Bilateral axillary web syndrome in a patient with primary lymphoedema of upper limbs and non-Hodgkin lymphoma.

Primary lymphoedema, axillary web syndrome (AWS) and yellow nail syndrome may be related. Mr B is a 66-year-old gentleman with genital lymphoedema and lymphoedema of all four extremities. In 2023, he was diagnosed with non-Hodgkin lymphoma and also underwent cardiac surgery. In November 2023, he completed an inpatient rehabilitation at the Földi clinic in Germany, where he received intensive treatment for his lymphoedema and was also diagnosed with bilateral AWS. The presence of AWS in a patient with primary lymphoedema and no history of axillary surgery is unique. Although AWS typically presents after axillary surgery, this case highlights that it can also occur in patients without lymph node surgery. While the precise cause of this presentation of AWS is not known, it may be connected to yellow nail syndrome or potentially the recent chemotherapy treatment. This article will describe the clinical case, highlighting the need for further research on AWS present in primary lymphoedema.

Circulating Gal-3 and sST2 are associated with acute exercise-induced sustained endothelial activation: Possible relevance for fibrosis development?

Long-term, intense endurance exercise training can occasionally induce endothelial micro-damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well-trained male participants (10 runners and 10 cyclists) performed a strenuous high-intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal-3 and sST2 concentrations were investigated by enzyme-linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal-3 and sST2 concentrations and ECs were elevated after exercise (P < 0.001), without interaction between exercise modalities. Circulating Gal-3 and sST2 concentrations both showed a positive relationship with ECs (rrm  = 0.68, P = 0.001 and rrm  = 0.57, P = 0.010, respectively, both n = 18). The EC association with Gal-3 was significant only in cyclists, but equally strong for both modalities. Gal-3 was also related to exercise-induced CTi (rrm  = 0.57, P = 0.011, n = 18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise-released Gal-3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise-induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long-term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. NEW FINDINGS: What is the central question of this study? Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear. What is the main finding and its importance? We show that galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal-3 is an enhanced cardiac contractility. Acute exercise-released Gal-3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations.

Predictors for Unplanned Readmissions within 18 Days after Hospital Discharge: a Retrospective Cohort Study.

Since the introduction of the reimbursement system based on diagnosis-related groups (DRG) in Swiss hospitals in 2012, most readmissions occurring within 18 days and appertaining to the same major diagnostic category (MDC) are merged and thus often reimbursed to a lesser extent. While readmissions reflect increased distress for patients and their relatives, the causes are mainly patient-related and difficult to influence. However, it may be possible to identify cases at higher risk for readmission. Therefore, the aim of this study was to find predictors for early readmissions in the same MDC, to identify high-risk index hospitalizations and possibly prevent unnecessary readmissions. The data of all patients admitted to the Clinic of Internal Medicine at the University Hospital of Basel, Switzerland, hospitalized for longer than 24 hours during the pre-DRG period between October 2009 and September 2010 were retrospectively collected. Data were examined for predictors of unplanned readmission within 18 days under the same MDC ('relevant readmission') by means of logistic regression. 7479 patients (median age 67.8 years, 56% male) were admitted to the Clinic of Internal Medicine, with 232 patients (3.1%) being readmitted at least once. Logistic regression revealed male sex (p =0.035) and a high number of prescribed drugs at discharge (p <0.005) as patient-related predictors. The MDCs respiratory system, cardiovascular system, and gastrointestinal/hepatobiliary system were identified as high-risk categories (each p <0.005). Age and length of index hospital stay added no significant explanatory value to the regression model. Unplanned readmissions under the same MDC within 18 days were infrequent and not related to patients' age or length of hospital stay. Overall, multimorbid patients, and hospitalizations regarding the cardiovascular, respiratory, or gastrointestinal system appear to be most at risk and should therefore be specifically targeted in the prevention of early readmissions.

Prediction of Acute COPD Exacerbation in the Swiss Multicenter COPD Cohort Study (TOPDOCS) by Clinical Parameters, Medication Use, and Immunological Biomarkers.

BACKGROUND AND OBJECTIVE: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. METHOD: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. RESULTS: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. CONCLUSIONS: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD.

High-Intensity Interval Training for Heart Failure Patients With Preserved Ejection Fraction (HIT-HF)-Rational and Design of a Prospective, Randomized, Controlled Trial.

Background: The pathophysiology of HF with preserved ejection fraction (HFpEF) has not yet been fully understood and HFpEF is often misdiagnosed. Remodeling and fibrosis stimulated by inflammation appear to be main factors for the progression of HFpEF. In contrast to patients with HF with reduced ejection fraction, medical treatment in HFpEF is limited to relieving HF symptoms. Since mortality in HFpEF patients remains unacceptably high with a 5-year survival rate of only 30%, new treatment strategies are urgently needed. Exercise seems to be a valid option. However, the optimal training regime still has to be elucidated. Therefore, the aim of the study is to investigate the effects of a high-intensity interval (HIT) training vs. a moderate continuous training (MCT) on exercise capacity and disease-specific mechanisms in a cohort of patients with HFpEF. Methods: The proposed study will be a prospective, randomized controlled trial in a primary care setting including 86 patients with stable HFpEF. Patients will undergo measurements of exercise capacity, disease-specific blood biomarkers, cardiac and arterial vessel structure and function, total hemoglobin mass, metabolic requirements, habitual physical activity, and quality of life (QoL) at baseline and follow-up. After the baseline visit, patients will be randomized to the intervention or control group. The intervention group (n = 43) will attend a supervised 12-week HIT on a bicycle ergometer combined with strength training. The control group (n = 43) will receive an isocaloric supervised MCT combined with strength training. After 12 weeks, study measurements will be repeated in all patients to quantify the effects of the intervention. In addition, telephone interviews will be performed at 6 months, 1, 2, and 3 years after the last visit to assess clinical outcomes and QoL. Discussion: We anticipate clinically significant changes in exercise capacity, expressed as VO2peak, as well as in disease-specific mechanisms following HIT compared to MCT. Moreover, the study is expected to add important knowledge on the pathophysiology of HFpEF and the clinical benefits of a training intervention as a novel treatment strategy in HFpEF patients, which may help to improve both QoL and functional status in affected patients. Trial registration: ClinicalTrials.gov, identifier: NCT03184311, Registered 9 June 2017.

Point of care with serial NT-proBNP measurement in patients with acute decompensated heart failure as a therapy-monitoring during hospitalization (POC-HF): Study protocol of a prospective, unblinded, randomized, controlled pilot trial.

Despite important advances in diagnosis and medical therapy of heart failure (HF), disease monitoring and therapy guidance remains to be based on clinical signs and symptoms. NT-proBNP was repeatedly demonstrated to be a strong and independent predictor of morbidity and mortality in patients with HF. Only few - and conflicting - data are available on the efficacy of serial measurement of NT-proBNP as a tool for treatment monitoring in HF. These data are limited to the outpatient setting. Currently, no data are available on the effects of this approach in patients hospitalized for acute decompensated HF. The goal of this study is to explore whether the availability of serial NT-proBNP measurements may influence treatment decisions in patients with acute decompensated HF, and whether this leads to more rapid dose adjustments of prognostically beneficial medical therapies and earlier hospital discharge. In the intervention group, serial measurements of NT-proBNP every second business day are performed and made available to the treating physician, while no serial measurements are available in control group. HF therapy is left at the discretion of the treating physician. The primary endpoints are defined as the effects of monitoring NT-proBNP on medical HF therapy decisions, including type and dosing of medical therapies and the rapidity of adjustments, length of hospital stay, and evaluation of the changes in NT-proBNP values. Additional secondary endpoints include incidence of electrolyte imbalances and renal failure, changes in NYHA functional class, vital signs, body weight, quality of life, incidence of adverse events, transfer to Intensive Care Units, and mortality.

Adherence to GOLD Recommendations among Swiss Pulmonologists and General Practitioners.

Significant variability in adherence to COPD management recommendations has been reported. We aimed to evaluate real-life COPD pharmacotherapy prescribing patterns and adherence to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy in Switzerland. A questionnaire-based survey was conducted among Swiss general practitioners (GPs) and pulmonologists (PULs) from May 1 to November 30, 2017. Participants were invited to complete a questionnaire on their next 5-10 consecutive patients already receiving a pharmacological treatment for COPD. They were requested to assess dyspnea using the modified Medical Research Council (mMRC) dyspnea scale and to determine whether a treatment adjustment was indicated. Fifty-three PULs and 39 GPs completed questionnaires on 511 COPD patients. Dyspnea with mMRC grade ≥2 was reported in 62.5% of the patients, and 31.9% had had at least two exacerbations (or at least one with hospital admission) in the last 12 months. The vast majority (87.1%) of GOLD A patients were overtreated. In the GOLD B group, 52.2% of prescriptions were concordant with GOLD 2017 recommendations, but 37% of patients were overtreated. Among GOLD C patients, 49.2% received GOLD-adherent treatment and 47.5% were overtreated. In the GOLD D category, 78.8% of the patients received a treatment consistent with recommendations but 15.2% were undertreated. After reassessment of patient status, treatment was modified in 50.3% of the patients. This study confirms that discordance of real-world prescription patterns with international guidance is frequent. Further educational efforts are required to improve adherence to COPD management recommendations.

Effect of guideline revisions by the Swiss Society of Hypertension on blood pressure control in hypertensive patients from primary care.

  BACKGROUND: Recommendations for blood pressure goals have considerably changed across time, in particular for high-risk patients with diabetes mellitus and/or renal dysfunction. Before 2009, Swiss Society of Hypertension (SSH) guidelines recommended lowering blood pressure to <135/85 mm Hg and after 2009 to <130/80 mm Hg in high-risk patients. It remains unclear whether guideline changes for blood pressure targets are associated with reductions in blood pressure in hypertensive patients treated in primary care. The objective was to report the association between guideline change and blood pressure target achievement, as well as the prevalence of blood pressure target achievement according to guidelines and to identify factors associated with blood pressure target achievement in a Swiss primary care sample of treated hypertensive patients. METHODS: We used longitudinal data from the Swiss Hypertension Cohort Study, which was a prospective, observational study conducted by the Centre for Primary Health Care of the University of Basel from 2006 to 2013. General practitioners (GPs) enrolled 1003 patients attending their practice with a pre-existing diagnosis of arterial hypertension or office blood pressure measurement ≥140/90 mm Hg and assessed office blood pressure, cardiovascular risk factors, subclinical organ damage, diabetes mellitus, and established cardiovascular and renal disease. Mixed-effects regression models were used to estimate the associations of (1) the change in hypertension guidelines in 2009 with blood pressure and antihypertensive therapy in high-risk patients, and (2) cardiovascular risk factors with blood pressure target achievement in patients with complicated and uncomplicated hypertension. Models were adjusted for sociodemographic and health-related covariates. Missing data were imputed using a “multiple imputation by chained equation” approach. RESULTS: At baseline, hypertensive patients were on average 65.9 ± 12.5 years old and 55% were male. Blood pressure targets were achieved in 47% of patients with uncomplicated hypertension and in 13% of high-risk patients at baseline. In multivariable analyses adjusted for potential confounding factors, a visit by high-risk patients after 2009 was associated with decreased systolic office blood pressure (−5.40 mm Hg, 95% confidence interval [CI] −8.08 to 2.73) and a trend towards an increased use of pharmacological combination therapy (odds ratio [OR] 1.85, 95% CI 0.94 to 3.63; p = 0.073) compared with a visit before 2009. Neither a reduction of diastolic blood pressure nor an increase of blood pressure target achievement in high-risk patients was observed after 2009. High-risk patients were slightly more likely to achieve blood pressure targets at later follow-up visits than at baseline (OR 1.35, 95% CI 0.98 to 1.86; p = 0.068). In patients with uncomplicated hypertension, factors associated with the likelihood to achieve blood pressure goals were the increased use of pharmacological combination therapy (OR 1.19 per combination increase: e.g., dual therapy vs monotherapy, 95% CI 1.02 to 1.40), left ventricular hypertrophy (OR 0.58, 95% CI 0.36 to 0.93), older age (OR 1.19 per 10 years, 95% CI 1.02 to 1.40) and the number of follow-up examinations (OR 1.44 per follow-up visit, 95% CI 1.21 to 1.72). CONCLUSION: Overall, blood pressure goal attainment remains low for treated hypertensive patients followed up by primary care physicians in Switzerland. Independent of known confounding factors for blood pressure, the 2009 guideline change in high-risk patients was associated with a reduction in systolic office blood pressure together with an increase in pharmacological combination therapy. These results highlight primary care physicians’ efforts to implement blood pressure guidelines. Further, blood pressure goal attainment was more likely to be achieved in later follow-up visits, indicating that it takes time and regular follow-up visits with the GP to meet blood pressure goals.  .

Introduction of sacubitril/valsartan in primary care follow-up of heart failure: a prospective observational study (THESEUS).

AIMS: Switch from angiotensin converting enzyme inhibitor treatment to sacubitril/valsartan (sac/val) is associated with benefit in heart failure with reduced ejection fraction (HFrEF). Reports on management of this switch are largely based on randomized controlled trials, retrospective analyses, and hospital-based care, while patients with chronic heart failure (CHF) are frequently followed-up in primary care. The THESEUS study aimed to characterize the transition to sac/val and early maintenance period of HFrEF in primary care. METHOD AND RESULTS: THESEUS was a prospective, observational, non-interventional study, performed at primary care sites throughout Switzerland. Patient characteristics, sac/val transition, and maintenance were reported at study enrolment and approximately 3 and 6 months after sac/val initiation. The primary endpoint was achievement of 200 mg BID sac/val with maintenance for ≥12 weeks. Secondary outcomes included dosing regimens, healthcare utilization in the 6 months prior to sac/val initiation and during the study, patient well-being, safety, and tolerability. Fifty-eight patients with CHF were enrolled from 45 primary care centres. Six patients were excluded, and 19 achieved the primary endpoint (36.5%, Achievers). Non-Achievers underwent fewer titration steps than Achievers (1.9 ± 0.9 vs. 3.1 ± 1.4). In both groups, patient well-being improved and the percentage of New York Heart Association III patients decreased. Healthcare utilization decreased (19% vs. 30.8% in the 6 months pre-enrolment period). The most frequent reasons for target dose non-achievement were asymptomatic and symptomatic hypotension (15.3% and 12.1%, respectively). CONCLUSIONS: Results from THESEUS suggest that transition to sac/val is manageable in primary care, with a safety profile corresponding to reports from specialized heart failure care.

Does a tailored intervention to promote adherence in patients with chronic lung disease affect exacerbations? A randomized controlled trial.

BACKGROUND: Poor medication-adherence is common in chronic lung patients, resulting in reduced health-outcomes and increased healthcare-costs. This study aimed to investigate the impact of an acoustic reminder and support calls on adherence to inhaled therapy in asthma and COPD patients and to determine their effect on exacerbations. METHODS: This single-blinded randomized controlled trial investigated asthma and COPD patients during 6 months in an ambulatory setting. The intervention consisted of daily alarm clock and support phone calls, whenever use of rescue medication doubled or inhaled medication was not taken as prescribed. Primary outcome was time to next exacerbation. Frequency of exacerbations, adherence to inhaled medication and quality of life scores were secondary outcomes. Cox and Poisson regression were used to determine intervention effect on time to exacerbation and frequency of exacerbations, respectively. RESULTS: Seventy-five participants were assigned to the intervention group and 74 to usual follow-up care. During a median follow-up of 6.2 months, 22 and 28% in the intervention and control groups respectively, experienced at least one exacerbation. Intervention had no effect on time to first exacerbation (HR 0.65, 95% CI 0.21 to 2.07, P = .24), but showed a trend toward a 39% decreased frequency of exacerbations (RR = 0.61, 95% CI 0.35 to 1.03, P = .070) for the adjusted models, respectively. The intervention group had significantly more days with 80-100% taking adherence regarding puff inhalers (82 ± 14% vs. 60 ± 30%, P < .001) and dry powder capsules (90 ± .10% vs. 80 ± 21%, P = .01). Timing adherence in participants using puff inhalers was higher in the intervention group (69 ± 25% vs. 51 ± 33%, P < .001). No significant differences in QoL were found between the two groups. CONCLUSION: Participants assigned to the intervention group had significantly better taking and timing adherence of inhaled medication resulting in a trend towards a decreased frequency of exacerbations. However, no effect on time to next exacerbation was observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02386722, Registered 14 February 2014.

Reduction of corticosteroid use in outpatient treatment of exacerbated COPD - Study protocol for a randomized, double-blind, non-inferiority study, (The RECUT-trial).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately 4% to 7% of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are important in the treatment of acute COPD exacerbations and should be given for 5 to 7 days. Several studies suggest that corticosteroids accelerate the recovery of FEV1 (forced expiratory volume in 1 second), enhance oxygenation, decrease the duration of hospitalization, and improve clinical outcomes. However, the additional therapeutic benefit regarding FEV1 recovery appears to be most apparent in the first 3 to 5 days. No data are available on the optimum duration of corticosteroid treatment in primary-care patients with acute COPD exacerbations. Given that many COPD patients are treated as outpatients, there is an urgent need to improve the evidence base on COPD management in this setting. The aim of this study is to investigate whether a 3-day treatment with orally administered corticosteroids is non-inferior to a 5-day treatment in acute exacerbations of COPD in a primary-care setting. METHODS/DESIGN: This study is a prospective double-blind randomized controlled trial conducted in a primary-care setting. It is anticipated that 470 patients with acutely exacerbated COPD will be recruited. Participants are randomized to receive systemic corticosteroid treatment of 40 mg prednisone daily for 5 days (conventional arm, n = 235) or for 3 days followed by 2 days of placebo (experimental arm, n = 235). Antibiotic treatment for 7 days is given to all patients with CRP ≥ 50 mg/l, those with a known diagnosis of bronchiectasis, or those presenting with Anthonisen type I exacerbation. Additional treatment after inclusion is left at the discretion of the treating general practitioner. Follow-up visits are performed on days 3 and 7, followed by telephone interviews on days 30, 90, and 180 after inclusion in the study. The primary endpoint is the time to next exacerbation during the 6-month follow-up period. DISCUSSION: The study is designed to assess whether a 3-day course of corticosteroid treatment is not inferior to the conventional 5-day treatment course in outpatients with exacerbated COPD regarding time to next exacerbation. Depending on the results, this trial may lead to a reduction in the cumulative corticosteroid dose in COPD patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02386735. Registered on 12 March 2015.

Functional aging in health and heart failure: the COmPLETE Study.

BACKGROUND: Cardiovascular (CV) diseases including heart failure are the leading causes of morbidity, with age being the primary risk factor. The combination of age-related organic functional impairment and reduced physical fitness can drastically impact an individual's healthspan. One's lifespan can potentially be prolonged by the preservation or improvement of physical fitness. However, it remains unclear as to which biomarkers are most suitable for distinguishing between healthy aging and the impaired organ function associated with heart failure. Therefore, a comprehensive assessment of the components of physical fitness and CV function will be performed to identify the most important factors contributing to aging in relation to both health and disease. METHODS: This cross-sectional investigation will consist of two parts: COmPLETE-Health (C-Health) and COmPLETE-Heart (C-Heart). C-Health will examine the aging trajectories of physical fitness components and CV properties in a healthy population sample aged between 20 and 100 years (n = 490). Separately, C-Heart will assess the same markers in patients at different stages of chronic heart failure (n = 80). The primary outcome to determine the difference between C-Health and C-Heart will be cardiorespiratory fitness as measured by cardiopulmonary exercise testing on a bicycle ergometer. Secondary outcomes will include walking speed, balance, isometric strength, peak power, and handgrip strength. Physical activity as a behavioural component will be assessed objectively via accelerometry. Further, CV assessments will include pulse wave velocity; retinal, arterial, and venous diameters; brachial and retinal arterial endothelial function; carotid intima-media thickness; and systolic and diastolic function. The health distances for C-Health and C-Heart will be calculated using the methodology based on statistical (Mahalanobis) distance applied to measurements of quantitative biomarkers. DISCUSSION: This research seeks to identify physical fitness and CV biomarkers that best resemble underlying CV risk with age. Further, it will examine which physical fitness markers are impaired most in heart failure. The presented integrative approach could define new recommendations for diagnostic guidance in aging. Ultimately, this study is expected to offer a better understanding of which functional characteristics should be specifically targeted in primary and secondary prevention to achieve an optimal healthspan.

Factors Associated with Cardiorespiratory Fitness in a Swiss Working Population.

BACKGROUND: Good cardiorespiratory fitness (high VO2max) has beneficial effects on morbidity and mortality. Therefore, a tool to estimate VO2max in daily clinical practice is of great value for preventing chronic diseases in healthy adults. This study aimed at exploring the cardiometabolic profile in a representative Swiss working population. Based on these insights, a regression model was derived revealing factors associated with VO2max. METHODS: Cross-sectional data of 337 healthy and full-time employed adults recruited in the Basel region, Switzerland, were collected. Anthropometric measurements to compute body mass index (BMI) and waist circumference (WC) were performed. A 20-meter shuttle run test was conducted to determine individual VO2max. Heart rate (HR) was measured at rest, during maximal exertion, and two minutes after exercise. Systolic (SBP) and diastolic blood pressure (DBP) were assessed at rest and after exercise. A multiple linear regression model was built to identify a set of nonexercise predictor variables of VO2max. RESULTS: Complete data of 303 individuals (63% male) aged 18 to 61 years (mean 33 ± 12 years) were considered for analysis. The regression model (adjusted R2 = 0.647, SE = 5.3) identified sex (ß = -0.699, p < 0.001), WC (ß = -0.403, p < 0.001), difference of maximal to resting HR (ß = 0.234, p < 0.001), smoking (ß = -0.171, p < 0.001), and age (ß = -0.131, p < 0.01) as the most important factors associated with VO2max, while BMI, SBP, and DBP did not contribute to the regression model. CONCLUSIONS: This study introduced a simple model to evaluate VO2max based on nonexercise parameters as part of daily clinical routine without needing a time-consuming, cost-intense, and physically demanding direct assessment of VO2max. Knowledge about VO2max may help identifying individuals at increased cardiovascular risk and may provide the basis for health counselling and tailoring preventive measures.

Cardiovascular risk stratification in primary care patients with arterial hypertension: Results from the Swiss Hypertension Cohort Study (HccH).

AIMS: Few data are available on cardiovascular risk stratification in primary care patients treated for arterial hypertension. This study aimed at evaluating the cardiovascular risk profile of hypertensive patients included into the Swiss Hypertension Cohort Study according to the 2013 European Society of Hypertension/European Society of Cardiology Guidelines. METHODS: The Swiss Hypertension Cohort Study is a prospective, observational study conducted by the Centre for Primary Health Care of the University of Basel from 2006 to 2013. Patients with a diagnosis of arterial hypertension (office blood pressure measurement ≥140/90 mmHg) were enrolled. Office blood pressure measurement, cardiovascular risk factors, subclinical organ damage, diabetes mellitus, and established cardiovascular and renal disease were recorded at baseline and at an annual interval during routine consultations by general practitioners in Switzerland. RESULTS: In total, 1003 patients were eligible for analysis (55.6% male, mean age: 64.0 ± 13.2 years). At baseline, 78.5% of patients presented with either more than three additional cardiovascular risk factors, diabetes mellitus or subclinical organ damage, while 44.4% of patients had a high or very high overall cardiovascular risk. Cardiovascular risk factors and information about diabetes mellitus, established cardiovascular disease and renal disease were recorded mostly completely, whereas substantial gaps were revealed regarding the assessment of subclinical organ damage. CONCLUSION: The present findings demonstrate that the majority of primary care patients with arterial hypertension bear a substantial number of additional cardiovascular risk factors, subclinical and/or established organ damage. This emphasizes the need for continuous cardiovascular risk stratification and adequate treatment of arterial hypertension in Switzerland.

Predictive factors for exacerbation and re-exacerbation in chronic obstructive pulmonary disease: an extension of the Cox model to analyze data from the Swiss COPD cohort.

BACKGROUND: The Swiss COPD cohort was established in 2006 to collect data in a primary care setting. The objective of this study was to evaluate possible predictive factors for exacerbation and re-exacerbation. METHODS: In order to predict exacerbation until the next visit based on the knowledge of exacerbation since the last visit, a multistate model described by Therneau and Grambsch was performed. RESULTS: Data of 1,247 patients (60.4% males, 46.6% current smokers) were analyzed, 268 (21.5%) did not fulfill spirometric diagnostic criteria for COPD. Data of 748 patients (63% males, 44.1% current smokers) were available for model analysis. In order to predict exacerbation an extended Cox Model was performed. Mean FEV1/FVC-ratio was 53.1% (±11.5), with a majority of patients in COPD GOLD classes 2 or 3. Hospitalization for any reason (HR1.7; P = 0.04) and pronounced dyspnea (HR for mMRC grade four 3.0; P < 0.001) at most recent visit as well as prescription of short-acting bronchodilators (HR1.7; P < 0.001), inhaled (HR1.2; P = 0.005) or systemic corticosteroids (HR1.8; P = 0.015) were significantly associated with exacerbation when having had no exacerbation at most recent visit. Higher FEV1/FVC (HR0.9; P = 0.008) and higher FEV1 values (HR0.9; P = 0.001) were protective. When already having had an exacerbation at the most recent visit, pronounced dyspnea (HR for mMRC grade 4 1.9; P = 0.026) and cerebrovascular insult (HR2.1; P = 0.003) were significantly associated with re-exacerbation. Physical activity (HR0.6; P = 0.031) and treatment with long-acting anticholinergics (HR0.7; P = 0.044) seemed to play a significant protective role. In a best subset model for exacerbation, higher FEV1 significantly reduced and occurrence of sputum increased the probability of exacerbation. In the same model for re-exacerbation, coronary heart disease increased and hospitalization at most recent visit seemed to reduce the risk for re-exacerbation. CONCLUSION: Our data confirmed well-established risk factors for exacerbations whilst analyzing their predictive association with exacerbation and re-exacerbation. This study confirmed the importance of spirometry in primary care, not only for diagnosis but also as a risk evaluation for possible future exacerbations. TRIAL REGISTRATION: Our study got approval by local ethical committee in 2006 (EK Nr. 170/06) and was registered retrospectively on ClinicalTrials.gov (NCT02065921, 19th of February 2014).

Use and inhalation technique of inhaled medication in patients with asthma and COPD: data from a randomized controlled trial.

BACKGROUND: The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations. There are numerous reasons for the lack of disease control in asthma and COPD patients. It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient. This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence. METHODS: For this cross-sectional analysis, 165 asthma and COPD patients were analyzed. Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type. QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT). Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). RESULTS: Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (P = .02). Moreover, COPD patients with incorrect device application were more likely to suffer from cough (P = .03) and were more breathless while walking uphill or a flight of stairs (P = .02). While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (P = .04). CONCLUSIONS: Correct inhalation of prescribed medication is associated with improved health status and lung function. These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients' inhalation technique. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0238672 , Registered 14 February 2014.

Feasibility, acceptability and effectiveness of integrated care for COPD patients: a mixed methods evaluation of a pilot community-based programme.

QUESTION UNDER STUDY: The aim of this study was to assess the feasibility, acceptability and effectiveness of a pilot COPD integrated care programme implemented in Valais, Switzerland. METHODS: The programme was adapted from the self-management programme Living Well with COPD, and included the following elements: self-management patient-education group sessions, telephone and medical follow-ups, multidisciplinary teams, training of healthcare professionals, and evidence-based COPD care. A process and outcome evaluation of the pilot phase of the programme was conducted by means of qualitative and quantitative methods. Reach (coverage, participation rates), dosage (interventions carried out), fidelity (delivered as intended) and stakeholders' acceptance of the programme were evaluated through data monitoring and conduct of focus groups with patients and healthcare professionals. Effectiveness was assessed with pre-post analyses (before and after the intervention). The primary outcome measures were; (1) generic and disease-specific quality of life (36-Item Short Form Health Survey, Chronic Respiratory Questionnaire); and (2) hospitalisations (all-cause and for acute exacerbations) in the past 12 months. Secondary outcomes included self-efficacy, number of exacerbations and exercise capacity. Finally, controlled pre-post comparisons were also made with patients from the Swiss COPD Cohort for three common outcome measures (dyspnoea [mMRC score], number of exacerbations and smoking status). RESULTS: During the first 2 years of the programme, eight series of group-based education sessions were delivered to 57 patients with COPD in three different locations of the canton of Valais. Coverage objectives were achieved and attendance rate at the education sessions was high (83.6%). Patients' and healthcare professionals' reported a high degree of satisfaction, except for multidisciplinarity and transfer of information. Exploration of the effectiveness of this pilot programme suggested positive pre-post results at 12 months, with improvements in terms of health-related quality of life, self-efficacy, exercise capacity, immunisation coverage and Patient Assessment of Chronic Illness Care score. No other outcome, including the number of hospital admissions, differed significantly after 12 months. We observed no differences from the control group. CONCLUSIONS: The evaluation demonstrated the feasibility and acceptability of the programme and confirmed the relevance of mixed method process evaluation to adjust and improve programme implementation. The introduction of multidisciplinary teams in a context characterised by fragmentation of care was identified as the main challenge in the programme implementation and could not be achieved as expected. Despite this area for improvement, patients' feedback and early effectiveness results confirmed the benefits of COPD integrated care programmes emphasising self-management education.

Costs and benefits of diagnostic testing: four ways to improve patient care by purposive use of in vitro diagnostics.

Scientific advances and innovative targeted drugs, especially biologics, have revolutionised the treatment of many diseases. In oncology in particular, previously acute or lethal conditions have come to be considered chronic as new treatments have led to longer life expectancies and a lower rate of years lived with disability. These advances, however, come with rising costs in a resource-constrained environment. To achieve cost containment, reimbursement for in-vitro diagnostics (IVDs) is increasingly coming under pressure because they are perceived as a cost factor rather than as a tool to reduce expenditure in the long term. In this conceptual paper, we propose four possible interventions from an industry perspective that may contribute to increase effectiveness of IVD use to counteract increasing healthcare expenditures. These are: (1) fostering prevention, screening, early diagnosis and therapy; promoting (2) comprehensive and (3) stratified disease management; and (4) using targeted treatment alongside companion diagnostics. We conclude that the implementation of policies that promote a fee-for-outcome model rather than fee-for-service reimbursement can support sustainable healthcare.

Impact of an Electronic Monitoring Intervention to Improve Adherence to Inhaled Medication in Patients with Asthma and Chronic Obstructive Pulmonary Disease: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among patients with asthma and chronic obstructive pulmonary disease (COPD) is high and patients are frequently hospitalized due to exacerbations. Reasons for uncontrolled diseases are manifold, but are often associated with poor inhalation technique and non-adherence to the prescribed treatment plan. This causes substantial mortality, morbidity, and costs to the healthcare system. In this respect, the study of causes for non-adherence and the development of measures to increase and maintain treatment adherence in chronic diseases is of major clinical importance. OBJECTIVE: The primary objective of this study is to investigate the impact of using specific, validated electronic devices on adherence to inhaled medication in patients with chronic obstructive lung diseases such as asthma and COPD. Furthermore, it aims to assess the impact of a reminder and close supervision of the course of disease and quality of life. METHODS: In this ongoing prospective, single-blind, randomized controlled study, adherence to inhaled medication is analyzed over a 6-month period in at least 154 in- and outpatients with asthma or COPD who have experienced at least 1 exacerbation during the last year. Adherence is measured using electronic data capture devices, which save the date and time of each inhalative device actuation and transfer these data daily via a wireless connection to a Web-based database. Patients are randomly assigned to either the intervention or the control group. The clinical intervention consists of an automated and personal reminder. The intervention group receives an audio reminder and support calls in case medication has not been taken as prescribed or if rescue medication is used more frequently than pre-specified in the study protocol. During the study, participants are assessed every 2 months in the form of clinical visits. RESULTS: Recruitment started in January 2014. To date, a total of 169 patients have been recruited. Follow-up assessments are still ongoing. The study will be concluded in the first quarter of 2017. Data analysis will take place during 2017. CONCLUSIONS: Few studies have investigated medication adherence in patients with chronic obstructive lung diseases. With this prospective study design and the use of state-of-the-art devices for measuring adherence, we expect scientifically relevant and clinically meaningful results that will have a substantial and positive impact on the provision of healthcare in chronically ill patients suffering from asthma or COPD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02386722; https://clinicaltrials.gov/ct2/show/NCT02386722 (Archived by WebCite at http://www.webcitation.org/6oJq1fel0).

Association of Occupational and Leisure-Time Physical Activity with Aerobic Capacity in a Working Population.

INTRODUCTION: Objective data on the association of maximal aerobic capacity (VO2max) with work related physical activity are sparse. Thus, it is not clear whether occupational physical activity (OPA) contributes to an increase of VO2max. This study examined the association of VO2max with work and non-work related physical activity in a Swiss working population. METHODS: In this cross-sectional study, a total of 337 healthy and full-time employed adults were recruited. Demographic data, height, weight and BMI were recorded in all subjects. Participants were classified into nine occupational categories (ISCO-88) and merged into three groups with low, moderate, and high OPA. Physical activity was objectively measured by the SenseWear Mini Armband on seven consecutive days (23 hours per day). Participants were regarded as sufficiently active when accumulating ≥30 min of moderate-to-vigorous physical activity per day. VO2max was evaluated using the multistage 20-meter shuttle run test. RESULTS: Data of 303 participants were considered for analysis (63% male, age 33 yrs, SD 12). Multiple linear regression analysis (adjusted R2 = 0.69) revealed significant positive associations of VO2max with leisure-time physical activity (LTPA) at vigorous intensity (ß = 0.212) and sufficient moderate-to-vigorous physical activity (ß = 0.100) on workdays. Female gender (ß = -0.622), age (ß = -0.264), BMI (ß = -0.220), the ratio of maximum to resting heart rate (ß = 0.192), occupational group (low vs. high OPA, ß = -0.141), and smoking (ß = -0.133) were also identified as independent predictors of VO2max. CONCLUSIONS: The present results suggest that VO2max is positively associated with LTPA, but not with OPA on workdays. This finding emphasizes the need for employees to engage in sufficient high-intensity physical activity in recreation for maintaining or improving VO2max with regard to health benefits.