Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction

Background The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. Methods We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. Results There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. Conclusions Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.

Angiotensin-Neprilysin inhibition in heart failure with preserved ejection fraction

Background: the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. Methods: we randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. Results: there were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. Conclusions: sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.)

Dengue Fever in Italy: The “Eternal Return” of an Emerging Arboviral Disease

Enhanced surveillance for dengue virus (DENV) infections in Italy has been implemented since 2012, with annual reports from the National Health Institute. In this study, we summarize available evidence on the epidemiology of officially notified DENV infections from 2010–2021. In total, 1043 DENV infection cases were diagnosed, and most of them occurred in travelers, with only 11 autochthonous cases. The annual incidence rates of DENV infections peaked during 2019 with 0.277 cases per 100,000 (95% confidence interval [95% CI] 0.187–0.267), (age-adjusted incidence rate: 0.328, 95% CI 0.314–0.314). Cases of DENV were clustered during the summer months of July (11.4%), August (19.3%), and September (12.7%). The areas characterized by higher notification rates were north-western (29.0%), and mostly north-eastern Italy (41.3%). The risk for DENV infection in travelers increased in the time period 2015–2019 (risk ratio [RR] 1.808, 95% CI 1.594–2.051) and even during 2020–2021 (RR 1.771, 95% CI 1.238–2.543). Higher risk for DENV was additionally reported in male subjects compared with females subjects, and aged 25 to 44 years, and in individuals from northern and central Italy compared to southern regions and islands. In a multivariable Poisson regression model, the increased number of travelers per 100 inhabitants (incidence rate ratio [IRR] 1.065, 95% CI 1.036–1.096), the incidence in other countries (IRR 1.323, 95% CI 1.165–1.481), the share of individuals aged 25 to 44 years (IRR 1.622, 95% CI 1.338–1.968), and foreign-born residents (IRR 2.717, 95% CI 1.555–3.881), were identified as effectors of annual incidence. In summary, although the circulation of DENV remains clustered among travelers, enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures

Epidemiology and risk factors for Carbapenemase-Producing Enterobacteriaceae carriage in the hospital: a population-based nested case-control study

Objective: This study aims to study the epidemiology of Carbapenemase-producing Enterobacteriaceae (CPE) in Hong Kong. / Methods: This is a longitudinal population-based study reporting monthly CPE incidence rate and a nested case-control study for identifying risk factors for CPE carriage. The cases were patients with at least one CPE positive genotypic test, while the controls were randomly selected from the cohort with negative tests. Up to four controls per case were matched by sex, age group, and admission year-month. The independent risk factors were identified from a conditional logistic regression with potential covariates. / Results: From 1st January 2008 to 31st December 2019, 8,588 patients received CPE genotyping tests, and 2,353 had at least one positive result. Class B carbapenemase was the predominant enzyme in the samples (78.6%). The incidence rate increased from 0.04 in 2015 to 1.62 in 2019 per 10,000 person-year. In the nested case-control study, 1709 cases and 6664 controls were matched. Previous use of any beta-lactam antibiotics [Odds ratio:1.37 (1.22-1.53), p<.001] was found as an independent risk factor for carriage of CPE. / Conclusion: The carriage of CPE was found with an increasing trend in Hong Kong. Previous use of any beta-lactam antibiotics is a risk factor for CPE. / Summary: The incidence rate of Carbapenemase-producing Enterobacteriaceae is increasing in Hong Kong, with the predominant enzyme of class B carbapenemase. With multivariable conditional logistic regression, the previous use of any beta-lactam antibiotics was found as an independent risk factor for CPE carriage

Stroke, mortality, and competing risks: analyses in a large cohort of patients with atrial fibrillation

Patients with atrial fibrillation (AF) are at increased risk of stroke. Warfarin anticoagulation therapy reduces the incidence of stroke and increases the incidence of hemorrhagic events. This dissertation further informs the decision to use anticoagulation therapy in AF patients by examining outcomes in patients with major hemorrhages, further examination of stroke risk in diabetic patients with AF, and by evaluating the association between warfarin and stroke while accounting for competing risk events. These studies utilized data from the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) and ATRIA-CVRN (Cardiovascular Research Network) (Study 1 only) studies which consist of patients from Kaiser Permanente Northern and Southern California. Study 1 examined short and long-term mortality in patients who experienced major gastrointestinal (GI) hemorrhages. In the ATRIA cohort, patients using and not using warfarin at the time of GI hemorrhage were equally likely to die within 30-days, while in ATRIA-CVRN, patients using warfarin were much less likely to die within 30-days (adjusted mortality rate ratio (aMRR): 0.33, 95% CI: 0.16-0.70). For longer-term mortality, both cohorts were consistent with a reduced mortality rate among patients whose GI hemorrhage occurred while using warfarin. Study 2 assessed the association between diabetes characteristics (duration of diabetes and glycemic control) and incidence of ischemic stroke among patients with AF and diabetes. Duration ≥ 3 years was associated with a large increase in rate of stroke (adjusted hazard ratio (aHR): 2.04, 95% CI: 1.27-3.26) compared to patients with duration < 3 years. Patients with the poorest glycemic control (hemoglobin A1c (HbA1c) values ≥ 9.0%) did not have an increased rate of ischemic stroke compared to patients with HbA1c < 7.0%. Study 3 evaluated the association between warfarin and thromboembolism in analyses that did and did not account for competing death events. In analyses not accounting for competing events, the adjusted HR was 0.61 (95% CI: 0.54-0.69), and after accounting for competing death events this association was attenuated (aHR: 0.87, 95% CI: 0.77-0.99). In summary, these studies add to the literature about the benefits of warfarin therapy and risk of stroke in patients with AF, findings that can improve decisions about use of anticoagulants in patients with AF

Robotic versus laparoscopic approach in colonic resections for cancer and Benign diseases. Systematic review and meta-analysis

Objectives The aim of this systematic review and meta-Analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. Materials and Methods A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. Results A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD-0.51, P = 0.003) and the length of hospital stay (MD-0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD-16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD-0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. Conclusions The present meta-Analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections. Copyright: © 2015 Trastulli et al.OBJECTIVES: The aim of this systematic review and meta-analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. MATERIALS AND METHODS: A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. RESULTS: A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD -0.51, P = 0.003) and the length of hospital stay (MD -0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD -16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD -0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. CONCLUSIONS: The present meta-analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections

Income Distributions, Inequality, and Poverty in Asia, 1992–2010

Income distributions for developing countries in Asia are modeled using beta-2 distributions, which are estimated by a method of moments procedure applied to grouped data. Estimated parameters of these distributions are used to calculate measures of inequality, poverty, and pro-poor growth in four time periods over 1992–2010. Changes in these measures are examined for 11 countries, with a major focus on the People’s Republic of China (PRC), India, and Indonesia, which are separated into rural and urban regions. We find that the PRC has grown rapidly with increasing inequality accompanying this growth. India has been relatively stagnant. Indonesia has grown rapidly after suffering an initial set back from the Asian financial crisis in 1997

Hand washing promotion for preventing diarrhoea.

BACKGROUND: Diarrhoea accounts for 1.8 million deaths in children in low- and middle-income countries (LMICs). One of the identified strategies to prevent diarrhoea is hand washing. OBJECTIVES: To assess the effects of hand washing promotion interventions on diarrhoeal episodes in children and adults. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (27 May 2015); CENTRAL (published in the Cochrane Library 2015, Issue 5); MEDLINE (1966 to 27 May 2015); EMBASE (1974 to 27 May 2015); LILACS (1982 to 27 May 2015); PsycINFO (1967 to 27 May 2015); Science Citation Index and Social Science Citation Index (1981 to 27 May 2015); ERIC (1966 to 27 May 2015); SPECTR (2000 to 27 May 2015); Bibliomap (1990 to 27 May 2015); RoRe, The Grey Literature (2002 to 27 May 2015); World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), metaRegister of Controlled Trials (mRCT), and reference lists of articles up to 27 May 2015. We also contacted researchers and organizations in the field. SELECTION CRITERIA: Individually randomized controlled trials (RCTs) and cluster-RCTs that compared the effects of hand washing interventions on diarrhoea episodes in children and adults with no intervention. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CIs). We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: We included 22 RCTs: 12 trials from child day-care centres or schools in mainly high-income countries (54,006 participants), nine community-based trials in LMICs (15,303 participants), and one hospital-based trial among people with acquired immune deficiency syndrome (AIDS) (148 participants).Hand washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevents around one-third of diarrhoea episodes in high income countries (rate ratio 0.70; 95% CI 0.58 to 0.85; nine trials, 4664 participants, high quality evidence), and may prevent a similar proportion in LMICs but only two trials from urban Egypt and Kenya have evaluated this (rate ratio 0.66, 95% CI 0.43 to 0.99; two trials, 45,380 participants, low quality evidence). Only three trials reported measures of behaviour change and the methods of data collection were susceptible to bias. In one trial from the USA hand washing behaviour was reported to improve; and in the trial from Kenya that provided free soap, hand washing did not increase, but soap use did (data not pooled; three trials, 1845 participants, low quality evidence).Hand washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (rate ratio 0.72, 95% CI 0.62 to 0.83; eight trials, 14,726 participants, moderate quality evidence). However, six of these eight trials were from Asian settings, with only single trials from South America and sub-Saharan Africa. In six trials, soap was provided free alongside hand washing education, and the overall average effect size was larger than in the two trials which did not provide soap (soap provided: rate ratio 0.66, 95% CI 0.56 to 0.78; six trials, 11,422 participants; education only: rate ratio: 0.84, 95% CI 0.67 to 1.05; two trials, 3304 participants). There was increased hand washing at major prompts (before eating/cooking, after visiting the toilet or cleaning the baby's bottom), and increased compliance to hand hygiene procedure (behavioural outcome) in the intervention groups than the control in community trials (data not pooled: three trials, 3490 participants, high quality evidence).Hand washing promotion for the one trial conducted in a hospital among high-risk population showed significant reduction in mean episodes of diarrhoea (1.68 fewer) in the intervention group (Mean difference 1.68, 95% CI 1.93 to 1.43; one trial, 148 participants, moderate quality evidence). There was increase in hand washing frequency, seven times per day in the intervention group versus three times in the control in this hospital trial (one trial, 148 participants, moderate quality evidence).We found no trials evaluating or reporting the effects of hand washing promotions on diarrhoea-related deaths, all-cause-under five mortality, or costs. AUTHORS' CONCLUSIONS: Hand washing promotion probably reduces diarrhoea episodes in both child day-care centres in high-income countries and among communities living in LMICs by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term

Investigation of Anaplasma marginale Seroprevalence in a Traditionally Managed Large California Beef Herd.

Recent observations by stakeholders suggested that ecosystem changes may be driving an increased incidence of bovine erythrocytic anaplasmosis, resulting in a reemerging cattle disease in California. The objective of this prospective cohort study was to estimate the incidence of Anaplasma marginale infection using seroconversion in a northern California beef cattle herd. A total of 143 Black Angus cattle (106 prebreeding heifers and 37 cows) were enrolled in the study. Serum samples were collected to determine Anaplasma marginale seroprevalence using a commercially available competitive enzyme-linked immunosorbent assay test kit. Repeat sampling was performed in seronegative animals to determine the incidence density rate from March through September (2013). Seroprevalence of heifers was significantly lower than that of cows at the beginning of the study (P &lt; 0.001) but not at study completion (P = 0.075). Incidence density rate of Anaplasma marginale infection was 8.17 (95% confidence interval: 6.04, 10.81) cases per 1000 cow-days during the study period. Study cattle became Anaplasma marginale seropositive and likely carriers protected from severe clinical disease that might have occurred had they been first infected as mature adults. No evidence was found within this herd to suggest increased risk for clinical bovine erythrocytic anaplasmosis