Fabio Valeri

FRUCTOSE AND TAGATOSE PROTECT AGAINST OXIDATIVE CELL INJURY BY IRON CHELATION

To further investigate the mechanism by which fructose affords protection against oxidative cell injury, cultured rat hepatocytes were exposed to cocaine (300 microM) or nitrofurantoin (400 microM). Both drugs elicited massively increased lactate dehydrogenase release. The addition of the ketohexoses D-fructose (metabolized via glycolysis) or D-tagatose (poor glycolytic substrate) significantly attenuated cocaine- and nitrofurantoin-induced cell injury, although both fructose and tagatose caused a rapid depletion of ATP and compromised the cellular energy charge. Furthermore, fructose, tagatose, and sorbose all inhibited in a concentration-dependent manner (0-16 mM) luminolenhanced chemiluminescence (CL) in cell homogenates, indicating that these compounds inhibit the iron-dependent reactive oxygen species (ROS)-mediated peroxidation of luminol. Indeed, both Fe2+ and Fe3+ further increased cocaine-stimulated CL, which was markedly quenched following addition of the ketohexoses. The iron-independent formation of superoxide anion radicals (acetylated cytochrome c reduction) induced by the prooxidant drugs remained unaffected by fructose or tagatose. The iron-chelator deferoxamine similarly protected against prooxidant-induced cell injury. In contrast, the nonchelating aldohexoses D-glucose and D-galactose did not inhibit luminol CL nor did they protect against oxidative cell injury. These data indicate that ketohexoses can effectively protect against prooxidant-induced cell injury, independent of their glycolytic metabolism, by suppressing the iron-catalyzed formation of ROS.

Strong Impact of Smoking on Multimorbidity and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Individuals in Comparison With the General Population

AIDS-associated morbidity has diminished due to excellent viral control. Multimorbidity are more prevalent and incident in Swiss HIV-positive persons compared to HIV-negative controls. However, smoking, but not HIV status, had a strong impact on cardiovascular risk and multimorbidity.

The impact of an individualized risk-adjusted approach on hypertension treatment in primary care.

Previous studies suggest that up to 60% of all patients with hypertension receive inappropriate treatment. Current 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines recommend taking cardiovascular risk factors into account when assessing treatment for patients with hypertension. The authors hypothesize that this approach will reduce the proportion of patients receiving inappropriate treatment. In this cross‐sectional study using electronic medical records of Swiss primary care patients, the authors estimate the proportion of patients receiving inappropriate treatment using two approaches: (1) based on a blood pressure threshold of 140/90 mm Hg; and (2) based on cardiovascular risk factors. A total of 22 434 patients with hypertension were identified. Based on these approaches, 72.7% and 44.6% of patients, respectively, qualified for drug treatment. In addition, 23.0% and 10.8% of patients, respectively, received inappropriate treatment. Application of the 2013 ESH/ESC guidelines reduced the proportion of patients receiving inappropriate treatment by 50%. This shows the major impact of risk adjustment and highlights the need for a patient‐centered approach in hypertension treatment.

Russians are the fastest 100-km ultra-marathoners in the world

Objectives A recent study investigating the top 10 100-km ultra-marathoners by nationality showed that Japanese runners were the fastest worldwide. This selection to top athletes may lead to a selection bias and the aim of this study was to investigate from where the fastest 100-km ultra-marathoners originate by considering all finishers in 100-km ultra-marathons since 1959. Methods We analysed data from 150,710 athletes who finished a 100-km ultra-marathon between 1959 and 2016. To get precise estimates and stable density plots we selected only those nationalities with 900 and more finishes resulting in 24 nationalities. Histograms and density plots were performed to study the distribution of race time. Crude mean, standard deviation, median, interquartile range (IQR), mode, skewness and excess of time for each nationality were computed. A linear regression analysis adjusted by sex, age and year was performed to study the race time between the nationalities. Histograms, density and scatter plots showed that some races seemed to have a time limit of 14 hours. From the complete dataset the finishes with more than 14 hours were removed (truncated dataset) and the same descriptive plots and analysis as for the complete dataset were performed again. In addition to the linear regression a truncated regression was performed with the truncated dataset to allow conclusion for the whole sample. To study a potential difference between races at home and races abroad, an interaction term race site home/abroad with nationality was included in the model. Results Most of the finishes were achieved by runners from Japan, Germany, Switzerland, France, Italy and USA with more than 260’000 (85%) finishes. Runners from Russia and Hungary were the fastest and runners from Hong Kong and China were the slowest finishers. Conclusion In contrast to existing findings investigating the top 10 by nationality, this analysis showed that ultra-marathoners from Russia, not Japan, were the fastest 100-km ultra-marathoners worldwide when considering all races held since 1959.

Referral determinants in Swiss primary care with a special focus on managed care

Studies have shown large variation of referral probabilities in different countries, and many influencing factors have been described. This variation is most likely explained by different healthcare systems, particularly to which extent primary care physicians (PCPs) act as gatekeepers. In Switzerland no mandatory gatekeeping system exists, however insurance companies offer voluntary managed care plans with reduced insurance premiums. We aimed at investigating the role of managed care plans as a potential referral determinant in a non-gatekeeping healthcare system. We conducted a cross-sectional study with 90 PCPs collecting data on consultations and referrals in 2012/2013. During each consultation up to six reasons for encounters (RFE) were documented. For each RFE PCPs indicated whether a referral was initiated. Determinants for referrals were analyzed by hierarchical logistic regression, taking the potential cluster effect of the PCP into account. To further investigate the independent association of the managed care plan with the referral probability, a hierarchical multivariate logistic regression model was applied, taking into account all available data potentially affecting the referring decision. PCPs collected data on 24’774 patients with 42’890 RFE, of which 2427 led to a referral. 37.5% of patients were insured in managed health care plans. Univariate analysis showed significant higher referral rates of patients with managed care plans (10.7% vs. 8.5%). The difference in referral probability remained significant after controlling for other confounders in the hierarchical multivariate regression model (OR 1.355). Patients in managed care plans were more likely to be referred than patients without such a model. These data contradict the argument that patients in managed care plans have limited healthcare access, but underline the central role of PCPs as coordinator of care.

Assessment of the safety climate in outpatient diagnostic services: Development and psychometric evaluation of a questionnaire

IntroductionSafe practice and safety culture are important issues in outpatient diagnostic imaging services. As questionnaires assessing safety culture through the measurement of safety climate in this setting are not yet available, the present study aimed to develop and validate such an instrument.Materials and methodsAfter adaptation of an existing questionnaire and qualitative pretesting, the instrument was tested by collaborators from three outpatient imaging services in Switzerland. Results were first assessed using descriptive statistics. Scores of individual services were compared using a Wilcoxon test assessing differences between rank distributions. The final instrument was tested for validity using inter-rater agreement measures, such as reliability within groups (rWG), and an intraclass correlation coefficient measure (ICC(1)). These measures allowed the assessment of validity of aggregation into a total score (rWG(j)) and validated the instrument for its capacity to distinguish various safety climates of different groups by comparing inter-rater agreement in the overall sample to inter-rater agreement of individual services (rWG) and by measuring group effects (ICC(1)). Furthermore, the final instrument was tested for internal consistency and reliability using Cronbach’s Alpha.ResultsSafety climate scores vary significantly between services. Inter-rater agreement measures show that item aggregation is justified and that the instrument distinguishes various patterns of safety climate. The final instrument proves to be valid, consistent and reliable.ConclusionsThe final instrument presents a valid, consistent and reliable option to measure safety climate in outpatient diagnostic imaging services. Results can be used as a basis for quality improvement.Key Points• An adapted questionnaire that assesses safety climate in outpatient diagnostic imaging services was developed and tested in Switzerland.• Psychometric evaluation showed the questionnaire to be a valid, consistent and reliable instrument.• Results are of interest for imaging services as well as for stakeholders interested more globally in monitoring and quality improvement.

Anticoagulation Control in Swiss Primary Care: Time in Therapeutic Range Percentages Exceed Benchmarks of Phase III Trials

Background: In randomized controlled trials, non-vitamin K antagonist oral anticoagulants (NOACs) demonstrated noninferiority to vitamin K antagonists (VKAs) in patients who spent limited time in therapeutic range (TTR). In real-life patients, TTR is known to vary significantly across countries and health-care settings. Objective: We aim to evaluate the quality of VKA treatment in Swiss primary care (PC) by comparing patients’ median TTR to levels achieved in the phase III NOAC trials RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48. Patient characteristics affecting TTR control shall be estimated. Methods: This is a retrospective longitudinal study in Swiss PC patients receiving VKA for ≥6 months. We identified patients from the PC research database FIRE (Family medicine International Classification of Primary Care Research using Electronic medical records) and calculated TTR according to Rosendaal formula. Comparative data from NOAC trials were retrieved from medical literature. Linear regression models were used to assess predictors of TTR. Results: Primary care encounters of 215 patients were analyzed. Like in the NOAC trials, median observation period was 2.2 years, but patients were older (67.9% vs 38% ≥75 years) and differed in terms of concomitant diseases and drugs. Median TTR was 75% (65% in the NOAC trials). Female sex was independently associated with a lower TTR and significantly modified by increasing age. Conclusion: Practitioners should consider that patients in NOAC trials are only partly representative of PC patients, particularly in terms of TTR control. Only a minority of the observed patients would require a therapy switch to NOACs due to inadequate TTR. Further research is needed in order to identify specific features of care management that are associated with these outcomes.