Long-term clinical and cost-effectiveness of a therapist-supported online remote behavioural intervention for tics in children and adolescents: extended 12- and 18-month follow-up of a single-blind randomised controlled trial.

BACKGROUND: Little is known about the long-term effectiveness of behavioural therapy for tics. We aimed to assess the long-term clinical and cost-effectiveness of online therapist-supported exposure and response prevention (ERP) therapy for tics 12 and 18 months after treatment initiation. METHODS: ORBIT (online remote behavioural intervention for tics) was a two-arm (1:1 ratio), superiority, single-blind, multicentre randomised controlled trial comparing online ERP for tics with online psychoeducation. The trial was conducted across two Child and Adolescent Mental Health Services in England. Participants were recruited from these two sites, across other clinics in England, or by self-referral. This study was a naturalistic follow-up of participants at 12- and 18-month postrandomisation. Participants were permitted to use alternative treatments recommended by their clinician. The key outcome was the Yale Global Tic Severity Scale Total Tic Severity Score (YGTSS-TTSS). A full economic evaluation was conducted. Registrations are ISRCTN (ISRCTN70758207); ClinicalTrials.gov (NCT03483493). RESULTS: Two hundred and twenty-four participants were enrolled: 112 to ERP and 112 to psychoeducation. The sample was predominately male (177; 79%) and of white ethnicity (195; 87%). The ERP intervention reduced baseline YGTSS-TTSS by 2.64 points (95% CI: -4.48 to -0.79) with an effect size of -0.36 (95% CI: -0.61 to -0.11) after 12 months and by 2.01 points (95% CI: -3.86 to -0.15) with an effect size of -0.27 (95% CI -0.52 to -0.02) after 18 months, compared with psychoeducation. Very few participants (<10%) started new tic treatment during follow-up. The cost difference in ERP compared with psychoeducation was £304.94 (-139.41 to 749.29). At 18 months, the cost per QALY gained was £16,708 for ERP compared with psychoeducation. CONCLUSIONS: Remotely delivered online ERP is a clinical and cost-effective intervention with durable benefits extending for up to 18 months. This represents an efficient public mental health approach to increase access to behavioural therapy and improve outcomes for tics.

Estimating seasonal onsets and peaks of bronchiolitis with spatially and temporally uncertain data.

RSV bronchiolitis (an acute lower respiratory tract viral infection in infants) is the most common cause of infant hospitalizations in the United States (US). The only preventive intervention currently available is monthly injections of immunoprophylaxis. However, this treatment is expensive and needs to be administered simultaneously with seasonal bronchiolitis cycles in order to be effective. To increase our understanding of bronchiolitis timing, this research focuses on identifying seasonal bronchiolitis cycles (start times, peaks, and declinations) throughout the continental US using data on infant bronchiolitis cases from the US Military Health System Data Repository. Because this data involved highly personal information, the bronchiolitis dates in the dataset were "jittered" in the sense that the recorded dates were randomized within a time window of the true date. Hence, we develop a statistical change point model that estimates spatially varying seasonal bronchiolitis cycles while accounting for the purposefully introduced jittering in the data. Additionally, by including temperature and humidity data as regressors, we identify a relationship between bronchiolitis seasonality and climate. We found that, in general, bronchiolitis seasons begin earlier and are longer in the southeastern states compared to the western states with peak times lasting approximately 1 month nationwide.

Seasonal patterns of Asthma medication fills among diverse populations of the United States.

OBJECTIVE: Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity. METHODS: We conducted a retrospective cohort study of asthmatics 4-50 years of age and enrolled in three diverse health insurance plans. Seasonal patterns of medications were reported by monthly prescription fill rates per 1000 individuals with asthma from 1998 to 2013, and stratified by healthcare plan, sex, and age. RESULTS: There was a distinct and consistent seasonal fill pattern for all asthma medications. The lowest fill rate was observed in the month of July. Fills increased in the autumn and remained high throughout the winter and spring. Compared with the month of May with high medication fills, July represented a relative decrease of fills ranging from 13% (rate ratio, RR: 0.87, 95% confidence interval, 95%CI: 0.72-1.04) for the combination of inhaled corticosteroids (ICS) + long acting beta agonists (LABA) to 45% (RR: 0.55, 95%CI: 0.49-0.61) for oral corticosteroids. Such a seasonal pattern was observed each year across the 16-year study period, among healthcare plans, sexes, and ages. LABA containing control medication (ICS+LABA and LABA) fill rates were more prevalent in older asthmatics, while leukotriene receptor antagonists were more prevalent in the younger population. CONCLUSIONS: A seasonal pattern of asthma medication fill rates likely represents a reactive response to a loss of disease control and increased symptoms. Adherence to and consistent use of asthma medications among individuals who use medications in reaction to seasonal exacerbations might be a key component in reducing the risk of asthma exacerbations.

Online remote behavioural intervention for tics in 9- to 17-year-olds: the ORBIT RCT with embedded process and economic evaluation.

Background: Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective: To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design: Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting: Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants: Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions: Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome: Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results: Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval -0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms: Two serious, unrelated adverse events occurred in the control group. Limitations: We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion: Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work: Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration: This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.

It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 9­17 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy.

New mental health diagnoses in parents of infants admitted to a neonatal intensive care unit-a retrospective review of the Military Health System database.

OBJECTIVE: Studies suggest that parents of NICU infants are at increased risk of mental health disorders. We sought to characterize this risk using a large database. STUDY DESIGN: The Military Health System was used to retrospectively link records between parents and infants admitted to a NICU over 5 years and were matched to similar families without NICU exposure. The total study population included 35,012 infants. Logistic regression was used to estimate the association between NICU exposure and parental mental health diagnoses within 5 years of infant birth. RESULTS: Maternal NICU exposure was associated with incident diagnoses of depression (OR: 1.18-1.27, p < 0.0001), anxiety (OR: 1.06-1.18, p = 0.0151), alcohol/opiate dependence (OR: 1.29-1.52, p = 0.0079), and adjustment disorder (OR: 0.97-1.18, p = 0.0224). Paternal NICU exposure was associated with alcohol/opiate dependence (OR: 0.78-1.42, p = 0.0339). CONCLUSION: Parents of NICU infants are at risk of developing mental health disorders. Future work should identify characteristics that predict highest risk to develop effective interventions.

A penalized likelihood for multispecies occupancy models improves predictions of species interactions.

Multispecies occupancy models estimate dependence among multiple species of interest from patterns of co-occurrence, but problems associated with separation and boundary estimates can lead to unreasonably large estimates of parameters and associated standard errors when species are rarely observed at the same site or when data are sparse. In this paper, we overcome these issues by implementing a penalized likelihood, which introduces a small bias in parameter estimates in exchange for a potentially large reduction in variance. We compare parameter estimates obtained from both penalized and unpenalized multispecies occupancy models fit to simulated data that exhibit various degrees of separation and to a real-word data set of bird surveys with little apparent overlap between potentially interacting species. Our simulation results demonstrate that penalized multispecies occupancy models did not exhibit boundary estimates and produced lower bias, lower mean squared error, and improved inference relative to unpenalized models. When applied to real-world data, our penalized multispecies occupancy model constrained boundary estimates and allowed for meaningful inference related to the interactions of two species of conservation concern. To facilitate the use of our penalized multispecies occupancy model, the techniques demonstrated in this paper have been integrated into the unmarked package in R programing language.

Therapist-supported online remote behavioural intervention for tics in children and adolescents in England (ORBIT): a multicentre, parallel group, single-blind, randomised controlled trial.

BACKGROUND: Exposure and Response Prevention (ERP) is a form of behavioural therapy for tics; however, its effectiveness remains uncertain. We aimed to evaluate the effectiveness of internet-delivered, therapist-supported, and parent-assisted ERP for treatment of tics in children and young people with Tourette syndrome or chronic tic disorder. METHODS: This multicentre, parallel group, single-blind, randomised controlled trial was conducted across two study sites in England. Participants were recruited via 16 patient identification centres, two study sites in England (Nottingham and London), or online self-referral. Eligible participants were aged 9-17 years, had Tourette syndrome or chronic tic disorder, had not received behavioural therapy for tics in the past 12 months or were about to start, and had a Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTSS) of more than 15 or more than 10 if they had only motor or vocal tics. Patients were excluded if they had started or stopped medication for tics within the past 2 months; had current alcohol or substance dependence, psychosis, suicidality, anorexia nervosa, or suspected moderate to severe intellectual disability; or presented an immediate risk to self or others; or the parent or carer was unable to speak, read, or write in English. Eligible patients were randomly assigned (1:1) by masked outcome assessors to receive 10 weeks of online, remotely delivered, therapist-supported ERP or psychoeducation (active control). Outcome assessors, statisticians, health economists, the trial manager, and the chief investigator were masked to group allocation. Patients were not directly informed of their allocation, but this could be established from the content once treatment commenced and the patients were not, therefore, considered masked to treatment. The primary outcome was YGTSS-TTSS 3 months after randomisation, and analysis was done in all randomised patients for whom data were available for each timepoint and outcome. Safety analysis was by intention to treat. Longer term follow-up is ongoing. This trial is registered with ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493). FINDINGS: Between May 8, 2018, and Sept 30, 2019, we assessed 445 candidates for inclusion in the study. 221 potential participants were excluded (90 did not meet inclusion criteria, 84 declined to participate, and 47 unable to contact family). 224 participants were enrolled and randomly assigned to ERP (n=112) or psychoeducation (n=112). The enrolled patients were mostly male (n=177; 79%) and of White ethnicity (n=195; 87%). 11 patients were lost to follow-up 3 months after randomisation in the ERP group, compared with 12 patients in the psychoeducation group. Mean YGTSS-TTSS at 3 months after randomisation was 23·9 (SD 8·2) in the ERP group and 26·8 (7·3) in the psychoeducation group. The mean total decrease in YGTSS-TTSS at 3 months was 4·5 (16%, SD 1·1) in the ERP group versus 1·6 (6%, 1·0) in the psychoeducation group. The estimated mean difference in YGTSS-TTSS change between the groups adjusted for baseline and site was -2·29 points (95% CI -3·86 to -0·71) in favour of ERP, with an effect size of -0·31 (95% CI -0·52 to -0·10). Two serious adverse events occurred (one collapse and one tic attack), both in the psychoeducation group, neither of which were related to study treatment. INTERPRETATION: ERP is an effective behavioural therapy for tics. Remotely delivered, online ERP with minimal therapist contact time represents an efficient public mental health approach to improve access to behavioural therapy for tics in children and adolescents. FUNDING: National Institute for Health Research and Health and Technology Assessment.

Modeling Bronchiolitis Incidence Proportions in the Presence of Spatio-Temporal Uncertainty.

Bronchiolitis (inflammation of the lower respiratory tract) in infants is primarily due to viral infection and is the single most common cause of infant hospitalization in the United States. To increase epidemiological understanding of bronchiolitis (and, subsequently, develop better prevention strategies), this research analyzes data on infant bronchiolitis cases from the U.S. Military Health System between the years 2003-2013 in Norfolk, Virginia, USA. For privacy reasons, child home addresses, birth dates, and diagnosis dates were randomized (jittered) creating spatio-temporal uncertainty in the geographic location and timing of bronchiolitis incidents. Using spatio-temporal point patterns, we created a modeling strategy that accounts for the jittering to estimate and quantify the uncertainty for the incidence proportion (IP) of bronchiolitis. Additionally, we regress the IP onto key covariates including pollution where we adequately account for uncertainty in the pollution levels (i.e., covariate uncertainty) using a land use regression model. Our analysis results indicate that the IP is positively associated with sulfur dioxide and population density. Further, we demonstrate how scientific conclusions may change if various sources of uncertainty (either spatio-temporal or covariate uncertainty) are not accounted for. Code submitted with this article was checked by an Associate Editor for Reproducibility and is available as an online supplement.

Incident cardiovascular disease in patients diagnosed with multiple sclerosis: A multi-database study.

BACKGROUND: Recent data on rates of cardiovascular disease (CVD) in patients after MS diagnosis are sparse. OBJECTIVE: To describe incident CVD in MS patients after diagnosis compared with a matched non-MS population. METHODS: We conducted a matched cohort study in two separate electronic medical databases, the United States Department of Defense military health care system and the United Kingdom's Clinical Practice Research Datalink GOLD. The study population included all patients with a first recorded diagnosis of MS and no history of CVD or selected measurable comorbidities associated with CVD and matched non-MS patients who were also free of CVD and the CVD associated comorbidities. We identified incident CVD outcomes first recorded after the MS diagnosis / matched date and calculated incidence rates and incidence rate ratios by type of CVD. RESULTS: Rates of venous thromboembolism and peripheral vascular disease were 2-fold higher among MS than non-MS patients in both databases and the risk of myocardial infarction was 2.5 times higher among female MS patients compared with non-MS females in both databases. Other CVD outcomes were not consistent between databases. CONCLUSION: MS patients in the UK and the US have increased risk of venous thromboembolism and peripheral vascular disease. The risk of myocardial infarction is increased among female MS patients.

Comorbidities and Prescribed Medications in Patients With or Without Dry Eye Disease: A Population-Based Study.

PURPOSE: To assess the proportion of comorbidities in patients with dry eye disease (DED) compared with matched patients without DED in a comprehensive US population. DESIGN: Retrospective case-control study. METHODS: Healthcare records for insurance claims data, detailing medical services incurred by military personnel and their families and dependents in military and civilian facilities across the United States from January 1, 2003, to March 31, 2015, were obtained from the Department of Defense (DOD) Military Health System (MHS). Diagnostic and procedural codes related to DED from selected International Classification of Diseases, Ninth Revision (ICD-9) Current Procedural Terminology codes and prescriptions for cyclosporine A ophthalmic emulsion were used to identify patients with newly diagnosed and prevalent DED in the MHS database. Age, sex, and geographically matched patients without DED were also identified from healthcare claims records. Medication use and comorbidities in these patient populations were assessed and compared. RESULTS: In both the newly diagnosed and prevalent DED samples, the most common comorbidities were hypertension, cataracts, thyroid disease, type 2 diabetes, and glaucoma. All comorbidities were significantly higher in the DED vs non-DED groups (P < .001). Medication use (including, but not limited to, ophthalmic agents and drugs to treat comorbidities) was also significantly higher in the DED than in the non-DED groups (P < .001). CONCLUSIONS: The high proportions of patients with DED with a range of comorbidities and prescribed medications highlight the need for a multidisciplinary approach to the management of these patients.

Dry eye disease ranking among common reasons for seeking eye care in a large US claims database.

OBJECTIVES: Dry eye disease (DED) is a complex multifactorial condition of the ocular surface characterized by symptoms of ocular discomfort, irritation, and visual disturbance. Data previously reported from this study showed an increase in prevalence and incidence of DED with age and over time. The objective of this study was to compare the ranking of DED prevalence among other ocular conditions that led patients to seek eye care. METHODS: In this population-based study using the US Department of Defense Military Health System claims database of >9.7 million beneficiaries, indicators of DED and other ocular conditions were analyzed over time. The overall prevalence (2003-2015) and annual incidence (2008-2012) of DED and other ocular conditions were estimated using an algorithm based on two independent indicators derived from selected diagnostic and procedure codes and prescriptions for cyclosporine ophthalmic emulsion for DED and diagnostic codes for the indicators of other common ocular conditions. RESULTS: In 2003-2015, the most common ocular conditions were disorders of refraction and accommodation (25.84%), cataracts (17.14%), glaucoma (7.27%), disorders of the conjunctiva (6.76%), other retinal disorders (5.94%), and DED (5.28%). DED was the fifth most prevalent ocular condition in women (7.78%) and ninth most prevalent in men (2.96%). In 2012, DED had the third highest annual incidence (0.87%), behind disorders of refraction/accommodation (1.87%) and cataracts (1.50%). CONCLUSION: This study provided further epidemiologic evidence for DED as a commonly occurring condition that drives patients to seek treatment.

Multi-database study of multiple sclerosis: identification, validation and description of MS patients in two countries.

OBJECTIVE: To describe the resources and methods used to identify and validate multiple sclerosis (MS) and match non-MS patients in each of the two databases, and to characterize their demographics, comorbidities and concomitant medications. METHODS: This study was conducted in two separate electronic medical databases, the United States Department of Defense (DOD) military health care system and the United Kingdom's Clinical Practice Research Datalink (CPRD) GOLD. We identified patients with a first recorded diagnosis of MS in 2001-2016 (CPRD) or 2004-2017 (DOD) and matched non-MS patients using algorithms appropriate to each database. We describe patient symptoms, comorbidities, and medication use at the time of the MS diagnosis and compared them to the non-MS cohort. RESULTS: We identified 8695 patients with MS and 86,934 matched non-MS patients in the DOD database and 6932 patients with MS and 68,526 matched non-MS patients in CPRD GOLD. Most MS patients were female (around 70%) and were diagnosed before age 60 (88%). MS patients had higher prevalence of depression and other psychiatric conditions at MS diagnosis compared to non-MS patients. Epilepsy, fractures and infections were also more common. MS patients had many expected symptoms and treatments documented in their records prior to the MS diagnosis. CONCLUSION: These results are consistent between the two databases, as well as with previous studies of MS. Future analyses of these patients' experience after MS diagnosis will provide valuable insights into disease and treatment patterns in relation to risk of chronic diseases and mortality.

Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System.

PURPOSE: To assess overall prevalence, annual prevalence, and incidence of dry eye disease (DED) in a large, representative population in the United States. DESIGN: Prevalence and incidence study. METHODS: Retrospective analysis using the Department of Defense (DOD) Military Health System (MHS) data on beneficiary medical claims from United States DOD military and civilian facilities, January 1, 2003 through March 31, 2015. PATIENT POPULATION: Using an algorithm, medical diagnostic codes indicative of DED and prescriptions for cyclosporine ophthalmic emulsion identified a DED population from 9.7 million MHS beneficiaries (DOD service members, retirees, and dependents, aged 2-80+ years). MAIN OUTCOME MEASURES: DED overall prevalence (2003-2015), annual prevalence (2005-2012), and annual incidence (2008-2012) stratified by sex, age group, and International Statistical Classification of Diseases and Related Health Problems, Ninth Revision diagnosis code grouping. RESULTS: DED prevalence was 5.28% overall, 7.78% among female beneficiaries, 2.96% among male beneficiaries and increased with age from 0.20% for ages 2-17 years, to 11.66% for individuals aged 50+ years. Annual prevalence increased from 0.8% to 3.0% overall, from 1.4% to 4.5% in female beneficiaries, and from 0.3% to 1.6% in male beneficiaries. Annual prevalence increased across age groups starting at age 18-39, 0.1%-0.6%, to age 50+, 1.8%-6.0%. Annual incidence increased from 0.6% to 0.9% overall, from 0.8% to 1.2% in female beneficiaries, and from 0.3% to 0.6% in male beneficiaries. Across age groups, annual incidence increased starting at age 18-39 (0.2%-0.3%), to age 50+ (1.0%-1.6%). CONCLUSIONS: DED overall prevalence, annual prevalence, and incidence were found to increase over time for all demographics. These findings highlight the continued importance of research and therapeutic development for this common condition.

Comparative safety and effectiveness of dabigatran vs. rivaroxaban and apixaban in patients with non-valvular atrial fibrillation: a retrospective study from a large healthcare system.

AIMS: We used the US Department of Defense Military Health System database to compare the safety and effectiveness of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) initiating dabigatran vs. rivaroxaban or apixaban. METHODS AND RESULTS: Two cohorts of adults with NVAF, newly initiated on standard-dose DOAC, were identified based on clinical approval dates: July 2011-June 2016 for dabigatran (150 mg b.i.d.) or rivaroxaban (20 mg QD) and January 2013-June 2016 for dabigatran (150 mg b.i.d.) or apixaban (5 mg b.i.d.). Propensity score matching (1:1) identified two well-balanced cohorts (dabigatran vs. rivaroxaban n = 12 763 per treatment group; dabigatran vs. apixaban n = 4802 per treatment group). In both cohorts, baseline characteristics and follow-up duration were similar between treatment groups. Patients newly initiating dabigatran had significantly lower risk of major bleeding vs. rivaroxaban [2.08% vs. 2.53%; hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.70-0.97; P = 0.018], while stroke risk was similar (0.60% vs. 0.78%; HR 0.77, 95% CI 0.57-1.04; P = 0.084). The dabigatran vs. apixaban cohort analysis found no differences in risk of major bleeding (1.60% vs. 1.21%; HR 1.37, 95% CI 0.97-1.94; P = 0.070) or stroke (0.44% vs. 0.35%; HR 1.26, 95% CI 0.66-2.39; P = 0.489). CONCLUSION: Among NVAF patients newly initiated on standard-dose DOAC therapy in this study, dabigatran was associated with significantly lower major bleeding risk vs. rivaroxaban, and no significant difference in stroke risk. For dabigatran vs. apixaban, the reduced sample size limited the ability to draw definitive conclusions.

Investigating a therapist-guided, parent-assisted remote digital behavioural intervention for tics in children and adolescents-'Online Remote Behavioural Intervention for Tics' (ORBIT) trial: protocol of an internal pilot study and single-blind randomised controlled trial.

INTRODUCTION: Tourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms. METHODS AND ANALYSIS: This parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9-17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02). ETHICS AND DISSEMINATION: The findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079). TRIAL REGISTRATION NUMBERS: ISRCTN70758207 and NCT03483493; Pre-results.

Repeat Hospitalizations Predict Mortality in Patients With Heart Failure.

INTRODUCTION: Heart failure (HF) affects more than 5.1 million Americans and is projected to increase. Understanding the relationship between hospitalization and mortality can help to guide clinical management. The aim of the study is to evaluate the impact of repeat HF hospitalizations on all-cause mortality and to determine risk variables related to patient mortality. MATERIALS AND METHODS: Using administrative data from the Military Health System, a cohort of patients with an index admission for HF between 2007 and 2011 was identified. HF hospitalizations were defined as any hospital claim with an International Classification of Diseases, Ninth Revision diagnosis of 428.xx in the primary diagnosis field over the 7-year study period (2007-2013). Patients were subsequently categorized based on total number of HF hospitalizations. A multivariate Cox regression model, adjusting for age, sex, and comorbidities, was used to estimate hazard ratios. Kaplan-Meier survival curves were constructed based on the frequency of HF hospitalizations. RESULTS: Of the 51,286 patients admitted for HF, 54.7% were male with a mean (SD) age of 76.3 (10.8) years, and 29,714 died during 135,211 person-years of follow-up. Mean survival time was 2.6, 1.8, 1.5, and 1.3 years after the first, second, third, and fourth hospitalization, respectively. The mortality rate of patients at 30 days and 1 year postindex HF hospitalization was 7.4% and 27.3%, respectively. A history of dementia and chronic kidney disease without dialysis decreased overall survival. CONCLUSIONS: Repeat HF hospitalizations remain a strong predictor of mortality for existing patients with HF. As a result, clinicians and patients can individualize the optimal treatment strategy and resources on the basis of the suspected prognosis.

The impact of temperature and relative humidity on spatiotemporal patterns of infant bronchiolitis epidemics in the contiguous United States.

Infant bronchiolitis is primarily due to infection by respiratory syncytial virus (RSV), which is highly seasonal. The goal of the study is to understand how circulation of RSV is impacted by fluctuations in temperature and humidity in order to inform prevention efforts. Using data from the Military Health System (MHS) Data Repository (MDR), we calculated rates of infant bronchiolitis for the contiguous US from July 2004 to June 2013. Monthly temperature and relative humidity were extracted from the National Climate Data Center. Using a spatiotemporal generalized linear model for binomial data, we estimated bronchiolitis rates and the effects of temperature and relative humidity while allowing them to vary over location and time. Our results indicate a seasonal pattern that begins in the Southeast during November or December, then spreading in a Northwest direction. The relationships of temperature and humidity were spatially heterogeneous, and we find that climate can partially account for early onset or longer epidemic duration. Small changes in climate may be associated with larger fluctuations in epidemic duration.

Predictors of Revision Surgery After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Arthroscopically assisted anterior cruciate ligament (ACL) reconstruction is a common orthopaedic procedure. Graft failure after reconstruction remains a devastating complication, often requiring revision surgery and less aggressive or modified rehabilitation. Worse functional and patient-reported outcomes are reported compared with primary reconstruction. Moreover, both rates and risk factors for revision are variable and inconsistent within the literature. PURPOSE: To determine the rate of revision surgery after ACL reconstruction in a large cohort of patients, to assess the influence of patient characteristics on the odds of revision, and to compare revision rates between active-duty military members and non-active-duty beneficiaries. STUDY DESIGN: Descriptive epidemiology study. METHODS: Using administrative data from the Military Health System, a retrospective study was designed to characterize the rate of ACL revision surgery among patients treated within a military facility. All patients ≥18 years at the time of ACL reconstruction were identified using the American Medical Association Current Procedural Terminology (CPT) for ACL reconstruction (CPT code 29888) over 7 years (2005-2011). Revision ACL reconstructions were identified as having ≥2 ACL reconstruction procedure codes on the ipsilateral knee at least 90 days apart. Univariate analysis was performed to calculate odds ratios (ORs) for demographic, perioperative medication use, and concomitant procedure-related risk factors. A multivariate logistic regression model determined risk covariates in the active-duty cohort. RESULTS: The study population consisted of 17,164 ACL reconstructions performed among 16,336 patients, of whom 83.3% were male with a mean ± SD age of 28.9 ± 7.6 years for the nonrevision group, and was predominantly active duty (89.2%). Patients undergoing ACL reconstruction on both knees only contributed their index knee for analyses. There were 587 patients who underwent revision surgery, corresponding to an overall revision rate of 3.6%. The median time from the index surgery to revision surgery was 500 days (interquartile range, 102-2406 days). Revision rates were higher in the active-duty cohort as compared with non-active-duty beneficiaries (3.8% vs 1.8%, respectively; OR, 2.14; 95% CI, 1.49-3.07). Based on multivariate logistic regression in the active-duty cohort, age ≥35 years (OR, 0.44; 95% CI, 0.33-0.58) and concomitant meniscal repair (OR, 0.69; 95% CI, 0.53-0.91) were found to be protective with regard to the odds of revision surgery. Perioperative medication use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR, 1.33; 95% CI, 1.12-1.58; number needed to harm [NNH], 100) and COX-2 inhibitors (OR, 1.31; 95% CI, 1.04-1.66; NNH, 333) was associated with increased odds of revision surgery. No significant findings were detected among sex, race, nicotine use, body mass index, or other concomitant procedures of interest. CONCLUSION: In this large cohort study, the rate of revision ACL reconstruction was 3.6%, which is consistent with the existing literature. Increased odds of revision surgery among active-duty personnel were associated with the perioperative use of NSAIDs and COX-2 inhibitors. Age ≥35 years and concomitant meniscal repair were found to be protective against ACL revision.

The Prevalence of Symptomatic Deep Venous Thrombosis and Pulmonary Embolism After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Arthroscopically assisted anterior cruciate ligament (ACL) reconstruction is a common orthopaedic procedure. The incidence and risk factors of venous thromboembolism (VTE) after ACL reconstruction remain unclear. PURPOSE: To define the incidence of VTE after ACL reconstruction and identify associated risk factors in a large cohort of patients. STUDY DESIGN: Descriptive epidemiological study. METHODS: All patients aged ≥18 years who underwent ACL reconstruction between 2005 and 2011 were identified from the Department of Defense Medical Data Repository. The prevalence of VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE), within 3 months of ACL reconstruction was queried. Univariate analyses were performed to define odds ratios (ORs) for demographic, medication use, and procedural-related risk factors. RESULTS: A total of 87 VTE events (0.53% [95% CI, 0.42%-0.65%]) occurred after 16,558 ACL reconstructions performed on 15,767 patients. DVT was documented after 55 procedures and PE after 35 procedures. Three patients were documented to have both DVT and PE within the study period. The odds of VTE increased in patients aged ≥35 years (OR, 1.96 [95% CI, 1.27-3.04]; P = .003). Nicotine history increased the odds of DVT (OR, 1.99 [95% CI, 1.15-3.43]; P = .014). Concomitant high tibial osteotomy (HTO) increased the odds of PE (OR, 18.31 [95% CI, 2.4-139.6]; P = .005), whereas concomitant posterior cruciate ligament (PCL) reconstruction increased the odds of both VTE (OR, 3.43 [95% CI, 1.07-11.2]; P = .38) and DVT (OR, 5.57 [95% CI, 1.71-18.14]; P = .004). Nonsteroidal drug use was associated with decreased odds for VTE and DVT (OR, 0.44 [95% CI, 0.28-0.70]; P < .001 and OR, 0.38 [95% CI, 0.22-0.69]; P < .001, respectively). Anticoagulants were associated with increased odds for VTE, DVT, and PE (OR, 98.32 [95% CI, 61.63-156.86]; P < .001; OR, 111.93 [95% CI, 63.95-195.92]; P < .001; and OR, 47.84 [95% CI, 22.55-101.52]; P < .001, respectively). No detectible difference in odds was found for sex, body mass index, or aspirin or cyclooxygenase-2 inhibitor use. CONCLUSION: The incidence of VTE after ACL reconstruction in this large population was low. Increased odds of VTE was identified in patients aged ≥35 years with a history of nicotine use, anticoagulant use, concomitant HTO, or concomitant PCL reconstruction. Controlled studies are necessary to determine the efficacy of chemoprophylaxis and to develop evidence-based clinical practice guidelines to minimize VTE after ACL reconstruction.