Does the advertisement in Swiss pharmacy windows rest on evidence-based medicine? An observational study.

OBJECTIVES: The aim of the study was to analyse the proportion of evidence-based medication displayed in pharmacies and compare it between the different linguistic regions of the country, at different times of the year to determine the amount of proven effective medications indirectly recommended to the public in different parts of Switzerland. DESIGN: This is an observational study conducted by medical doctors in the department of internal medicine at the Spitalzentrum Biel, Switzerland. SETTING: The observation took place from July 2019 to May 2020. From a total of 1800 pharmacies in Switzerland, 68 different pharmacies were selected across the 3 main linguistic regions and the medication on display in their windows were examined 4 times a year regarding their efficacy. The displays of medication with or without evidence-based efficacy were described using absolute numbers and proportions and compared between the different linguistic regions at different seasons using χ2. PARTICIPANTS: There were no human or animal participants involved in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is the proportion of medication displayed in pharmacy windows with a proven effectiveness in medical literature. The secondary outcome was the variability of the primary outcome over time (seasonal changes), over the different linguistic regions of Switzerland and between chains and privately owned pharmacies. RESULTS: We examined 970 medications and found that over the whole year, there is a high proportion of non-evidence-based drugs (56,9%) displayed in pharmacies. Swiss German cantons display significantly more non-evidence-based medications in winter. We found no statistical difference for other seasons or between chains and privately owned pharmacies. CONCLUSION: Pharmacies in Switzerland tend to display significantly more non-evidence-based drugs, thus indirectly recommending them to the public. In a time of necessary expansion of self-medication by the population, this could incite consumers to buy drugs without proven effectiveness.

Differences in duration of anticoagulation after pulmonary embolism and deep vein thrombosis: Findings from the SWIss Venous ThromboEmbolism Registry (SWIVTER).

BACKGROUND: Although the two manifestations of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE), vary considerably, the consensus guidelines recommend similar algorithms for therapeutic anticoagulation in both conditions. Real-world data assessing contemporary management strategies in PE and DVT alone may help tailoring future recommendations towards more individualized patient care. METHODS: In the present analysis, we compared demographics, comorbidities, treatment patterns, and clinical outcomes of PE versus DVT only among 2062 consecutive patients with confirmed VTE enrolled by 11 acute care hospitals between November 2012 and February 2015 in the SWIss Venous ThromboEmbolism Registry (SWIVTER). RESULTS: Overall, 1246 (60 %) patients were diagnosed with PE. In comparison to DVT alone, PE patients were older (66 vs. 59 years; p < 0.001), more frequently had acute and chronic comorbidities, less frequently had prior VTE and hormone replacement, and were less often pregnant. VTE was considered similarly often provoked in patients with PE and DVT alone (33.8 % vs. 33.5 %; p = 0.88). Anticoagulation for an indefinite duration was more often prescribed to patients with PE than those with DVT alone (45.7 vs. 19.6 %; p < 0.001), and PE diagnosis was the strongest independent predictor of indefinite anticoagulation (OR 3.21; 95 % CI 2.55-4.06; p < 0.001). Diagnosis of PE was associated with both increased risk of 90-day mortality (HR 2.31, 95 % CI 1.44-3.71; p = 0.001) and major bleeding (HR 3.88, 95 % CI 1.63-9.22; p = 0.002). CONCLUSIONS: Our analysis affirms differences in demographics, risk factors, and clinical outcomes of PE versus DVT alone. In routine clinical practice, duration of anticoagulation is being managed differently between the two manifestations of VTE, in contrast to recommendations of the current consensus guidelines.

[Relevance of interventions and support for relatives of an individual who made a suicide attempt]. / Importance de l'accompagnement des proches confrontés à une tentative de suicide.

Suicide and suicide attempt has an impact not only on the suicidal individual but also on his relatives. People expose to suicidal behavior of a close relation are confronted to death or to death threat and are subject to various signs such as anxiety, depression, specially linked to trauma. Therefore, it is essential to support those relatives in their suffering. Three types of intervention are distinguished according to timing: immediate, post-immediate and mid-to-long term interventions.

Le suicide avéré et la tentative de suicide ont un impact important sur la personne suicidaire mais aussi sur ses proches. Ces derniers se voient confrontés à la mort ou à une menace de mort, ce qui peut entraîner la survenue d'une panoplie de syndromes dépressifs et anxieux, surtout liés au traumatisme. Il est essentiel d'intervenir auprès des proches pour accompagner la souffrance psychique souvent présentée. Les interventions proposées sont subdivisées en trois temps distincts : interventions immédiates, postimmédiates et à moyen, voire à long terme.

Pulmonary embolism and deep vein thrombosis: Similar but different.

INTRODUCTION: Pulmonary embolism (PE) and deep vein thrombosis (DVT), the two clinical manifestations of venous thromboembolism (VTE), constitute a major global burden of cardiovascular disease. They are often referred to as one disease but several patient characteristics, risk factors, real-world treatment, and clinical outcomes may differ substantially between PE and DVT alone. MATERIALS AND METHODS: We conducted a narrative review of the state-of-the-art literature on the topic of PE and DVT alone using PubMed, Google scholar, and MEDLINE databases and the most established international consensus statement guidelines for the management of VTE, focusing on the recommendations for diagnosis and treatment but also including epidemiological and clinical characteristics of VTE, highlighting similarities and differences between PE and DVT alone. RESULTS: Several patient characteristics, risk factors, clinical manifestations, and outcomes differ substantially between PE versus DVT alone. Nevertheless, recommendations for both diagnosis and treatment are strikingly similar in the current guidelines for the management of DVT and PE, except for the indication for advanced reperfusion therapies. CONCLUSIONS: The differences in risk factors, clinical manifestations, and clinical outcomes between patients with PE versus DVT alone are only marginally addressed in the current consensus guidelines. More data is needed allowing proposal of evidence-based adjustments in the diagnostic and therapeutic strategies for these two manifestations of VTE. Tailored risk stratification and individualized management strategies for patients with PE and DVT alone may lead to a better prognosis, less recurrence and complications, and possibly to a gain of quality-adjusted life years in patients with VTE.

Synthesis and Pharmacological Characterization of 2-Aminoethyl Diphenylborinate (2-APB) Derivatives for Inhibition of Store-Operated Calcium Entry (SOCE) in MDA-MB-231 Breast Cancer Cells.

Calcium ions regulate a wide array of physiological functions including cell differentiation, proliferation, muscle contraction, neurotransmission, and fertilization. The endoplasmic reticulum (ER) is the major intracellular Ca2+ store and cellular events that induce ER store depletion (e.g., activation of inositol 1,4,5-triphosphate (IP3) receptors) trigger a refilling process known as store-operated calcium entry (SOCE). It requires the intricate interaction between the Ca2+ sensing stromal interaction molecules (STIM) located in the ER membrane and the channel forming Orai proteins in the plasma membrane (PM). The resulting active STIM/Orai complexes form highly selective Ca2+ channels that facilitate a measurable Ca2+ influx into the cytosol followed by successive refilling of the ER by the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). STIM and Orai have attracted significant therapeutic interest, as enhanced SOCE has been associated with several cancers, and mutations in STIM and Orai have been linked to immunodeficiency, autoimmune, and muscular diseases. 2-Aminoethyl diphenylborinate (2-APB) is a known modulator and depending on its concentration can inhibit or enhance SOCE. We have synthesized several novel derivatives of 2-APB, introducing halogen and other small substituents systematically on each position of one of the phenyl rings. Using a fluorometric imaging plate reader (FLIPR) Tetra-based calcium imaging assay we have studied how these structural changes of 2-APB affect the SOCE modulation activity at different compound concentrations in MDA-MB-231 breast cancer cells. We have discovered 2-APB derivatives that block SOCE at low concentrations, at which 2-APB usually enhances SOCE.

Development of a cyclosporin A derivative with excellent anti-hepatitis C virus potency.

Synthetic modification of cyclosporin A at P3-P4 positions led to the discovery of NIM258, a next generation cyclophilin inhibitor with excellent anti-hepatitis C virus potency, with decreased transporter inhibition, and pharmacokinetics suitable for coadministration with other drugs. Herein is disclosed the evolution of the synthetic strategy to from the original medicinal chemistry route, designed for late diversification, to a convergent and robust development synthesis. The chiral centers in the P4 fragment were constructed by an asymmetric chelated Claisen rearrangement in the presence of quinidine as the chiral ligand. Identification of advanced crystalline intermediates enabled practical supply of key intermediates. Finally, macrocyclization was carried out at 10% weight concentration by a general and unconventional "slow release" concept.