[Is mortality an objective indicator for measuring the impact of an epidemic?: The example of Covid-19 in Switzerland]. / La mortalité est-elle un indicateur objectif pour mesurer l'impact d'une épidémie ?. L'exemple du Covid-19 en Suisse.

Measuring the health impact of an epidemic using appropriate indicators is necessarily complex. Mortality does not sum up all the issues, but at least it seems to be an objective indicator. There are, however, a number of different mortality indicators, which do not all convey the same message. During the Covid-19 epidemic in Switzerland, the mortality rate rose by 10.2% in 2020, while life expectancy fell by "only" 0.8%, or 8.3 months, a decline described as "modest" or "complete freefall" depending on when it was published. In reality, the population living in Switzerland in 2020 lost an average of "only" 2.4 days, as the epidemic did not last their entire lives. The use of such an indicator, in comparison with losses due to other factors, would enable us to better estimate the real impact of an epidemic.

Mesurer l'impact sanitaire d'une épidémie à l'aide d'indicateurs appropriés est forcément complexe. La mortalité ne résume pas tous les enjeux mais semble au moins être un indicateur objectif. Il existe cependant différents indicateurs de mortalité ne donnant pas tous le même message. Lors de l'épidémie de Covid-19 en Suisse, le taux de mortalité a augmenté de 10,2 % en 2020, alors que l'espérance de vie n'a diminué « que ¼ de 0,8 %, ou 8,3 mois, recul par ailleurs qualifié de « modeste ¼ ou de « chute libre ¼ selon quand il a été publié. En réalité, la population vivant en Suisse en 2020 n'a perdu en moyenne « que ¼ 2,4 jours car l'épidémie n'a pas duré toute sa vie. L'utilisation d'un tel indicateur, en comparaison avec les pertes dues à d'autres facteurs, permettrait une meilleure estimation de l'impact réel d'une épidémie.

Estimation of adherence to medication treatment in presence of censoring.

AIMS: The purpose of this study is to provide a theoretical framework for the analysis of medication adherence based on longitudinal data from electronic medication monitors and to suggest methods for unbiased estimation of the effect of time and covariates on adherence. METHODS: After defining the statistical summaries involved in adherence analyses and the assumptions necessary for their estimation, we address the issue of bias encountered when adherence is estimated on censored data. We suggest 2 unbiased methods to estimate adherence: (i) indirect combining implementation and persistence; and (ii) based on weights, allowing estimation of the effect of time and covariates on adherence via generalized estimating equations models. RESULTS: We applied the proposed methods to investigate the effect of sex on adherence in a sample of 43 oncology patients followed 1 year. Implementation was higher for men than for women at baseline (98.8 vs. 97.5%, odds ratio [OR] 2.08, 95% confidence interval [CI]: 1.00-4.35), whereas the relationship was reversed at 1 year (94.5 vs. 96.4%, OR 0.65, 95%CI: 0.28-1.52). Adherence declined faster in men, with year-end values of 46.3% for men and 92.2% for women (OR 0.07, 95%CI: 0.02-0.26). CONCLUSION: Estimation of adherence is a complex statistical issue with longitudinal and duration data, possibly censored, interleaving. This study provides a theoretical framework and suggests methods for unbiased estimation of adherence as a function of time and covariates. This allows the effect of an intervention to be estimated in clinical trials, and helps healthcare providers reframe adherence programmes to address covariates such as sex.

Effectiveness of an Interprofessional Program (Siscare) for Supporting Patients With Type 2 Diabetes.

Objective: To assess the effectiveness of an interprofessional support program (Siscare) that includes motivational interviews (patient-pharmacist), electronic monitoring (EM) of medications, patient-reported and clinical outcomes monitoring, and interactions with physicians for patients with type 2 diabetes in French-speaking Switzerland. Methods: This was a prospective, multicenter, observational cohort study using a hybrid implementation-effectiveness design. Individual daily adherence to at least one oral antidiabetic medication was measured by EM. A global adherence score was estimated by the product of a model-estimated implementation and a nonparametric estimate of persistence over time. Clinical outcomes (A1C, blood glucose, BMI, blood pressure, heart rate, and cholesterol levels) and quality of life (QoL) were analyzed over time using linear mixed-effect models. Results: A total of 212 patients were included from 27 pharmacies; 120 patients (57%) were followed up for at least 15 months. In total, 140 patients (66%) were male, the mean age was 64 ± 11 years, and the mean number of chronic medications per patient at baseline was 5 ± 3. Of 178 patients who used EM, 95% (95% CI 92-99%) remained persistent at the end of the follow-up period. The percentage of persistent patients taking their medications appropriately (implementation) was stable during follow-up and was estimated to be 90% (95% CI 87-92%) at baseline and 88% (95% CI 84-91%) at month 15. At baseline, the mean A1C and BMI were 7.5% and 31 kg/m2, respectively, which decreased by 0.5% (P = 0.012) and 0.6 kg/m2 (P = 0.017), respectively, after 15 months. QoL remained stable during follow-up. Conclusion: The program supports medication adherence and improves clinical outcomes, illustrating the overall preventive effect of coordinated care.

Comparison of statistical models to predict age-standardized cancer incidence in Switzerland.

This study compares the performance of statistical methods for predicting age-standardized cancer incidence, including Poisson generalized linear models, age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) models, autoregressive integrated moving average (ARIMA) time series, and simple linear models. The methods are evaluated via leave-future-out cross-validation, and performance is assessed using the normalized root mean square error, interval score, and coverage of prediction intervals. Methods were applied to cancer incidence from the three Swiss cancer registries of Geneva, Neuchatel, and Vaud combined, considering the five most frequent cancer sites: breast, colorectal, lung, prostate, and skin melanoma and bringing all other sites together in a final group. Best overall performance was achieved by ARIMA models, followed by linear regression models. Prediction methods based on model selection using the Akaike information criterion resulted in overfitting. The widely used APC and BAPC models were found to be suboptimal for prediction, particularly in the case of a trend reversal in incidence, as it was observed for prostate cancer. In general, we do not recommend predicting cancer incidence for periods far into the future but rather updating predictions regularly.

Use of standardized brief geriatric evaluation compared with routine care in general practice for preventing functional decline: a pragmatic cluster-randomized trial.

BACKGROUND: Although assessment of geriatric syndromes is increasingly encouraged in older adults, little evidence exists to support its systematic use by general practitioners (GPs). The aim of this study was to determine whether a systematic geriatric evaluation performed by GPs can prevent functional decline. METHODS: We conducted a controlled, open-label, pragmatic cluster-randomized trial in 42 general practices in Switzerland. Participating GPs were expected to enrol an average of 10 community-dwelling adults (aged ≥ 75 yr) who understood French, and had visited their GP at least twice in the previous year. The intervention consisted of yearly assessment by the GP of 8 geriatric syndromes with an associated tailored management plan according to assessment results, compared with routine care. Our primary outcomes were the proportion of patients who lost at least 1 instrumental activity of daily living (ADL) and the proportion who lost at least 1 basic ADL, over 2 years. Our secondary outcomes were quality-of-life scores, measured using the older adult module of the World Health Organization Quality of Life Instrument, and health care use. RESULTS: Forty-two GPs recruited 429 participants (63% women) with a mean age of 82.5 years (standard deviation 4.8 yr) at time of recruitment. Of these, we randomly assigned 217 participants to the intervention and 212 to the control arm. The proportion of patients who lost at least 1 instrumental ADL in the intervention and control arms during the course of the study was 43.6% and 47.6%, respectively (risk difference -4.0%, 95% confidence interval [CI] -14.9% to 6.7%, p = 0.5). The proportion of patients who lost at least 1 basic ADL was 12.4% in the intervention arm and 16.9% in the control arm (risk difference -5.1%, 95% CI -14.3% to 4.1%, p = 0.3). INTERPRETATION: A yearly geriatric evaluation with an associated management plan, conducted systematically in GP practices, does not significantly lessen functional decline among community-dwelling, older adult patients, compared with routine care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02618291.

Gender awareness among medical students in a Swiss University.

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 < 0.001), which suggests a more gender stereotyped opinion toward patients among male students. A trend was observed with age, gender sensibility increased (p < 0.001) and stereotypes decreased (GRIP p = 0.04, GRID p = 0.02) with students getting older. CONCLUSION: Medical students' gender sensitivity seems to improve throughout the medical curriculum, and women students have less stereotypes towards patients than men do. The implementation of a gender-sensitive teaching in the medical curriculum could improve students' knowledge, limit gender bias and improve patients' care.

Procalcitonin and lung ultrasonography point-of-care testing to decide on antibiotic prescription in patients with lower respiratory tract infection in primary care: protocol of a pragmatic cluster randomized trial.

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 .

Performance of a brief geriatric evaluation compared to a comprehensive geriatric assessment for detection of geriatric syndromes in family medicine: a prospective diagnostic study.

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 ).

Clinical and laboratory predictors of death in African children with features of severe malaria: a systematic review and meta-analysis.

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 < 15 years old with severe malaria), outcome (survival/death rate), and prognostic indicators (clinical and laboratory features). Quality assessment was performed following the criteria of the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Odds ratios (ORs) were calculated for each study and prognostic indicator, and, when a test was assessed in at least two studies, pooled estimates of ORs were computed using fixed- or random-effects meta-analysis. RESULTS: A total of 601 articles were identified and screened and 30 publications were retained. Features with the highest pooled ORs were renal failure (5.96, 95% CI 2.93-12.11), coma score (4.83, 95% CI 3.11-7.5), hypoglycemia (4.59, 95% CI 2.68-7.89), shock (4.31, 95% CI 2.15-8.64), and deep breathing (3.8, 95% CI 3.29-4.39). Only half of the criteria had an OR > 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.

A prospective study assessing agreement and reliability of a geriatric evaluation.

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.

Does This Patient Have Acute Mountain Sickness?: The Rational Clinical Examination Systematic Review.

Importance: Acute mountain sickness (AMS) affects more than 25% of individuals ascending to 3500 m (11 500 ft) and more than 50% of those above 6000 m (19 700 ft). AMS may progress from nonspecific symptoms to life-threatening high-altitude cerebral edema in less than 1% of patients. It is not clear how to best diagnose AMS. Objective: To systematically review studies assessing the accuracy of AMS diagnostic instruments, including the visual analog scale (VAS) score, which quantifies the overall feeling of sickness at altitude (VAS[O]; various thresholds), Acute Mountain Sickness-Cerebral score (AMS-C; ≥0.7 indicates AMS), and the clinical functional score (CFS; ≥2 indicates AMS) compared with the Lake Louise Questionnaire Score (LLQS; score of ≥5). Data Extraction and Synthesis: Searches of MEDLINE and EMBASE from inception to May 2017 identified 1245 publications of which 91 were suitable for prevalence analysis (66 944 participants) and 14 compared at least 2 instruments (1858 participants) using a score of 5 or greater on the LLQS as a reference standard. To determine the prevalence of AMS for establishing the pretest probability of AMS, a random-effects meta-regression was performed based on the reported prevalence of AMS as a function of altitude. Main Outcomes and Measures: AMS prevalence, likelihood ratios (LRs), sensitivity, and specificity of screening instruments. Results: The final analysis included 91 articles (comprising 66 944 study participants). Altitude predicted AMS and accounted for 28% of heterogeneity between studies. For each 1000-m (3300-ft) increase in altitude above 2500 m (8200 ft), AMS prevalence increased 13% (95% CI, 9.5%-17%). Testing characteristics were similar for VAS(O), AMS-C, and CFS vs a score of 5 or greater on the LLQS (positive LRs: range, 3.2-8.2; P = .22 for comparisons; specificity range, 67%-92%; negative LRs: range, 0.30-0.36; P = .50 for comparisons; sensitivity range, 67%-82%). The CFS asks a single question: "overall if you had any symptoms, how did they affect your activity (ordinal scale 0-3)?" For CFS, moderate to severe reduction in daily activities had a positive LR of 3.2 (95% CI, 1.4-7.2) and specificity of 67% (95% CI, 37%-97%); no reduction to mild reduction in activities had a negative LR of 0.30 (95% CI, 0.22-0.39) and sensitivity of 82% (95% CI, 77%-87%). Conclusions and Relevance: The prevalence of acute mountain sickness increases with higher altitudes. The visual analog scale for the overall feeling of sickness at altitude, Acute Mountain Sickness-Cerebral, and clinical functional score perform similarly to the Lake Louise Questionnaire Score using a score of 5 or greater as a reference standard. In clinical and travel settings, the clinical functional score is the simplest instrument to use. Clinicians evaluating high-altitude travelers who report moderate to severe limitations in activities of daily living (clinical functional score ≥2) should use the Lake Louise Questionnaire Score to assess the severity of acute mountain sickness.

Determining clinical decision thresholds for HIV-positive patients suspected of having tuberculosis.

Clinical decision thresholds may aid the evaluation of diagnostic tests but have rarely been determined for tuberculosis (TB). We presented clinicians with six web-based clinical scenarios, describing patients with HIV and possible TB at various sites and with a range of clinical stability. The probability of disease was varied randomly and clinicians asked to make treatment decisions; threshold curves and therapeutic thresholds were calculated. Test and treatment thresholds were calculated using Bayes theorem and the diagnostic accuracy of Xpert MTB/RIF. We received 165 replies to our survey. Therapeutic thresholds vary depending on the clinical stability and site of suspected disease. For inpatients, it ranges from 3.4% in unstable to 79.6% in stable patients. For TB meningitis, it ranges from 0% in unstable to 51.4% in stable patients and for pulmonary TB in outpatients it ranges from 29.1% in unstable to 74.5% in the stable patients. Test and treatment thresholds vary in a similar way with test thresholds ranging from 0 in unstable patients with suspected meningitis to 8.2% for stable inpatients. Treatment thresholds vary from 0 for unstable patients with suspected meningitis to 97% for stable inpatients. Therapeutic thresholds for TB can be determined by presenting clinicians with patient scenarios with random probabilities of disease and can be used to calculate test and treatment thresholds using Bayes theorem. Thresholds are lower when patients are more clinically unstable and when the implications of inappropriately withholding therapy are more serious. These results can be used to improve use and evaluation of diagnostic tests.

Clinical decision making : from theory to practice and backward. / Raisonnement clinique : de la théorie à la pratique et retour.

Being able to analyze all the successive steps of decision making from the first contact with the patient to the final diagnosis is complex because it refers sometimes to intuitive elements proper to each clinician. However, understanding how they integrate probabilities of diseases into their clinical practice and manage diagnostic uncertainties is crucial. This allows a more rational practice of medicine and identifying factors related to the patient, physician or context that may modify the clinical decision making. Furthermore, the use of tools such as clinical scores has taken an important place with the evidence based medicine. Given the fact that they are partly theoretical, it is necessary to assess whether these recommendations are in line with clinical practice.

Pouvoir analyser toutes les étapes successives de raisonnement intervenant depuis le premier contact avec le patient jusqu'au diagnostic final est complexe car cela fait appel à des éléments parfois intuitifs, propres à chaque praticien. Cependant, comprendre comment ces derniers intègrent dans leur pratique les probabilités de maladies et gèrent les incertitudes diagnostiques est crucial. Cela permet d'avoir une approche plus rationnelle de la médecine et d'identifier les facteurs liés au patient, au médecin ou au contexte pouvant intervenir dans une prise en charge médicale. Avec la pratique basée sur les preuves, l'utilisation d'outils tels que les scores cliniques a pris une place importante dans le raisonnement clinique. Compte tenu du côté quelque peu arbitraire de ces outils, il est nécessaire d'évaluer si les recommandations sont en adéquation avec la pratique clinique.

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers.

INTRODUCTION: The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. METHODS: In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. RESULTS: Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 µm (95% confidence interval [CI]: 1082-1287) and increased by 93 µm (95% CI: 25-161) and 108 µm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 µm per each 10-mmHg raise in SBP at 1 year and an increase of 39 µm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. CONCLUSION: Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. IMPLICATIONS: Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. Our findings emphasize the importance of focusing not only on smoking cessation among smokers, but to simultaneously control other CVRFs, particularly blood pressure, in order to prevent future cardiovascular disease.

Assessing interrater agreement on binary measurements via intraclass odds ratio.

Interrater agreement on binary measurements is usually assessed via Scott's π or Cohen's κ, which are known to be difficult to interpret. One reason for this difficulty is that these coefficients can be defined as a correlation between two exchangeable measurements made on the same subject, that is as an "intraclass correlation", a concept originally defined for continuous measurements. To measure an association between two binary variables, it is however more common to calculate an odds ratio rather than a correlation. For assessing interrater agreement on binary measurements, we suggest thus to calculate the odds ratio between two exchangeable measurements made on the same subject, yielding the concept of "intraclass odds ratio". Since it is interpretable as a ratio of probabilities of (strict) concordance and discordance (between two raters rating two subjects), an intraclass odds ratio might be easier to understand for researchers and clinicians than an intraclass correlation. It might thus be a valuable descriptive measure (summary index) to evaluate the agreement among a set of raters, without having to refer to arbitrary benchmark values. To facilitate its use, an explicit formula to calculate a confidence interval for the intraclass odds ratio is also provided.

A novel approach to the determination of clinical decision thresholds.

Our objective was to determine the test and treatment thresholds for common acute primary care conditions. We presented 200 clinicians with a series of web-based clinical vignettes, describing patients with possible influenza, acute coronary syndrome (ACS), pneumonia, deep vein thrombosis (DVT) and urinary tract infection (UTI). We randomly varied the probability of disease and asked whether the clinician wanted to rule out disease, order tests or rule in disease. By randomly varying the probability, we obtained clinical decisions across a broad range of disease probabilities that we used to create threshold curves. For influenza, the test (4.5% vs 32%, p<0.001) and treatment (55% vs 68%, p=0.11) thresholds were lower for US compared with Swiss physicians. US physicians had somewhat higher test (3.8% vs 0.7%, p=0.107) and treatment (76% vs 58%, p=0.005) thresholds for ACS than Swiss physicians. For both groups, the range between test and treatment thresholds was greater for ACS than for influenza (which is sensible, given the consequences of incorrect diagnosis). For pneumonia, US physicians had a trend towards higher test thresholds and lower treatment thresholds (48% vs 64%, p=0.076) than Swiss physicians. The DVT and UTI scenarios did not provide easily interpretable data, perhaps due to poor wording of the vignettes. We have developed a novel approach for determining decision thresholds. We found important differences in thresholds for US and Swiss physicians that may be a function of differences in healthcare systems. Our results can also guide development of clinical decision rules and guidelines.

Leptin and smoking cessation: secondary analyses of a randomized controlled trial assessing physical activity as an aid for smoking cessation.

BACKGROUND: Smokers have a lower body weight compared to non-smokers. Smoking cessation is associated with weight gain in most cases. A hormonal mechanism of action might be implicated in weight variations related to smoking, and leptin might be implicated. We made secondary analyses of an RCT, with a hypothesis-free exploratory approach to study the dynamic of leptin following smoking cessation. METHODS: We measured serum leptin levels among 271 sedentary smokers willing to quit who participated in a randomized controlled trial assessing a 9-week moderate-intensity physical activity intervention as an aid for smoking cessation. We adjusted leptin for body fat levels. We performed linear regressions to test for an association between leptin levels and the study group over time. RESULTS: One year after smoking cessation, the mean serum leptin change was +3.23 mg/l (SD 4.89) in the control group and +1.25 mg/l (SD 4.86) in the intervention group (p of the difference < 0.05). When adjusted for body fat levels, leptin was higher in the control group than in the intervention group (p of the difference < 0.01). The mean weight gain was +2.91 (SD 6.66) Kg in the intervention and +3.33 (SD 4.47) Kg in the control groups, respectively (p not significant). CONCLUSIONS: Serum leptin levels significantly increased after smoking cessation, in spite of substantial weight gain. The leptin dynamic might be different in chronic tobacco users who quit smoking, and physical activity might impact the dynamic of leptin in such a situation. Clinical trial registration number: NCT00521391.

Publication trends of shared decision making in 15 high impact medical journals: a full-text review with bibliometric analysis.

BACKGROUND: Shared Decision Making (SDM) is increasingly advocated as a model for medical decision making. However, there is still low use of SDM in clinical practice. High impact factor journals might represent an efficient way for its dissemination. We aimed to identify and characterize publication trends of SDM in 15 high impact medical journals. METHODS: We selected the 15 general and internal medicine journals with the highest impact factor publishing original articles, letters and editorials. We retrieved publications from 1996 to 2011 through the full-text search function on each journal website and abstracted bibliometric data. We included publications of any type containing the phrase "shared decision making" or five other variants in their abstract or full text. These were referred to as SDM publications. A polynomial Poisson regression model with logarithmic link function was used to assess the evolution across the period of the number of SDM publications according to publication characteristics. RESULTS: We identified 1285 SDM publications out of 229,179 publications in 15 journals from 1996 to 2011. The absolute number of SDM publications by journal ranged from 2 to 273 over 16 years. SDM publications increased both in absolute and relative numbers per year, from 46 (0.32% relative to all publications from the 15 journals) in 1996 to 165 (1.17%) in 2011. This growth was exponential (P < 0.01). We found fewer research publications (465, 36.2% of all SDM publications) than non-research publications, which included non-systematic reviews, letters, and editorials. The increase of research publications across time was linear. Full-text search retrieved ten times more SDM publications than a similar PubMed search (1285 vs. 119 respectively). CONCLUSION: This review in full-text showed that SDM publications increased exponentially in major medical journals from 1996 to 2011. This growth might reflect an increased dissemination of the SDM concept to the medical community.

Using a Semiautomated Procedure (CleanADHdata.R Script) to Clean Electronic Adherence Monitoring Data: Tutorial.

BACKGROUND: Patient 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. OBJECTIVE: We developed the computer script CleanADHdata.R to clean raw EM adherence data, and this tutorial is a guide for users. METHODS: In 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. RESULTS: We 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. CONCLUSIONS: The 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.

Single versus double retrograde intramedullary nail technique for treatment of displaced proximal humeral fractures in children: A retrospective cohort study.

Background: Highly displaced proximal humeral fractures in children with low remodeling potential need to be reduced and fixed. The use of two flexible retrograde nails became the most popular fixation technique due to the excellent functional outcome, the low complication rates, and the possibility of early mobilization. A modified single retrograde technique has been suggested by the authors to address the main disadvantage of this technique, the long operative duration. The aim of this study was to compare these techniques in terms of efficacy, and clinical and radiological outcomes. Methods: We performed a retrospective, monocentric study. Two groups of patients were defined: One was treated with the standard flexible retrograde double nail technique and the other with the modified single nail technique. The demographic and fracture characteristics were similar in both groups and the postoperative immobilization with a simple sling for 2 weeks. We compared the surgical duration for the initial fixation and hardware removal procedures. The Quick Disabilities of the Arm, Shoulder, and Hand score, the secondary displacement at 1-week follow-up, the radiological union at 6-week follow-up, and the perioperative and short-term complications were also assessed for both groups. Results: The surgical duration of the initial fixation procedure was significantly shorter in single nail technique group (p = 0.005). The percentage of excellent Quick Disabilities of the Arm, Shoulder, and Hand score (0) was similar in the two groups (p = 0.98). No secondary displacement was reported for the double nail technique group. In only one patient from the single nail technique group, we detected a secondary displacement at the first week control which did not need reoperation. In both groups, fractures were healed on the 6-week radiologic control. No cases of infection, superficial skin irritation, neurological damage, or complications related to implant removal were reported in both groups. Conclusions: The single nail technique of fixation proximal humeral fractures in children addresses the disadvantage of long surgical times, described until today, with the double nail technique without compromising the excellent functional and radiological short-term outcomes. Level of evidence: level III.