Coronary computed tomography angiography compared with single photon emission computed tomography myocardial perfusion imaging as a guide to optimal medical therapy in patients presenting with stable angina: The RESCUE trial

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of 1.3 (95% CI=0, 1.605). One thousand fifty participants from 44 sites were randomized to CCTA (n=518) or SPECT (n=532). Mean follow-up time was 16.2 (SD 7.9) months. There were no cardiac-related deaths. In patients with a negative CCTA there was 1 acute myocardial infarction; in patients with a negative SPECT examination there were 2 acute myocardial infarctions; and for positive CCTA and SPECT, 1 acute myocardial infarction each. Participants in the CCTA arm had a similar rate of MACE or revascularization compared with those in the SPECT myocardial perfusion imaging arm, (HR, 1.03; 95% CI=0.61-1.75)

Association between respiratory syncytial virus-associated acute lower respiratory infection in early life and recurrent wheeze and asthma in later childhood

Background. Recurrent wheeze and asthma in childhood are commons causes of chronic respiratory morbidity globally. We aimed to explore the association between respiratory syncytial virus (RSV) infection in early life and subsequent respiratory sequelae up to age 12 years. Methods. We estimated the strength of association by 3 control groups and 3 follow-up age groups, with data from studies published between January 1995 and May 2018. We also estimated associations by diagnostic criteria, age at infection, and high-risk population. Results. Overall, we included 41 studies. A statistically significant association was observed between early life RSV infection and subsequent childhood recurrent wheeze, in comparison to those who were healthy or those without respiratory symptoms: OR 3.05 (95% confidence interval [CI], 2.50-3.71) for 0 to <36 months follow-up age; OR 2.60 (95% CI, 1.67-4.04) for 36-72 months; and OR 2.14 (95% CI, 1.33-3.45) for 73-144 months. For the subsequent development of asthma, a statistically significant association was observed only in relation to those aged 73-144 months at follow-up: OR 2.95 (95% CI, 1.96-4.46). Conclusions. Further studies using standardized definitions and from diverse settings are needed to elucidate the role of confounders and provide more robust estimates

The etiological role of common respiratory viruses in acute respiratory infections in older adults: A systematic review and meta-analysis

Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9-18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4-15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3-41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7-13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0-4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report

Effect of Continuous Glucose Monitoring on Glycemic Control, Acute Admissions, and Quality of Life: A Real-World Study

Context: Randomized controlled trials evaluating real-time continuous glucose monitoring (RT-CGM) patients with type 1 diabetes (T1D) show improved glycemic control, but limited data are available on real-world use. Objective: To assess impact of RT-CGM in real-world settings on glycemic control, hospital admissions, work absenteeism, and quality of life (QOL). Design: Prospective, observational, multicenter, cohort study. Participants: A total of 515 adults with T1D on continuous subcutaneous insulin infusion (CSII) therapy starting in the Belgian RT-CGM reimbursement program. Intervention: Initiation of RT-CGM reimbursement. Main Outcome Measure: Hemoglobin A1c (HbA(1c)) evolution from baseline to 12 months. Results: Between September 1, 2014, and December 31, 2016, 515 adults entered the reimbursement system. Over this period, 417 (81%) patients used RT-CGM for at least 12 months. Baseline HbA(1c) was 7.7 +/- 0.9% (61 +/- 9.8 mmol/mol) and decreased to 7.4 +/- 0.8% (57 +/- 8.7 mmol/mol) at 12 months (P < 0.0001). Subjects who started RT-CGM because of insufficient glycemic control showed stronger decrease in HbA(1c) at 4, 8, and 12 months compared with patients who started because of hypoglycemia or pregnancy. In the year preceding reimbursement, 16% of patients were hospitalized for severe hypoglycemia or ketoacidosis in contrast to 4% (P < 0.0005) the following year, with decrease in admission days from 54 to 18 per 100 patient years (P < 0.0005). In the same period, work absenteeism decreased and QOL improved significantly, with strong decline in fear of hypoglycemia. Conclusion: Sensor-augmented pump therapy in patients with T1D followed in specialized centers improves HbA(1c), fear of hypoglycemia, and QOL, whereas work absenteeism and admissions for acute diabetes complications decreased

Sustained Impact of Real-time Continuous Glucose Monitoring in Adults With Type 1 Diabetes on Insulin Pump Therapy: Results After the 24-Month RESCUE Study.

OBJECTIVE: In recent years, a growing number of people with type 1 diabetes gained access to real-time continuous glucose monitoring (rtCGM). Long-term benefits of rtCGM are unclear because of a lack of large studies of long duration. We evaluated whether real-world rtCGM use up to 24 months offered benefits, particularly in those living with impaired awareness of hypoglycemia (IAH). RESEARCH DESIGN AND METHODS: This 24-month, prospective, observational cohort study followed 441 adults with insulin pumps receiving full reimbursement for rtCGM. Forty-two percent had IAH. The primary end point was evolution of HbA1c, with secondary end points change in acute hypoglycemia complications, diabetes-related work absenteeism, and quality of life scores. Additionally, we evaluated whether people could achieve glycemic consensus targets during follow-up. RESULTS: After 24 months, HbA1c remained significantly lower compared with baseline (7.64% [60 mmol/mol] vs. 7.37% [57 mmol/mol], P < 0.0001). Sustained benefits were also observed for the score on the hypoglycemia fear survey and hypoglycemia-related acute complications irrespective of hypoglycemia awareness level. People with IAH had the strongest improvement, especially for severe hypoglycemia (862 events in the year before vs. 119 events per 100 patient-years in the 2nd year, P < 0.0001). Over 24 months, more people were able to meet hypoglycemia consensus targets at the expense of slightly fewer people achieving hyperglycemia consensus targets. Furthermore, the number of people with HbA1c <7% (<53 mmol/mol) without severe hypoglycemia events more than doubled (11.0% vs. 25.4%, P < 0.0001). CONCLUSIONS: Use of rtCGM led to sustained improvements in hypoglycemia-related glucose control over 24 months. Lower fear of hypoglycemia, fewer acute hypoglycemia-related events, and fewer diabetes-related days off from work were observed, particularly in those with IAH.status: publishe

Cost of respiratory syncytial virus-associated acute lower respiratory infection management in young children at the regional and global level: A systematic review and meta-analysis

Background. Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years. Methods. We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases. Results. We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [CI], 3265-3639) and €299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to €8591(95% CI, 8489-8692) and €2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event. Conclusions. Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with €4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately €4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society

Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir-experienced, NS5A treatment-naïve patients: Findings from two randomized trials.

Background &amp; aimsWe report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF)&nbsp;±&nbsp;ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens.MethodsThe RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12&nbsp;weeks of LDV/SOF or LDV/SOF&nbsp;+&nbsp;RBV. Compensated cirrhotic participants were randomized to LDV/SOF&nbsp;+&nbsp;RBV (12&nbsp;weeks) or LDV/SOF (24&nbsp;weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF&nbsp;+&nbsp;RBV (12&nbsp;weeks) or LDV/SOF (24&nbsp;weeks). Both studies used SVR at 12&nbsp;weeks post-treatment (SVR12) as the primary endpoint.ResultsIn the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF&nbsp;+&nbsp;RBV for 12&nbsp;weeks and 80-92% in cirrhotic participants treated with LDV/SOF&nbsp;+&nbsp;RBV for 12&nbsp;weeks or LDV/SOF for 24&nbsp;weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic n&nbsp;=&nbsp;1; GT1a n&nbsp;=&nbsp;5) and all attained SVR12, with no serious AEs or premature discontinuations.ConclusionsIn this SOF-experienced, NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved

Global disease burden estimates of respiratory syncytial virus-associated acute respiratory infection in older adults in 2015: A systematic review and meta-analysis

Respiratory syncytial virus.associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in older adults aged ≥65 years. We aimed to identify all studies worldwide investigating the disease burden of RSV-ARI in this population. We estimated the community incidence, hospitalization rate, and in-hospital case-fatality ratio (hCFR) of RSV-ARI in older adults, stratified by industrialized and developing regions, using data from a systematic review of studies published between January 1996 and April 2018 and 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burdens in older adults with RSV-ARI in the community and in hospitals for that year. We estimated the number of in-hospital deaths due to RSV-ARI by combining hCFR data with hospital admission estimates from hospital-based studies. In 2015, there were about 1.5 million episodes (95% confidence interval [CI], .3 million.6.9 million) of RSV-ARI in older adults in industrialized countries (data for developing countries were missing), and of these, approximately 14.5% (214 000 episodes; 95% CI, 100 000.459 000) were admitted to hospitals. The global number of hospital admissions for RSV-ARI in older adults was estimated at 336 000 hospitalizations (uncertainty range [UR], 186 000.614 000). We further estimated about 14 000 in-hospital deaths (UR, 5000.50 000) related to RSV-ARI globally. The hospital admission rate and hCFR were higher for those aged .65 years than for those aged 50.64 years. The disease burden of RSV-ARI among older adults is substantial, with limited data from developing countries. Appropriate prevention and management strategies are needed to reduce this burden

Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir-experienced, NS5A treatment-naïve patients: Findings from two randomized trials.

Background &amp; aimsWe report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF)&nbsp;±&nbsp;ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens.MethodsThe RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12&nbsp;weeks of LDV/SOF or LDV/SOF&nbsp;+&nbsp;RBV. Compensated cirrhotic participants were randomized to LDV/SOF&nbsp;+&nbsp;RBV (12&nbsp;weeks) or LDV/SOF (24&nbsp;weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF&nbsp;+&nbsp;RBV (12&nbsp;weeks) or LDV/SOF (24&nbsp;weeks). Both studies used SVR at 12&nbsp;weeks post-treatment (SVR12) as the primary endpoint.ResultsIn the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF&nbsp;+&nbsp;RBV for 12&nbsp;weeks and 80-92% in cirrhotic participants treated with LDV/SOF&nbsp;+&nbsp;RBV for 12&nbsp;weeks or LDV/SOF for 24&nbsp;weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic n&nbsp;=&nbsp;1; GT1a n&nbsp;=&nbsp;5) and all attained SVR12, with no serious AEs or premature discontinuations.ConclusionsIn this SOF-experienced, NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved