Hepatitis C virus seroprevalence in the general female population from 8 countries

Background: Hepatitis C virus (HCV) infection is a significant global health issue because it is widespread and persistent and can cause serious liver diseases. Objectives: The aim of this study is to estimate HCV prevalence in women from the general population in different geographical areas worldwide and to assess the potential role of sexual behaviour in the virus transmission. Study design: Each participating centre recruited a random sample of women from the general population aged from less than 20 to more than 75 years. The study included 8130 women from 8 countries with information on sociodemographic factors, reproductive and sexual behaviour, smoking habit and HPV DNA through individual interviews. A blood sample was also collected to perform serological tests. We estimated the prevalence ratios associated to HCV to evaluate the effect of sexual behaviour in viral transmission. Results: Women were reactive to a minimum of two HCV antigens, including at least one non structural protein were considered as positive (33% of the samples were classified as positive, 40% as negative, and 27% as indeterminate (N = 402), that were considered as not positive). The age-adjusted HCV seroprevalence varied significantly by regions (0.3% in Argentina to 21.1% in Nigeria). We found no association between HCV prevalence and age, educational level, smoking habit and any of the available variables for sexual behaviour and reproductive history. Conclusions: This large study showed heterogeneous distribution of HCV seroprevalence in female and provides evidence of the null impact of sexual behaviour in HCV transmission. (C) 2015 Elsevier B.V. All rights reserved

Clinical effectiveness of routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor

Pre-eclampsia affects 2%-8% of pregnancies and is one of the leading causes of maternal and perinatal morbidity and mortality. First-trimester screening using an algorithm that combines maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index and biomarkers (pregnancy-associated plasma protein-A and placental growth factor) is the method that achieves a greater diagnostic accuracy. It has been shown that daily salicylic acid administration before 16 weeks in women at a high risk for pre-eclampsia can reduce the incidence of preterm pre-eclampsia. However, no previous studies have evaluated the impact of routine first-trimester combined screening for pre-eclampsia with placental growth factor after being implemented in the clinical practice. This was a multicenter cohort study conducted in eight different maternities across Spain. Participants in the reference group were prospectively recruited between October 2015 and September 2017. Participants in the study group were retrospectively recruited between March 2019 and May 2021. Pre-eclampsia risk was calculated between 11 +0 and 13 +6 weeks using the Gaussian algorithm combining maternal characteristics, mean arterial pressure, uterine arteries pulsatility index, pregnancy-associated plasma protein-A and placental growth factor. Patients with a risk greater than 1/170 were prescribed daily salicylic acid 150 mg until 36 weeks. Patients in the reference group did not receive salicylic acid during gestation. A significant reduction was observed in preterm pre-eclampsia (OR 0.47; 95% CI: 0.30-0.73), early-onset (<34 weeks) pre-eclampsia (OR 0.35; 95% CI: 0.16-0.77), preterm small for gestational age newborn (OR 0.57; 95% CI: 0.40-0.82), spontaneous preterm birth (OR 0.72; 95% CI: 0.57-0.90), and admission to intensive care unit (OR 0.55; 95% CI: 0.37-0.81). A greater treatment adherence resulted in a significant reduction in adverse outcomes. Routine first-trimester screening for pre-eclampsia with placental growth factor leads to a reduction in preterm pre-eclampsia and other pregnancy complications. Aspirin treatment compliance has a great impact on the effectiveness of this screening program. Routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor resulted in a significant reduction of pre-eclampsia and other pregnancy complications

The use of the CNIC-Polypill in real-life clinical practice: opportunities and challenges in patients at very high risk of atherosclerotic cardiovascular disease – expert panel meeting report

Although the cardiovascular (CV) polypill concept is not new and several guidelines state that a CV polypill should be considered an integral part of a comprehensive CV disease (CVD) prevention strategy, there are still some barriers to its implementation in the real-world setting, mainly in secondary CV prevention. As the CNIC-polypill is the only one approved for secondary CV prevention in patients with atherosclerotic CVD in 27 countries worldwide, a panel of four discussants and 30 participants from 18 countries conveyed in a virtual meeting on April 21, 2022, to discuss key clinical questions regarding the practical use of the CNIC-Polypill and barriers to its implementation. Data presented showed that, although the use of the CV polypill is not explicitly mentioned in the current 2021 European Society of Cardiology guidelines on CVD prevention, it may be used in any patient for secondary CVD prevention tolerating all their components to improve outcomes through different aspects. The favourable results of the Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) trial now reinforce this recommendation. The panellists presented algorithms on how to switch from any baseline regimen when starting treatment with the CNIC-polypill in different situations, including patients with hypertension, dyslipidaemia, and a previous CV event; at discharge after a cardiovascular event; in chronic ischemic conditions; and in cases of polypharmacy. The panellists and expert discussants did agree that available studies conducted so far with the CNIC-polypill demonstrate that it is as efficacious as the monocomponents, equipotent drugs, or other therapies; reduces the risk of experiencing recurrent major CV events; improves medication adherence; reduces health care costs and resources compared to patients treated with loose drugs; and the patients prefer it over the multipill strategy. In conclusion, the data presented by the participants provided the evidence behind the use of the CNIC-polypill to help fulfil the goal of encouraging its adoption by physicians.info:eu-repo/semantics/publishedVersio

Infection of the malaria mosquito, Anopheles gambiae, with two species of entomopathogenic fungi: effects of concentration, co-formulation, exposure time and persistence

<p>Abstract</p> <p>Background</p> <p>Entomopathogenic fungi <it>Metarhizium anisopliae </it>and <it>Beauveria bassiana </it>isolates have been shown to infect and reduce the survival of mosquito vectors.</p> <p>Methods</p> <p>Here four different bioassays were conducted to study the effect of conidia concentration, co-formulation, exposure time and persistence of the isolates <it>M. anisopliae </it>ICIPE-30 and <it>B. bassiana </it>I93-925 on infection and survival rates of female <it>Anopheles gambiae sensu stricto</it>. Test concentrations and exposure times ranged between 1 × 10⁷- 4 × 10¹⁰conidia m^-2and 15 min - 6 h. In co-formulations, 2 × 10¹⁰conidia m^-2of both fungus isolates were mixed at ratios of 4:1, 2:1, 1:1,1:0, 0:1, 1:2 and 1:4. To determine persistence, mosquitoes were exposed to surfaces treated 1, 14 or 28 d previously, with conidia concentrations of 2 × 10⁹, 2 × 10¹⁰or 4 × 10¹⁰.</p> <p>Results</p> <p>Mosquito survival varied with conidia concentration; 2 × 10¹⁰conidia m^-2was the concentration above which no further reductions in survival were detectable for both isolates of fungus. The survival of mosquitoes exposed to single and co-formulated treatments was similar and no synergistic or additive effects were observed. Mosquitoes were infected within 30 min and longer exposure times did not result in a more rapid killing effect. Fifteen min exposure still achieved considerable mortality rates (100% mortality by 14 d) of mosquitoes, but at lower speed than with 30 min exposure (100% mortality by 9 d). Conidia remained infective up to 28 d post-application but higher concentrations did not increase persistence.</p> <p>Conclusion</p> <p>Both fungus isolates are effective and persistent at low concentrations and short exposure times.</p

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years