Cohort 2013 Four-Year Graduation Rates -- State Results

From September 2016-April 2017, Am Timan, Chad, experienced a large HEV outbreak in an urban setting with a limited impact in terms of morbidity and mortality. To better understand HEV epidemiology in this context, we estimated the seroprevalence of anti-HEV antibodies (IgM and IgG) and assessed the risk factors for recent HEV infections (positive anti-HEV IgM) during this outbreak

Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: the ASCOT trial.

BACKGROUND AND AIMS: Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment. METHODS: Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes. RESULTS: Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality. CONCLUSIONS: Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period

White Blood Cell Count and Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention in the Contemporary Era: Insights From the PARIS Study (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Registry).

Elevated white blood cell (WBC) count is associated with increased major adverse cardiovascular events (MACE) in the setting of acute coronary syndrome. The aim of this study was to evaluate whether similar associations persist in an all-comers population of patients undergoing percutaneous coronary intervention in the contemporary era. In the multicenter, prospective, observational PARIS study (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Registry), 4222 patients who underwent percutaneous coronary intervention in the United States and Europe between July 1, 2009, and December 2, 2010, were evaluated. The associations between baseline WBC and MACE (composite of cardiac death, stent thrombosis, spontaneous myocardial infarction, or target lesion revascularization) at 24-month follow-up were analyzed using multivariable Cox regression. Patients with higher WBC were more often younger, smokers, and with less comorbid risk factors compared with those with lower WBC. After adjustment for baseline and procedural characteristics, WBC remained independently associated with MACE (hazard ratio [HR] per 10(3) cells/μL increase, 1.05 [95% confidence intervals (CI), 1.02-1.09]; P=0.001), cardiac death (HR, 1.10 [95% CI, 1.05-1.17]; P&lt;0.001), and clinically indicated target revascularization (HR, 1.04 [95% CI, 1.00-1.09]; P=0.03) but not stent thrombosis (HR, 1.07 [95% CI, 0.99-1.16]; P=0.10) or spontaneous myocardial infarction (HR, 1.03 [95% CI, 0.97-1.09]; P=0.29). The association between WBC and MACE was consistent in acute coronary syndrome and non-acute coronary syndrome presentations (interaction P=0.15). Increased WBC is an independent predictor of MACE after percutaneous coronary intervention in a contemporary all-comers cohort. Further studies to delineate the underlying pathophysiologic role of elevated WBC across a spectrum of coronary artery disease presentations are warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00998127

Healthcare Resource Utilization Associated with Intermittent Oral Corticosteroid Prescribing Patterns in Asthma

Trung N Tran,1 Heath Heatley,2 Arnaud Bourdin,3 Andrew Menzies-Gow,4,5 David J Jackson,6 Ekaterina Maslova,5 Jatin Chapaneri,5 William Henley,2,7 Victoria Carter,2 Jeffrey Shi Kai Chan,2 Cono Ariti,2 John Haughney,8,9 David Price2,9 1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Department of Respiratory Diseases, PhyMedExp, University of Montpellier, Montpellier, France; 4Royal Brompton & Harefield Hospitals and School of Immunology & Microbial Sciences, King’s College London, London, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Guy’s Severe Asthma Centre, Guy’s and St Thomas’ Hospitals, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7Department of Health and Community Sciences University of Exeter Medical School, Exeter, UK; 8NHS Clinical Research Facilities, Glasgow, UK; 9Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email [email protected]: Oral corticosteroid (OCS) use for asthma is associated with considerable healthcare resource utilization (HCRU) and costs. However, no study has investigated this in relation to patterns of intermittent OCS prescription.Methods: This historical UK cohort study used primary care medical records, linked to Hospital Episode Statistics, from 2008 to 2019, of patients (≥ 4 years old) with asthma prescribed intermittent OCS. Patients were categorized by OCS prescribing pattern (one-off [single], less frequent [≥ 90-day gap] and frequent [< 90-day gap]) and matched 1:1 (by sex, age and index date) with people never prescribed OCS with/without asthma. HCRU (reported as episodes, except for length of hospital stay [days] and any prescription [records]) and associated costs were compared between intermittent OCS and non-OCS cohorts, and among intermittent OCS prescribing patterns.Results: Of 149,191 eligible patients, 50.3% had one-off, 27.4% less frequent, and 22.3% frequent intermittent OCS prescribing patterns. Annualized non-respiratory HCRU rates were greater in the intermittent OCS versus non-OCS cohorts for GP visits (5.93 vs 4.70 episodes, p < 0.0001), hospital admissions (0.24 vs 0.16 episodes, p < 0.0001), and length of stay (1.87 vs 1.58 days, p < 0.0001). In the intermittent OCS cohort, rates were highest in the frequent prescribing group for GP visits (7.49 episodes; p < 0.0001 vs one-off), length of stay (2.15 days; p < 0.0001) and any prescription including OCS (25.22 prescriptions; p < 0.0001). Mean per-patient non-respiratory related and all-cause HCRU-related costs were higher with intermittent OCS than no OCS (£ 3902 vs £ 2722 and £ 8623 vs £ 4929, respectively), as were mean annualized costs (£ 565 vs £ 313 and £ 1526 vs £ 634, respectively). A dose–response relationship existed; HCRU-related costs were highest in the frequent prescribing cohort (p < 0.0001).Conclusion: Intermittent OCS use and more frequent intermittent OCS prescription patterns were associated with increased HCRU and associated costs. Improved asthma management is needed to reduce reliance on intermittent OCS in primary care.Keywords: asthma, costs, healthcare resource utilization, intermittent, oral corticosteroid

Causes, Timing, and Impact of Dual Antiplatelet Therapy Interruption for Surgery (from the Patterns of Non-adherence to Anti-platelet Regimens In Stented Patients Registry).

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation for &lt;14 days. Of the study cohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents

Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID)

This is the final version. Available on open access from the NIHR Journals Library via the DOI in this recordData availability: All available data can be obtained from the corresponding author.BACKGROUND: Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. OBJECTIVE: To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. DESIGN: Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. SETTING: Primary and secondary mental health settings across the United Kingdom's National Health Service. PARTICIPANTS: One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. INTERVENTIONS: Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. MAIN OUTCOME MEASURES: Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. RESULTS: Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval -∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years -0.04 (95% confidence interval -0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. LIMITATIONS: The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. CONCLUSIONS: Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. FUTURE WORK: Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. TRIAL REGISTRATION: This trial is registered as ISRCTN13697710. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.National Institute for Health and Care Research (NIHR

Mortality beyond emergency threshold in a silent crisis– results from a population-based mortality survey in Ouaka prefecture, Central African Republic, 2020

Background The Central African Republic (CAR) suffers a protracted conflict and has the second lowest human development index in the world. Available mortality estimates vary and differ in methodology. We undertook a retrospective mortality study in the Ouaka prefecture to obtain reliable mortality data. Methods We conducted a population-based two-stage cluster survey from 9 March to 9 April, 2020 in Ouaka prefecture. We aimed to include 64 clusters of 12 households for a required sample size of 3636 persons. We assigned clusters to communes proportional to population size and then used systematic random sampling to identify cluster starting points from a dataset of buildings in each commune. In addition to the mortality survey questions, we included an open question on challenges faced by the household. Results We completed 50 clusters with 591 participating households including 4000 household members on the interview day. The median household size was 7 (interquartile range (IQR): 4—9). The median age was 12 (IQR: 5—27). The birth rate was 59.0/1000 population (95% confidence interval (95%-CI): 51.7—67.4). The crude and under-five mortality rates (CMR & U5MR) were 1.33 (95%-CI: 1.09—1.61) and 1.87 (95%-CI: 1.37–2.54) deaths/10,000 persons/day, respectively. The most common specified causes of death were malaria/fever (16.0%; 95%-CI: 11.0–22.7), violence (13.2%; 95%-CI: 6.3–25.5), diarrhoea/vomiting (10.6%; 95%-CI: 6.2–17.5), and respiratory infections (8.4%; 95%-CI: 4.6–14.8). The maternal mortality ratio (MMR) was 2525/100,000 live births (95%-CI: 825—5794). Challenges reported by households included health problems and access to healthcare, high number of deaths, lack of potable water, insufficient means of subsistence, food insecurity and violence. Conclusions The CMR, U5MR and MMR exceed previous estimates, and the CMR exceeds the humanitarian emergency threshold. Violence is a major threat to life, and to physical and mental wellbeing. Other causes of death speak to poor living conditions and poor access to healthcare and preventive measures, corroborated by the challenges reported by households. Many areas of CAR face similar challenges to Ouaka. If these results were generalisable across CAR, the country would suffer one of the highest mortality rates in the world, a reminder that the longstanding “silent crisis” continues

Effectiveness of initiating biologics in severe asthma patients with high steroid exposure

Peer reviewedPostprin

Characterization of patients in the International Severe Asthma Registry with high steroid exposure who did or did not initiate biologic therapy

Peer reviewedPostprin

Association between T2-related co-morbidities and effectiveness of biologics in severe asthma

Acknowledgments The authors thank Mr. Joash Tan (BSc, Hons), of the Observational and Pragmatic Research Institute (OPRI), and Ms Andrea Lim (BSc, Hons) of the Observational Pragmatic Research Institute (OPRI) for their editorial and formatting assistance that supported the development of this publication. Funding statement: This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. AstraZeneca UK LimitedPeer reviewe