Sequence analysis of the 5' untranslated region in isolates of at least four genotypes of hepatitis C virus in The Netherlands

The RNAs of hepatitis C virus (HCV) isolates from 62 patients with chronic HCV infection were analyzed by direct sequencing of the 5' untranslated region. Two important sequence motifs were recognized: one between positions -170 and -155 and the other between positions -132 and -117. These motifs are partly complementary. All three previously published genotypes were observed; 34 (55%) isolates were classified as type 1 (including prototype [from the United States] and HCV-BK [from Japan] sequences), 11 (18%) were classified as type 2 (including HC-J6 and HC-J8), and 12 (19%) were classified as type 3 (including EB1); one patient was infected with genotypes 1 and 2. Four (6%) isolates showed aberrant sequences and were therefore provisionally classified as genotype 4. These results indicate the significance of sequence variation among the 5' untranslated regions of different HCV genotypes and indicate that this region could possibly be used for consistent genotyping of HCV isolates

L’influence des relations familiales et sociales sur la consommation de médicaments psychotropes chez les personnes âgées

Les psychotropes occupent le deuxième rang dans la consommation de médicaments chez les personnes âgées. L'objectif de cette étude est de vérifier un modèle explicatif de la consommation de psychotropes dans cette population. Notre principale hypothèse est que la qualité des relations qu'entretient une personne âgée avec autrui, et particulièrement avec ses enfants, a une influence directe sur son bien-être psychologique, lequel a une influence directe sur la non-consommation de psychotropes. Une enquête a été réalisée auprès d'un échantillon de 500 personnes âgées de 65 à 84 ans, vivant à domicile. Au cours des trois mois précédant l'entrevue, 31,8 % des répondants ont consommé des psychotropes. Les données empiriques n'ayant pas permis de vérifier le modèle théorique retenu, des analyses multivariées ont conduit à l'élaboration d'un modèle explicatif de la consommation qui met en évidence que le bien-être psychologique et la santé sont les meilleurs prédicteurs de cette consommation. Un bien-être psychologique élevé diminue la consommation alors qu'un mauvais état de santé l'augmente. Les relations sociales influencent directement le bien-être psychologique alors que les relations familiales ont un effet de moindre importance. Le modèle explicatif proposé explique 13 % du phénomène de la consommation de psychotropes chez les personnes âgées.Psychotropic drugs are the second most commonly used medication by Quebec's elderly. The objective of this study is to test a theoretical model of psychotropic drug use in the elderly. The principal hypothesis is that the quality of relationships the elderly person has with others, particularly with his or her children, has a direct influence on his or her psychological well-being, which, in turn, directly affects the consumption of psychotropic agents. A survey was conducted on a sample of 500 elderly people, aged 65-84 years, living at home. 31.8% of the respondents used psychotropic drugs during the three-month period preceding the interview. Path analysis led to the elaboration of a modified model for the consumption of psychotropic drugs by the elderly which indicates that the best predictors of consumption are both the psychological well-being and the state of health of the individual. More elevated is the psychological well-being, less is the consumption of psychotropic drugs, whereas poor health condition increases it. The quality of an individual's social relationships has a direct influence on his or her psychological well-being, whereas family relationships are of lesser importance. Our model accounts for 13% of the predictors of psychotropic consumption by the elderly

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Large-scale Survey of the Impact of Complementary Medicine on Side-effects of Adjuvant Hormone Therapy in Patients with Breast Cancer

Background/Aim: The present clinical investigation was performed to confirm the benefit of complementary medicine in patients with breast cancer undergoing adjuvant hormone therapy (HT). Patients and Methods: The patients (n=1561) were treated according to international guidelines. All patients suffered from arthralgia and mucosal dryness induced by the adjuvant HT. In order to reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes (bromelaine and papain) and Lens culinaris lectin. On case report formulas, self assessment arthralgia and mucosal dryness were documented before and four weeks after complementary treatment. Validation was carried-out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely poor tolerability). A total of 1,165 patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. Results: Overall, 62.6% of patients (729 out of 1,165) suffering from severe arthralgia and 71.7% of patients (520 out of 725) with severe mucosal dryness significantly benefited from complementary medicine. Mean scores of symptoms declined from 4.83 before treatment to 3.23 after four weeks of treatment for arthralgia and from 4.72 before treatment to 2.99 after four weeks of treatment for mucosal dryness, the primary aims of the present investigation. The reduction of side-effects of HT was statistically significant (p<0.001) after four weeks. Conclusion: This investigation confirms studies suggesting a benefit of complementary treatment with the combination of sodium selenite, proteolytic enzymes and L. culinaris lectin in patients with breast cancer

Complementary Medicine Down-regulates Side-effects of Hormone Therapy in Prostate Cancer Patients

Aim: The present clinical investigation was performed to evaluate the benefits of complementary medicine in prostate cancer patients undergoing hormone therapy (HT). Patients and Methods: Patients (N=93) were treated according to international guidelines. All patients suffered from side-effects induced by the HT. To reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes and Lens culinaris (Lc) lectin. On case report formulas (CRFs), self assessment of defined side-effects of HT (arthralgia, mucosal dryness, bone pain and hot flushes) were documented before (T-0) and on days 25 (T-1) and 50 (T-2) after complementary treatment. Validation was carriedout by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely bad tolerability), however, only patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. Results: The severity of side-effects of HT was reduced by complementary treatment with sodium selenite, proteolytic plant enzymes and Lc-lectin. The mean scores of side-effects declined for arthralgia from 4.72 (T-0) to 3.66 (T-1) to 2.76 (T-2), for mucosal dryness from 4.45 (T-0) to 3.65 (T-1) to 2.90 (T-2), for bone pain from 4.74 (T-0) to 3.44 (T-1) to 2.82 (T-2), for hot flushes from 4.97 (T-0) to 3.70 (T-1) to 3.15 (T-2). The reduced severity of the side-effects was statistically significant (p<0.001) for T-1 and T-2, compared to T-0. Conclusion: This investigation demonstrates benefits of indication-based complementary treatment with the combination of sodium selenite, proteolytic plant enzymes and Lc-lectin in prostate cancer patients, e.g. reduction of side-effects of HT

Single-Bundle Versus Double-Bundle Reconstruction for Anterior Cruciate Ligament Rupture: A Meta-Analysis-Does Anatomy Matter?

Purpose: To determine whether double-bundle anterior cruciate ligament reconstruction leads to better restoration of anterior and rotational laxity and range of motion than single-bundle reconstruction. Methods: A search was performed in the Medline, Embase, CINAHL, and Cochrane databases. All randomized, quasi-randomized, and observational clinical trials that reported the outcome of double-versus single-bundle anterior cruciate ligament reconstruction were included in our meta-analysis. The primary outcomes were anterior laxity (KT arthrometer; MEDmetric, San Diego, CA), pivot shift, and range of motion. Subgroup analyses were performed for more than 2 years' follow-up, anatomic reconstruction, and nonanatomic reconstruction. The quality of the included studies was scored by use of the GRADE Checklist. Results: Included 12 studies in this meta-analysis, 5 of which were randomized. There was a statistically significant difference in favor of double-bundle reconstruction for anterior laxity (KT arthrometer difference, -0.6 mm), Lachman test (64% risk reduction of positive Lachman), and pivot-shift test (69% risk reduction of positive shift). Similar results were found for the subgroup with more than 2 years' follow-up and anatomic reconstructions. There were no significant differences for the subgroup with nonanatomic reconstructions, except a 2.6 times risk increase of extension deficit with nonanatomic double-bundle reconstruction compared with nonanatomic single-bundle reconstruction. Most of the included studies were found to have at least one serious limitation in study design. Conclusions: In comparison with single-bundle reconstruction, double-bundle reconstruction showed less anterior laxity, as measured by the KT arthrometer and Lachman test, and better rotational laxity, as measured by the pivot-shift test. The majority of the included studies had at least one major limitation in study design that decreased the quality of the study. Level of Evidence: Level I, meta-analysi

Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: The GAUSS-3 randomized clinical trial

Importance: Muscle-related statin intolerance is reported by 5%to 20%of patients. Objective: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. Design, Setting, and Participants: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. Interventions: Phase A: atorvastatin (20mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420mg monthly) or oral ezetimibe (10mg daily). Main Outcome and Measures: Coprimary end pointswere the mean percent change in LDL-C level from baseline to the mean ofweeks 22 and 24 levels and from baseline toweek 24 levels. Results: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9]mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72]mg/dL). For the mean ofweeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7%(95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5%(95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptomswere reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drugwas stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). Conclusions and Relevance: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety