and cancer-related venous thromboembolism (29%). After adjustment, only unprovoked venous thromboembolism (sub-hazard ratio, 1.67 compared with provoked venous thromboembolism; 95% confidence interval, 1.00-2.77) and proximal deep vein thrombosis (sub-hazard ratio, 2.41 compared with isolated distal deep vein thrombosis; 95% confidence interval, 1.07-5.38) were significantly associated with recurrence. Patients with initial pulmonary embolism were more likely to have another pulmonary embolism as a recurrent event than patients with deep vein thrombosis. CONCLUSIONS: Elderly patients with acute venous thromboembolism have a substantial long-term risk of recurrent venous thromboembolism, and recurrence carries a high case-fatality rate. Only 2 factors, unprovoked venous thromboembolism and proximal deep vein thrombosis, were independently associated with recurrent venous thromboembolism, indicating that traditional risk factors for venous thromboembolism recurrence (eg, cancer) may be less relevant in the elderly.