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AIMS: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass. METHODS: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering. RESULTS: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9–36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (

Abstract Background Lower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED). Methods The PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning. Discussion The PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful. The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance. Trial registration This study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406. Trial status Recruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023.

BackgroundPatient adherence to medications can be assessed using interactive digital health technologies such as electronic monitors (EMs). Changes in treatment regimens and deviations from EM use over time must be characterized to establish the actual level of medication adherence. ObjectiveWe developed the computer script CleanADHdata.R to clean raw EM adherence data, and this tutorial is a guide for users. MethodsIn addition to raw EM data, we collected adherence start and stop monitoring dates and identified the prescribed regimens, the expected number of EM openings per day based on the prescribed regimen, EM use deviations, and patients’ demographic data. The script formats the data longitudinally and calculates each day’s medication implementation. ResultsWe provided a simulated data set for 10 patients, for which 15 EMs were used over a median period of 187 (IQR 135-342) days. The median patient implementation before and after EM raw data cleaning was 83.3% (IQR 71.5%-93.9%) and 97.3% (IQR 95.8%-97.6%), respectively (Δ+14%). This difference is substantial enough to consider EM data cleaning to be capable of avoiding data misinterpretation and providing a cleaned data set for the adherence analysis in terms of implementation and persistence. ConclusionsThe CleanADHdata.R script is a semiautomated procedure that increases standardization and reproducibility. This script has broader applicability within the realm of digital health, as it can be used to clean adherence data collected with diverse digital technologies.

BackgroundPsychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.MethodsBetween 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.ResultsA total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.ConclusionThe observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.

Background: Women may receive suboptimal pain management compared with men, and this disparity might be related to gender stereotypes. Objectives: To assess the influence of patient gender on the management of acute low back pain. Design: We assessed pain management by 231 physicians using an online clinical vignette describing a consultation for acute low back pain in a female or male patient. The vignette was followed by a questionnaire that assessed physicians’ management decisions and their gender stereotypes. Methods: We created an online clinical vignette presenting a patient with acute low back pain and assessed the influence of a patient’s gender on pain management. We investigated gender-related stereotyping regarding pain care by emergency physicians using the Gender Role Expectation of Pain questionnaire. Results: Both male and female physicians tended to consider that a typical man was more sensitive to pain, had less pain endurance, and was more willing to report pain than a typical woman. These stereotypes did not translate into significant differences in pain management between men and women. However, women tended to be referred less often for imaging examinations than men and were also prescribed lower doses of ibuprofen and opioids. The physician’s gender had a modest influence on management decisions, female physicians being more likely to prescribe ancillary examinations. Conclusion: We observed gender stereotypes among physicians. Our findings support the hypothesis that social characteristics attributed to men and women influence pain management. Prospective clinical studies are needed to provide a deeper understanding of gender stereotypes and their impact on clinical management.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention.Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases.Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons.Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated.Clinical Trial Registration:Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.

The COVID-19 pandemic that reached Europe in 2020 has often been compared to the Spanish flu pandemic of 1918. In this article, we compare the two pandemics in terms of their respective impacts on the loss of life expectancy at birth in six European countries (France, Italy, the Netherlands, Spain, Sweden, Switzerland) by estimating life expectancy in 2020 using Eurostat data. We found that the loss of life expectancy at birth was up to 20 times larger between 1917 and 1918 than between 2019 and 2020. A decomposition of these losses clearly shows that in all six countries, the main contributors were older age groups in 2020 and younger age groups in 1918. These observations are consistent with evidence indicating that most COVID-19 fatalities were among the elderly, while a majority of Spanish flu fatalities were among the young.

Abstract Background An interprofessional medication adherence intervention led by pharmacists, combining motivational interviews and feedback with electronic monitor (EM) drug assessment, was offered to all consecutive patients with diabetic kidney disease (DKD) (estimated glomerular filtration rate

ObjectiveDuring the COVID-19 pandemic, excess mortality has generally been estimated comparing overall mortality in a given year with either past mortality levels or past mortality trends, with different results. Our objective was to illustrate and compare the two approaches using mortality data for Switzerland in 2022, the third year of the COVID-19 pandemic.MethodsUsing data from the Swiss Federal Statistical Office, standardized mortality rates and life expectancies in 2022 were compared with those of the last pre-pandemic year 2019 (first approach), as well as with those that would be expected if the pre-pandemic downward trend in mortality had continued during the pandemic (second approach). The pre-pandemic trend was estimated via a Poisson log-linear model on age-specific mortality over the period 2010-19.ResultsUsing the first approach, we estimated in Switzerland in 2022 an excess mortality of 2.6% (95%CI: 1.0%-4.1%) for men and 2.5% (95%CI: 1.0%-4.0%) for women, while the excess mortality rose to 8.4% (95%CI: 6.9%-9.9%) for men and 6.0% (95%CI: 4.6%-7.5%) for women using the second approach. Age classes over 80 were the main responsible for the excess mortality in 2022 for both sexes using the first approach, although a significant excess mortality was also found in most age classes above 30 using the second approach. Life expectancy in 2022 has been reduced by 2.7 months for men and 2.4 months for women according to the first approach, whereas it was reduced by respectively 8.8 and 6.0 months according to the second approach.ConclusionsThe excess mortality and loss of life expectancy in Switzerland in 2022 are around three times greater if the pre-pandemic trend is taken into account than if we simply compare 2022 with 2019. These two different approaches, one being more speculative and the other more factual, can also be applied simultaneously and provide complementary results. In Switzerland, such a dual-approach strategy has shown that the pre-pandemic downward trend in mortality is currently halted, while pre-pandemic mortality levels have largely been recovered by 2022.

ObjectiveTo quantify the (direct and indirect) impacts of the COVID-19 pandemic on mortality for actual populations of persons living in 12 European countries in 2020.MethodBased on demographic and mortality data, as well as remaining life expectancies found in the Human Mortality Database, we calculated a “population life loss” in 2020 for men and women living in Belgium, Croatia, Denmark, Finland, Hungary, Lithuania, Luxembourg, Norway, Portugal, Spain, Sweden, and Switzerland. This quantity was obtained by dividing the total number of years lost in 2020 (estimated from all-cause mortality data and attributed directly or indirectly to COVID-19) by the size of the population.ResultsA significant population life loss was found in 8 countries in 2020, with men losing an average of 8.7, 5.0, 4.4, 4.0, 3.7, 3.4, 3.1, and 2.7 days in Lithuania, Spain, Belgium, Hungary, Croatia, Portugal, Switzerland, and Sweden, respectively. For women, this loss was 5.5, 4.3, 3.7, 3.7, 3.1, 2.4, 1.6, and 1.4 days, respectively. No significant losses were found in Finland, Luxembourg, Denmark and Norway. Life loss was highly dependent on age, reaching 40 days at the age of 90 in some countries, while only a few significant losses occurred under the age of 60. Even in countries with a significant population life loss in 2020, it was on average about 30 times lower than in 1918, at the time of the Spanish flu.ConclusionsOur results based on the concept of population life loss were consistent with those based on the classical concept of life expectancy, confirming the significant impact of COVID-19 on mortality in 8 European countries in 2020. However, while life expectancy losses were typically counted in months or years, population life losses could be counted in days, a potentially useful piece of information from a public health perspective.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation < 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level < 95% had a sensitivity of 69% and a negative likelihood ratio (LR−) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR− of 0.37. The addition of saturation < 95% to this CDR increased the sensitivity (96%) and decreased the LR− (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs.

Abstract The Fingolimod Patient Support Program (F-PSP) is an interprofessional specialty pharmacy service designed to ensure responsible use of fingolimod by promoting patient safety and medication adherence. This study aims to evaluate the safety and medication adherence of patients who joined the F-PSP between 2013 and 2016. Sociodemographic and medical characteristics, patient safety data (patient-reported symptoms, discontinuations due to adverse events (AEs), repeated first-dose monitoring), and medication adherence (implementation, persistence, reasons for discontinuation, influence of covariates, barriers and facilitators) were described. Sixty-seven patients joined the F-PSP. Patients reported a high frequency of symptoms. Due to AEs, 7 patients discontinued fingolimod, 3 took therapeutic breaks, and 1 reduced the regimen temporarily. Three patients repeated the first-dose monitoring. Patients had a high medication adherence over the 18-month analysis period: implementation decreased from 98.8 to 93.7%, and fingolimod persistence was 83.2% at 18 months. The patients’ level of education, professional situation, and living with child(ren) influenced implementation. Patients reported more facilitators of medication adherence than barriers. The F-PSP seems valuable for supporting individual patients (ensuring responsible use of fingolimod and inviting patients for shared-decision making) and public health (indirectly gathering real-world evidence).

Abstract Background Gender is an important social determinant, that influences healthcare. The lack of awareness on how gender influences health might lead to gender bias and can contribute to substandard patient care. Our objectives were to assess gender sensitivity and the presence of gender stereotypes among swiss medical students. Methods A validated scale (N-GAMS – Nijmegen Gender Awareness in Medicine Scale), with 3 subscores assessing gender sensitivity (GS) and gender stereotypes toward patients (GRIP) and doctors (GRID) (ranging from 1 to 5), was translated into French and was distributed to all medical students registered at the University of Lausanne, Switzerland in April–May 2017. Reliability of the three subscales was assessed calculating the alpha Cronbach coefficient. Mean subscales were calculated for male and female students and compared using two sample t-tests. A linear model was built with each subscale as a dependent variable and students’ sex and age as covariables. Results In total, 396 students answered the N-GAMS questionnaire, their mean age was 22 years old, 62.6% of them were women. GS and GRID sub-scores were not significantly different between female and male students (GS 3.62 for women, 3.70 for men, p = 0.27, GRID 2.10 for women, 2.13 for men, p = 0.76). A statistically significant difference was found in the GRIP subscale, with a mean score of 1.83 for women and 2.07 for men (p

Predicting the short-term evolution of the number of cancers is essential for planning investments and allocating health resources. The objective of this study was to predict the numbers of cancer cases and of the 12 most frequent cancer sites, and their age-standardized incidence rates, for the years 2019-2025 in Switzerland. Projections of the number of malignant cancer cases were obtained by combining data from two sources: forecasts of national age-standardized cancer incidence rates and population projections from the Swiss Federal Statistical Office. Age-standardized cancer incidence rates, approximating the individual cancer risk, were predicted by a low-order Autoregressive Integrated Moving Average (ARIMA) model. The contributions of changes in cancer risk (epidemiological component) and population aging and growth (demographic components) to the projected number of new cancer cases were each quantified. Between 2018 and 2025, age-standardized cancer incidence rates are predicted to stabilize for men and women at around 426 and 328/100,000, respectively (

ObjectiveTo analyze mortality trends in Switzerland in 2021, the second year of the COVID-19 pandemic.MethodsUsing data from the Swiss Federal Statistical Office, we compared mortality in Switzerland in 2021 with that of previous years in terms of standardized weekly deaths, standardized (annual) mortality rates (overall and stratified by age and sex) and life expectancy. The latter is a well-known demographic concept defining the average lifespan of a hypothetical cohort living and dying according to the mortality rates of a given year.ResultsAfter a favorable first half of the year and a fairly standard second half in terms of mortality in Switzerland, the year 2021 ended with a wave of deaths of moderate intensity related to the 5th wave of COVID-19. Overall, and after a notable increase in mortality in 2020 (+9.2%, 95%CI: +8.0%; +10.3%, compared to 2019, and +5.1%, 95%CI: +4.3%; +6.0%, compared to 2015-19), the pre-pandemic mortality level was approximately recovered in 2021 (+0.8%, 95%CI: -0.3%; +0.8%, compared to 2019, and -2.9%, 95%CI: -3.7%; -2.2%, compared to 2015-19). Life expectancy, after declining by 10 months for men and 6 months for women in 2020 (i.e. men would have lost 10 months and women 6 months had they lived their entire lives with COVID-19 as it was in 2020), returned in 2021 to 2019 levels for women (85.6 years) and regained 2018 levels for men (81.6 years, still -0.3 years from 2019). The age group responsible for the small remaining loss for men was the 50-70 age group, which had similar mortality in 2020 and 2021.ConclusionsThe second year of the COVID-19 pandemic in Switzerland was characterized by an approximate return to pre-pandemic mortality levels, with a faster recovery for women than for men with respect to 2020.

Background: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care. However, one-third of patients with low procalcitonin at baseline received antibiotics by day 28. Aim: To explore the factors associated with the overruling of initial procalcitonin guidance. Design and Setting: Secondary analysis of a cluster randomized trial in which patients with an LRTI were included. Method: Using the characteristics of patients, their disease, and general practitioners (GPs), we conducted a multivariate logistic regression, adjusted for clustering. Results: Ninety-five out of 301 (32%) patients with low procalcitonin received antibiotics by day 28. Factors associated with an overruling of procalcitonin guidance were: a history of chest pain (adjusted OR [aOR] 1.81, 95% confidence interval 1.03–3.17); a prescription of chest X-ray by the GP (aOR 4.65, 2.32–9.34); a C-reactive protein measured retrospectively above 100 mg/L (aOR 7.48, 2.34–23.93, reference ≤ 20 mg/L); the location of the GP practice in an urban setting (aOR 2.27, 1.18–4.37); and the GP’s number of years of experience (aOR per year 1.05, 1.01–1.09). Conclusions: Overruling of procalcitonin guidance was associated with GPs’ socio-demographic characteristics, pointing to the general behavioral problem of overprescription by physicians. Continuous medical education and communication training might support the successful implementation of procalcitonin point-of-care tests aimed at antibiotic stewardship.

BackgroundThe strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. ObjectiveThe aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. MethodsThe OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. ResultsThe first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. ConclusionsThe OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients’ needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. Trial RegistrationClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. International Registered Report Identifier (IRRID)DERR1-10.2196/30090

Abstract Background A minority of patients presenting with lower respiratory tract infection (LRTI) to their general practitioner (GP) have community-acquired pneumonia (CAP) and require antibiotic therapy. Identifying them is challenging, because of overlapping symptomatology and low diagnostic performance of chest X-ray. Procalcitonin (PCT) can be safely used to decide on antibiotic prescription in patients with LRTI. Lung ultrasound (LUS) is effective in detecting lung consolidation in pneumonia and might compensate for the lack of specificity of PCT. We hypothesize that combining PCT and LUS, available as point-of care tests (POCT), might reduce antibiotic prescription in LRTIs without impacting patient safety in the primary care setting. Methods This is a three-arm pragmatic cluster randomized controlled clinical trial. GPs are randomized either to PCT and LUS-guided antibiotic therapy or to PCT only-guided therapy or to usual care. Consecutive adult patients with an acute cough due to a respiratory infection will be screened and included if they present a clinical pneumonia as defined by European guidelines. Exclusion criteria are previous antibiotics for the current episode, working diagnosis of sinusitis, severe underlying lung disease, severe immunosuppression, hospital admission, pregnancy, inability to provide informed consent and unavailability of the GP. Patients will fill in a 28 day-symptom diary and will be contacted by phone on days 7 and 28. The primary outcome is the proportion of patients prescribed any antibiotic up to day 28. Secondary outcomes include clinical failure by day 7 (death, admission to hospital, absence of amelioration or worsening of relevant symptoms) and by day 28, duration of restricted daily activities, episode duration as defined by symptom score, number of medical visits, number of days with side effects due to antibiotics and a composite outcome combining death, admission to hospital and complications due to LRTI by day 28. An evaluation of the cost-effectiveness and of processes in the clinic using a mixed qualitative and quantitative approach will also be conducted. Discussion Our intervention targets only patients with clinically suspected CAP who have a higher pretest probability of definite pneumonia. The intervention will not substitute clinical assessment but completes it by introducing new easy-to-perform tests. Trial registration The study was registered on the 19th of June 2017 on the clinicaltrials.gov registry using reference number; NCT03191071.

Neutropenia is the most frequent dose-limiting toxicity reported in patients with metastatic breast cancer receiving palbociclib. The objective of this study was to investigate the pharmacokinetic–pharmacodynamic (PK/PD) relationships for toxicity (i.e., absolute neutrophil count, ANC) and efficacy (i.e., progression-free survival, PFS). A semi-mechanistic PK/PD model was used to predict neutrophils’ time course using a population approach (NONMEM). Influence of demographic and clinical characteristics was evaluated. Cox proportional hazards models were developed to evaluate the influence of palbociclib PK on PFS. A two-compartment model with first-order absorption and a lag time adequately described the 255 palbociclib concentrations provided by 44 patients. The effect of the co-administration of proton-pump inhibitors in fasting conditions increased palbociclib clearance by 56%. None of the tested covariates affected the PD parameters. Model-based simulations confirmed the concentration-dependent and non-cumulative properties of palbociclib-induced neutropenia, reversible after treatment withdrawal. The ANC nadir occurred approximately at day 24 of each cycle. Cox analyses revealed a trend for better PFS with increasing palbociclib exposure in older patients. By characterizing palbociclib-induced neutropenia, this model offers support to clinicians to rationally optimize treatment management through patient-individualized strategies.

ObjectiveTo estimate the basic reproduction number (R0) for COVID-19 in Western Europe.MethodsData (official statistics) on the cumulative incidence of COVID-19 at the start of the outbreak (before any confinement rules were declared) were retrieved in the 15 largest countries in Western Europe, allowing us to estimate the exponential growth rate of the disease. The rate was then combined with estimates of the distribution of the generation interval as reconstructed from the literature.ResultsDespite the possible unreliability of some official statistics about COVID-19, the spread of the disease appears to be remarkably similar in most European countries, allowing us to estimate an average R0 in Western Europe of 2.2 (95% CI: 1.9-2.6).ConclusionsThe value of R0 for COVID-19 in Western Europe appears to be significantly lower than that in China. The proportion of immune persons in the European population required to stop the outbreak could thus be closer to 50% than to 70%.

ObjectiveTo quantify excess all-cause mortality in Switzerland in 2020, a key indicator for assessing direct and indirect consequences of the COVID-19 pandemic.MethodsUsing official data on deaths in Switzerland, all-cause mortality in 2020 was compared with that of previous years using directly standardized mortality rates, age- and sex-specific mortality rates, and life expectancy.ResultsThe standardized mortality rate was 8.8% higher in 2020 than in 2019, returning to the level observed 5-6 years before, around the year 2015. This increase was greater for men (10.6%) than for women (7.2%) and was statistically significant only for men over 70 years of age, and for women over 75 years of age. The decrease in life expectancy in 2020 compared to 2019 was 0.7%, with a loss of 9.7 months for men and 5.3 months for women.ConclusionsThere was an excess mortality in Switzerland in 2020, linked to the COVID-19 pandemic. However, as this excess only concerned the elderly, the resulting loss of life expectancy was restricted to a few months, bringing the mortality level back to 2015.

BackgroundHazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.MethodsThe Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively.ResultsMost participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P ConclusionsIn this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.

Introduction Few studies have assessed the efficacy of smoking cessation interventions in individuals with type 2 diabetes, but interventions adapted to the specific needs of this population are warranted. The aim of this study is to assess the efficacy of a smoking cessation intervention in a population of smokers with type 2 diabetes and to measure the metabolic impact of smoking cessation.Methods and analysis The study is an open-label, randomised control trial. Participants recruited from a sanitary region of Switzerland will be randomly allocated to either the intervention or the control arm. The intervention group will have four individual counselling sessions over 12 weeks. Trained research nurses will conduct the behavioural intervention, using motivational interviews and addressing diabetes and gender specificities. The control group will have one short counselling session at baseline and will be given written information on smoking cessation. Both groups will have a follow-up visit at 26 and 52 weeks. Demographic and medical data will be collected at baseline and follow-up, along with blood and urine samples. The primary study outcome is continuous smoking abstinence validated by expired-air carbon monoxide from week 12 to week 52. Secondary study outcomes are continuous and 7-day point prevalence smoking abstinence at 12 and 26 weeks; change in motivation to quit and cigarette consumption; and change in glycosylated haemoglobin levels, body weight, waist circumference and renal function after smoking cessation. In a subsample of 80 participants, change in stool microbiota from baseline will be measured at 3, 8 and 26 weeks after smoking cessation.Ethics and dissemination Ethical approval has been obtained by the competent ethics committee (Commission cantonale d’éthique de la recherche sur l’être humain, CER-VD 2017–00812). The results of the study will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration numbers ClinicalTrials.gov NCT03426423 and SNCTP000002762; Pre-results.

BackgroundMedical decision-making relies partly on the probability of disease. Current recommendations for the management of common diseases are based increasingly on scores that use arbitrary probability thresholds.ObjectiveTo assess decision-making in pharyngitis and appendicitis using a set of clinical vignettes, and the extent to which management is congruent with the true probability of having the disease.DesignWe developed twenty-four clinical vignettes with clinical presentations corresponding to specific probabilities of having disease defined by McIsaac (pharyngitis) or Alvarado (appendicitis) scores. Each participant answered four randomly selected web-based vignettes.ParticipantsGeneral practitioners (GP) working in primary care structures in Switzerland and the USA.Main measuresA comparison between the GP's management decision according to the true probability of having the disease and to the GP's estimated probability, investigating the GP's ability to estimate probability of disease.Key resultsThe mean age of the GPs was 48 years (SD 12) and 66% were men. The correlation between the GP's clinical management decision based on the vignette and the recommendations was stronger for appendicitis than pharyngitis (kw = 0.74, 95% CI 0.70-0.78 vs. kw = 0.66, 95% CI 0.62-0.71). On the other hand, the association between the clinical management decision and the probability of disease estimated by GPs was more congruent with recommendations for pharyngitis than appendicitis (kw = 0.70, 95% CI 0.66-0.73 vs. 0.61, 95% CI 0.56-0.66). Only a minority of GPs correctly estimated the probability of disease (29% for appendicitis and 39% for pharyngitis).ConclusionsDespite the fact that general practitioners often misestimate the probability of disease, their management decisions are usually in line with recommendations. This means that they use other approaches, perhaps more subjective, to make decisions, such as clinical judgment or reasoning that integrate factors other than just the risk of the disease.

Abstract Background Geriatric syndromes are rarely detected in family medicine. Within the AGE program (active geriatric evaluation), a brief assessment tool (BAT) designed for family physicians (FP) was developed and its diagnostic performance estimated by comparison to a comprehensive geriatric assessment. Methods This prospective diagnostic study was conducted in four primary care sites in Switzerland. Participants were aged at least 70 years and attending a routine appointment with their physician, without previous documented geriatric assessment. Participants were assessed by their family physicians using the BAT, and by a geriatriciant who performed a comprehensive geriatric assessment within the following two-month period (reference standard). Both the BAT and the full assessment targeted eight geriatric syndromes: cognitive impairment, mood impairment, urinary incontinence, visual impairment, hearing loss, undernutrition, osteoporosis and gait and balance impairment. Diagnostic accuracy of the BAT was estimated in terms of sensitivity, specificity, and predictive values; secondary outcomes were measures of feasibility, in terms of added consultation time and comprehensiveness in applying the BAT items. Results Prevalence of the geriatric syndromes in participants (N=85, 46 (54.1%) women, mean age 78 years (SD 6))ranged from 30.0% (malnutrition and cognitive impairment) to 71.0% (visual impairment), with a median number of 3 syndromes (IQR 2 to 4) per participant. Sensitivity of the BAT ranged from 25.0% for undernutrition (95%CI 9.8% - 46.7%) to 82.1% for hearing impairment (95%CI 66.5% - 92.5%), while specificity ranged from 45.8% for visual impairment (95%CI 25.6–67.2) to 87.7% for undernutrition (76.3% to 94.9%). Finally, most negative predictive values (NPV) were between 73.5% and 84.1%, excluding visual impairment with a NPV of 50.0%. Family physicians reported BAT use as per instructions for 76.7% of the syndromes assessed. Conclusions Although the BAT does not replace a comprehensive geriatric assessment, it is a useful and appropriate tool for the FP to screen elderly patients for most geriatric syndromes. Trial registration The study was registered on ClinicalTrials.gov on February 20, 2013 (NCT01816087).

Abstract Background The criteria for defining severe malaria have evolved over the last 20 years. We aimed to assess the strength of association of death with features currently characterizing severe malaria through a systematic review and meta-analysis. Method Electronic databases (Medline, Embase, Cochrane Database of Systematic Reviews, Thomson Reuters Web of Knowledge) were searched to identify publications including African children with severe malaria. PRISMA guidelines were followed. Selection was based on design (epidemiological, clinical and treatment studies), setting (Africa), participants (children 2. Features with the lowest pooled ORs were impaired consciousness (0.58, 95% CI 0.25–1.37), severe anemia (0.76, 95% CI 0.5– 1.13), and prostration (1.12, 95% CI 0.45–2.82). Conclusion The findings of this meta-analysis show that the strength of association between the criteria defining severe malaria and death is quite variable for each clinical and/or laboratory feature (OR ranging from 0.58 to 5.96). This ranking allowed the identification of features weakly associated with death, such as impaired consciousness and prostration, which could assist to improve case definition, and thus optimize antimalarial treatment.

Abstract Background The present study takes place within a geriatric program, aiming at improving the diagnosis and management of geriatric syndromes in primary care. Within this program it was of prime importance to be able to rely on a robust and reproducible geriatric consultation to use as a gold standard for evaluating a primary care brief assessment tool. The specific objective of the present study was thus assessing the agreement and reliability of a comprehensive geriatric consultation. Method The study was conducted at the outpatient clinic of the Service of Geriatric Medicine, University of Lausanne, Switzerland. All community-dwelling older persons aged 70 years and above were eligible. Patients were excluded if they hadn’t a primary care physician, they were unable to speak French, or they were already assessed by a geriatrician within the last 12 months. A set of 9 geriatricians evaluated 20 patients. Each patient was assessed twice within a 2-month delay. Geriatric consultations were based on a structured evaluation process, leading to rating the following geriatric conditions: functional, cognitive, visual, and hearing impairment, mood disorders, risk of fall, osteoporosis, malnutrition, and urinary incontinence. Reliability and agreement estimates on each of these items were obtained using a three-way Intraclass Correlation and a three-way Observed Disagreement index. The latter allowed a decomposition of overall disagreement into disagreements due to each source of error variability (visit, rater and random). Results Agreement ranged between 0.62 and 0.85. For most domains, geriatrician-related error variability explained an important proportion of disagreement. Reliability ranged between 0 and 0.8. It was poor/moderate for visual impairment, malnutrition and risk of fall, and good/excellent for functional/cognitive/hearing impairment, osteoporosis, incontinence and mood disorders. Conclusions Six out of nine items of the geriatric consultation described in this study (functional/cognitive/hearing impairment, osteoporosis, incontinence and mood disorders) present a good to excellent reliability and can safely be used as a reference (gold standard) to evaluate the diagnostic performance of a primary care brief assessment tool. More objective/significant measures are needed to improve reliability of malnutrition, visual impairment, and risk of fall assessment before they can serve as a safe gold standard of a primary care tool.

AIM OF THE STUDY Although physicians’ home visits are highly valued by patients, and are among the measures that contribute to maintaining elderly patients at home, their number is decreasing worldwide. We aimed to describe the trends in home visits made by general practitioners (GPs) in the canton of Vaud in Switzerland between 2006 and 2015, and to explore their associated characteristics. METHODS We retrospectively analysed billing data from family physicians (internists, generalists and practicing physicians) transmitted to the cantonal trust centre between 2006 and 2015. We explored physician and patient characteristics, first over the entire 10-year study period and then averaged by year. To explore factors associated with the number of home visits, we fitted a mixed effect negative binomial regression of the annual number of home visits per physician. RESULTS Over ten years, 631 physicians billed a total of 451,634 home visits, of which 19.8% (n = 89,966) were emergency visits, and 9.7% (n = 43,915) were over the weekend. Home visits represented 2.5% of all consultations. Although the average annual number of physicians doing home visits remained stable at around 400, the mean annual number of visits per physician decreased from 125 in 2006 to 75 in 2015, resulting in a 40% decline in the absolute number of visits. Male physicians undertook more home visits than their female counterparts did, although the difference diminished over time. Visits to elderly patients (65+) represented 84.2% of the home visits. CONCLUSIONS Although most physicians in the canton of Vaud continue to visit patients at home, the overall number of home visits is declining. Most home visits consist of routine visits to elderly patients. Physicians’ gender, age and specialty are associated with the number of home visits. In the rapidly evolving context of an ageing population and the development of home care, physicians’ role in home care provision should be revised, taking into account patient expectations and current health system constraints.

ObjectiveThis secondary analysis of data of a randomized controlled trial (RCT) retrospectively investigated the performance of pulse oximetry in identifying children with severe illnesses, with and without respiratory signs/symptoms, in a cohort of children followed for morbid episodes in an intervention trial assessing the efficacy of Intermittent Preventive Treatment for malaria in infants (IPTi) in Papua New Guinea (PNG) from June 2006 to May 2010.SettingThe IPTi study was conducted in a paediatric population visiting two health centres on the north coast of PNG in the Mugil area of the Sumkar District.ParticipantsA total of 669 children visited the clinic and a total of 1921 illness episodes were recorded. Inclusion criteria were: age between 3 and 27 months, full clinical record (signs/symptoms) and pulse oximetry used systematically to assess sick children at all visits. Children were excluded if they visited the clinic in the previous 14 days.OutcomesThe outcome measures were severe illness, severe pneumonia, pneumonia, defined by the Integrated Management of Childhood Illness (IMCI) definitions, and hospitalization.ResultsOut of 1921 illness episodes, 1663 fulfilled the inclusion criteria. A total of 139 severe illnesses were identified, of which 93 were severe pneumonia. The ROC curves of pulse oximetry (continuous variable) showed an AUC of 0.63, 0.68 and 0.65 for prediction of severe illness, severe pneumonia and hospitalization, respectively. Pulse oximetry allowed better discrimination between severe and non-severe illness, severe and non-severe pneumonia, admitted and non-admitted patients, in children ≤12-months of age relative to older patients. For the threshold of peripheral arterial oxygen saturation ≤ 94% measured by pulse oximetry (SpO2), unadjusted odds ratios for severe illness, severe pneumonia and hospitalization were 6.1 (95% Confidence Interval (CI) 3.9-9.8), 8.5 (4.9-14.6) and 5.9 (3.4-10.3), respectively.ConclusionPulse oximetry was helpful in identifying children with severe illness in outpatient facilities in PNG. A SpO2 of 94% seems the most discriminative threshold. Considering its affordability and ease of use, pulse oximetry could be a valuable additional tool assisting the decision to admit for treatment.

Purpose: This study aims to describe a 12-month medication adherence with oral anticancer medications (OAMs) in a routine care medication adherence program, and to better characterize non-persistence.Patients and methods:In this observational, one-centered, longitudinal study, medication adherence was monitored electronically while patients were taking part in a medication adherence program for 12 months or until treatment stop. Patients were >18 years and starting or taking one of the following OAMs: letrozole, exemestane, imatinib, sunitinib, capecitabine, or temozolomide. Non-persistence was defined as any premature treatment interruption due to patient's unilateral decision or to a medical decision because of adverse effects. The Kaplan Meier survival function estimate was used to characterize persistence, and Generalized Estimating Equations (GEE) were adopted to fit implementation. Statistical analyses were performed using the R software package.Results: Forty-three outpatients with various tumor entities were enrolled. Reasons for quitting the medication adherence program and/or OAM medication were characterized as OAM discontinuation due to adverse effects or toxicity (n = 5), planned OAM completion time (n = 10), OAM failure (cancer relapse) (n = 5) and non-compliance to the adherence program (n = 3). In persistent patients, the implementation rates were high (from 98% at baseline to 97% at 12 months). The probability of being persistent at 12 months was estimated at 85%.Conclusion: A better characterization of both persistence and implementation to OAMs in real life settings is crucial for understanding and optimizing medication adherence to OAMs. The complex identification of non-persistence underlines the need to carefully and prospectively assess OAM interruption or treatment switch reasons. The GEE analysis for describing implementation to OAMs will allow researchers and professionals to take advantage of the richness of longitudinal real-time data, to avoid reducing such data through thresholds and to put them into perspective with OAM blood levels.

Objective: Cardiovascular diseases (CVD) are the main cause of death worldwide and despite a higher prevalence in men, mortality from CVD is higher among women. Few studies have assessed sex differences in chest pain management in ambulatory care. The objective of this post hoc analysis of data from a prospective cohort study was to assess sex differences in the management of chest pain in ambulatory care. Setting: We used data from the Thoracic Pain in Community cohort study that was realized in 58 primary care practices and one university ambulatory clinic in Switzerland. Participants: In total, 672 consecutive patients aged over 16 years attending a primary care practice or ambulatory care clinic with a complaint of chest pain were included between February and June 2001. Their mean age was 55.2 years and 52.5% were women. Main outcome measures: The main outcome was the proportion of patients referred to a cardiologist at 12 months follow-up. A panel of primary care physicians assessed the final diagnosis retained for chest pain at 12 months. Results: The prevalence of chest pain of cardiovascular origin (n = 108, 16.1%) was similar for men and women (17.5% vs 14.8%, respectively, p = 0.4). Men with chest pain were 2.5 times more likely to be referred to a cardiologist than women (16.6% vs 7.4%, odds ratio: 2.49, 95% confidence interval: 1.52–4.09). After adjustment for the patients’ age and cardiovascular disease risk factors, the estimates did not significantly change (odds ratio: 2.30, 95% confidence interval: 1.30–3.78). Conclusion: Although the same proportion of women and men present with a chest pain of cardiovascular origin in ambulatory care, there is a strong sex bias in their management. These data suggest that effort must be made to assure equity between men and women in medical care.

Three correlated frailty models are used to analyze bivariate timeto- event data by assuming gamma, log-normal and compound Poisson distributed frailty. All approaches allow to deal with right censored lifetime data and account for heterogeneity as well as for a non-susceptible (cure) fraction in the study population. In the gamma and compound Poisson model traditional ML estimation methods are used, whereas in the log-normal model MCMC methods are applied. Breast cancer incidence data of Swedish twin pairs illustrate the practical relevance of the models, which are used to estimate the size of the susceptible fraction and the correlation between the frailties of the twin partners. We discuss future directions of development of the methods and additional thoughts concerning their advantages and use.

Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS.Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization.During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS.The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.