Clinical burden of severe respiratory syncytial virus infection during the first 2 years of life in children born between 2000 and 2011 in Scotland.

National data from Scotland (all births from 2000 to 2011) were used to estimate the burden associated with respiratory syncytial virus hospitalisation (RSVH) during the first 2 years of life. RSVHs were identified using the International Classification of Diseases 10th Revision codes. Of 623,770 children, 13,362 (2.1%) had ≥ 1 RSVH by 2 years, with the overall rate being 27.2/1000 (16,946 total RSVHs). Median age at first RSVH was 137 days (interquartile range [IQR] 62-264), with 84.3% of admissions occurring by 1 year. Median length of stay was 2 (IQR 1-4) days and intensive care unit (ICU) admission was required by 4.3% (727) for a median 5 (IQR 2-8) days. RSVHs accounted for 6.9% (5089/73,525) of ICU bed days and 6.2% (64,395/1,033,121) of overall bed days (5370/year). RSVHs represented 8.5% (14,243/168,205) of all admissions between October and March and 14.2% (8470/59,535) between December and January. RSVH incidence ranged from 1.7 to 2.5%/year over the study period. Preterms (RSVH incidence 5.2%), and those with congenital heart disease (10.5%), congenital lung disease (11.2%), Down syndrome (14.8%), cerebral palsy (15.5%), cystic fibrosis (12.6%), and neuromuscular disorders (17.0%) were at increased risk of RSVH.Conclusions: RSV causes a substantial burden on Scottish paediatric services during the winter months.What is known:• Respiratory syncytial virus (RSV) is a leading cause of childhood hospitalisation.What is new:• This 12-year study is the first to estimate the burden of RSV hospitalisation (RSVH) in Scotland and included all live births from 2000 to 2011 and followed > 600,000 children until 2 years old.• The overall RSVH rate was 27.2/1000 children, with 2.1% being hospitalised ≥ 1 times.• RSVHs accounted for 6.2% of all inpatient bed days, which rose to 14.2% during the peak months of the RSV season (December-January), equating to over 1400 hospitalisations and nearly 5500 bed days each year.

Trends in use of and complications from intrauterine contraceptive devices and tubal ligation or occlusion.

BACKGROUND: Long-acting reversible contraceptives such as intrauterine devices (IUDs) are highly effective in preventing pregnancy, cost effective, and increasing in popularity. It is unclear whether changes in IUD use are associated with changes in rates of irreversible tubal sterilization. In this analysis, we evaluate changes in rates of tubal sterilization, insertion of copper or levonorgestrel (LNG) IUDs, and related complications over time. METHODS: Data were obtained from a retrospective claims database (OptumTM ClinformaticsTM Data Mart) of women aged 15 to 45 years who underwent insertion of copper or LNG IUD or tubal sterilization between 1/1/2006 and 12/31/2011. Outcomes of interest included annual rates of insertion or sterilization and annual rates of potential complications and side effects. RESULTS: The number of women included in the analysis each year ranged from 1,870,675 to 2,016,916. Between 2006 and 2011, copper IUD insertion claim rates increased from 0.18 to 0.25% and LNG IUD insertion claim rates increased from 0.63 to 1.15%, while sterilization claims decreased from 0.78 to 0.66% (P < 0.0001 for all comparisons). Increases in IUD insertion were apparent in all age groups; decreases in tubal sterilization occurred in women aged 20 to 34 years. The most common side effects and complications were amenorrhea (7.36-11.59%), heavy menstrual bleeding (4.85-15.69%), and pelvic pain (11.12-14.27%). Significant increases in claims of certain complications associated with IUD insertion or sterilization were also observed. CONCLUSION: Between 2006 and 2011, a decrease in sterilization rates accompanied an increase in IUD insertion rates, suggesting that increasing numbers of women opted for reversible methods of long-term contraception over permanent sterilization.

Cranial Nerve Anatomy Using a Modular and Multimodal Radiologic Approach.

Introduction: Medical students often struggle with learning cranial nerve anatomy. Typically, cranial nerve anatomy is taught using didactic lectures and textbook illustrations, often leaving students frustrated. Methods: We developed a multimodal radiologic approach to teaching cranial nerve anatomy. First, 150 students were presented with carefully curated preclass material from which to prepare. Next, they received a didactic lecture that was recorded for them to revisit on their own time. Last, students worked in groups in a lab setting with expert radiologists to identify the cranial nerves and related anatomy and learn about some basic pathophysiology. We used a pretest and posttest to examine the effectiveness of our teaching methods and a survey to measure students' satisfaction. Results: Student knowledge of cranial nerve structure was significantly improved after our module, with quiz scores increasing from 4.6 to 6.8 out of 9.0 (p < .001). In addition, students reported feeling more confident in their knowledge of the material and offered high satisfaction scores. Discussion: The breadth of knowledge covered during the preclinical training years continues to expand despite stable or even contracted durations of training, requiring knowledge to be delivered in an ever more efficient manner. Ultimately, the multimodal pedagogy used by our resource leads to students who are more confident and engaged in their learning, resulting in increased knowledge.

A survey of care pathway and health-related quality of life impact for children with central precocious puberty.

Objective: To describe the timeline to diagnosis for children with central precocious puberty (CPP) and evaluate their psychosocial and health-related quality of life (HRQoL).Methods: A cross-sectional survey was used to prospectively collect data from caregivers, recruited via the MAGIC Foundation, of children with CPP. The control (non-CPP) group was recruited from a national panel of parents/caregivers. After completing a screening survey, respondents completed a burden of illness survey. Respondents in both groups completed the Pediatric Quality of Life Inventory (PedsQL) and Patient-Reported Outcomes Measurement Information System (PROMIS) peer relationship instruments.Results: Responses from 142 caregivers of children with and 300 without CPP were assessed. Mean time to treatment after a child's visit to the pediatric endocrinologist was 220 days and time from onset of symptoms to initiating treatment was approximately 2 years. Responses to HRQoL inventories were all lower in children with CPP versus non-CPP. Adjusted mean (± standard error) PedsQL total (65.3 ± 1.8 versus 75.7 ± 1.2), Psychosocial Health Summary (62.4 ± 1.8 versus 73.4 ± 1.2), and Physical Health Summary (70.7 ± 2.2 versus 79.9 ± 1.5) scores were significantly lower (p < .01) in CPP versus non-CPP group. PROMIS peer relationship T score (± standard error) was numerically lower for the CPP versus non-CPP group (45.4 ± 1.0 versus 47.4 ± 0.7, p = .11).Conclusions: In clinical practice, there is a longer than expected delay between CPP symptom onset and referral to an endocrinologist and ultimate treatment. Children with CPP experience a substantial disease burden with a significant impact on emotional, social, and physical functioning compared with children without CPP.

Treatment patterns, health resource utilization and costs among central precocious puberty patients treated with leuprolide or histrelin: an examination of the commercial and Medicaid populations.

Aims: To compare treatment duration, healthcare resource utilization (HRU), and direct healthcare costs between patients with central precocious puberty (CPP) treated with leuprolide or histrelin, and between patients with Medicaid or commercial insurance. This information is important as it affects treatment choice and outcomes.Materials and methods: This retrospective cohort study identified commercial and Medicaid-insured CPP patients ≤12-years-old who were diagnosed between 1 January 2010 and 30 September 2014 and had ≥1 prescription for leuprolide or histrelin (first prescription = index date). Treatment patterns were measured for the duration of available data; whereas, all-cause and disease-monitoring HRU and all-cause costs were compared between treatment groups for the year following treatment initiation. Multivariable analysis was used to adjust healthcare costs for differences in baseline patient characteristics.Results: A total of 1,177 commercially-insured (907 leuprolide and 270 histrelin) and 658 Medicaid-insured (613 leuprolide and 45 histrelin) patients were identified. Mean age at treatment initiation ranged from 7.5-8.5-years-old, 11.1-20.5% of patients were male, and the mean treatment duration was over one year. Commercially-insured patients treated with histrelin used more services in general than those treated with leuprolide but had fewer office visits. Healthcare service utilization was similar between Medicaid-insured treatment groups. In both payer populations, costs were similar.Limitations: The number of Medicaid-insured patients who received a histrelin implant was low, and this may make the findings more sensitive to influence by outliers.Conclusions: Mean overall healthcare costs were similar between CPP patients treated with leuprolide and those treated with histrelin. Medicaid patients generally received less testing and were less likely to receive specialist care. Patients treated with histrelin had fewer office visits but also had a shorter overall treatment.

Association between respiratory syncytial virus hospitalization in infancy and childhood asthma.

INTRODUCTION: Respiratory syncytial virus infection in early childhood has been linked to longer-term respiratory morbidity; however, debate persists around its impact on asthma. The objective was to assess the association between respiratory syncytial virus hospitalization and childhood asthma. METHODS: Asthma hospital admissions and medication use through 18 years were compared in children with (cases) and without (controls) respiratory syncytial virus hospitalization in the first 2 years of life. All children born in National Health Service Scotland between 1996 and 2011 were included. RESULTS: Of 740 418 children (median follow-up: 10.6 years), 15 795 (2.1%) had a respiratory syncytial virus hospitalization at ≤2 years (median age: 143 days). Asthma hospitalizations were three-fold higher in cases than controls (8.4% vs 2.4%; relative risk: 3.3, 95% confidence interval [CI]: 3.1-3.5; P < .0001) and admission rates were four-fold higher (193.2 vs 46.0/1000). Cases had two-fold higher asthma medication usage (25.5% vs 14.7%; relative risk: 1.7, 95% CI: 1.7-1.8; P < .0001) and a three-fold higher rate of having both an asthma admission and medication (4.8% vs 1.5%; relative risk 3.1, 95% CI: 2.9-3.3; P < .0001). Admission rates and medication use remained significantly (P < .001) higher for cases than controls throughout childhood (admissions: ≥2-fold higher; medication: ≥1.5-fold higher). Respiratory syncytial virus hospitalization was the most significant risk factor for asthma hospitalizations±medication use (odds ratio: 1.9-2.8; P < .001). CONCLUSIONS: Respiratory syncytial virus hospitalization was associated with significantly increased rates and severity of asthma throughout childhood, which has important implications for preventive strategies.

Health Care Utilization and Economic Burden in Patients with Central Precocious Puberty: An Assessment of the Commercially Insured and Medicaid Populations.

BACKGROUND: Central precocious puberty (CPP), early onset of puberty caused by the premature activation of the hypothalamic-pituitary-gonadal axis, is a rare disease affecting children of both sexes. There is limited evidence that quantifies the economic burden of CPP. OBJECTIVE: To characterize the health care resource utilization (HRU) and costs among patients with CPP who were treated with gonadotropinreleasing hormone (GnRH) agonists, for those insured commercially and with Medicaid. METHODS: Eligible CPP patients for this retrospective cohort analysis were aged ≤ 12 years; were diagnosed between January 1, 2010, and September 30, 2014; and had at least 1 prescription for an FDA-approved GnRH agonist: leuprolide or histrelin (first prescription = index date). CPP patients had to be continuously enrolled in the MarketScan Commercial or Medicaid Database for at least 12 months before and after the index date. Control patients were randomly selected from all eligible non-CPP patients and N:1 matched on demographic characteristics with up to 20 controls per case. Clinical comorbidities, HRU, and costs were compared between study cohorts. Health care costs were examined via multivariable analysis to adjust for baseline differences between patients and controls. Treatment patterns among CPP patients were also characterized. RESULTS: There were 1,236 CPP patients and 24,206 controls with commercial insurance and 673 CPP patients and 11,965 controls with Medicaid insurance who met the inclusion criteria. Across payers, the mean age of CPP patients ranged from 7.6 years (Medicaid) to 8.5 (commercial), and 80%-87% were female. The mean observed duration (SD) of treatment with any approved GnRH agonist was 1.51 (0.98) years for commercial patients and 1.22 (1.04) for Medicaid patients. The mean age of discontinuation among patients who ceased GnRH agonist treatment ranged from 8.7 to 9.6 years. In the first year post-index, CPP patients had a greater number of unique diagnosis codes, unique medications, and comorbid conditions than controls. They also had significantly higher all-cause and diseasemonitoring related HRU. After adjusting for baseline characteristics, CPP patients with Medicaid insurance spent 6.42 times more ($16,768 [$31,460] vs. $2,610 [$4,897]), and patients with commercial insurance spent 12.25 times more ($19,940 [$20,132] vs. $1,628 [$1,645]) on health care in the year following treatment initiation than matched controls. CONCLUSIONS: Patients with CPP have substantially more comorbidities and greater HRU and costs than their non-CPP peers. DISCLOSURES: All funding for this study was provided by AbbVie, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Soliman and Grubb are employed by AbbVie and hold stock in AbbVie. Bonafede and Nelson are employed by IBM Watson Health, which received funding from AbbVie to conduct this study. Klein is a paid consultant of AbbVie but was not compensated for any work on development of this manuscript for publication. Portions of this work were presented at Pediatric Academic Societies (PAS) 2018 Meeting, May 5-8, 2018, in Toronto, Canada, as a poster presentation titled "Examination of Economic Burden Among Commercially Insured Patients with Central Precocious Puberty (CPP)."

Risk scoring tool to predict respiratory syncytial virus hospitalisation in premature infants.

BACKGROUND: The objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate-late preterm infants (32-35 weeks' gestational age) in the Northern Hemisphere. METHODS: Risk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13 475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100-fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated. RESULTS: The risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second-hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut-off scores for RSVH were ≤19 for low- (1.0%), 20-45 for moderate- (3.3%), and 50-56 (9.5%) for high-risk infants. The high-risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3). CONCLUSIONS: This risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate-late preterm infants.

Burden of Respiratory Syncytial Virus Hospitalizations in Canada.

Objective: To examine the socioeconomic burden of respiratory syncytial virus (RSV) disease for Canadian infants hospitalized for the condition. Data and Methods: The descriptive study used data collected in Alberta, Canada, during 2 consecutive RSV seasons. Infants (<1 year of age) were included if they had not received palivizumab and were hospitalized with a confirmed diagnosis of RSV. Hospitalization resource use and parental time burden, out-of-pocket costs, lost work productivity, and stress and anxiety were assessed. Results: 13.4% of all infants (n = 67) had intensive care unit (ICU) admission, and average ICU stay for these infants was 6.5 days. Families had average out-of-pocket expenses of 736.69 Canadian dollars (CAD $), and the average time both parents spent in hospital was nearly 7 days (164.0 hours). For working parents (n = 43), average absenteeism was 49% and overall work impairment was 77.8%. Parents also exhibited significant parental stress (3.6 on the Parental Stressor Scale: 43.9 state anxiety and 36.9 trait anxiety scores). Conclusions: Results indicate a high burden associated with the hospitalization of an infant due to RSV disease in terms of resource use, time, productivity, costs, and stress, even among a population of infants not considered to be at risk for the condition.

Palivizumab in the prevention of severe respiratory syncytial virus infection in children with congenital heart disease; a novel cost-utility modeling study reflecting evidence-based clinical pathways in Spain.

BACKGROUND: Respiratory syncytial virus (RSV) infection remains one of the major reasons of re-hospitalization among children with congenital heart disease (CHD). This study estimated the cost-effectiveness of palivizumab prophylaxis versus placebo, in Spain, from the societal perspective, using a novel cost-effectiveness model reflecting evidence-based clinical pathways. METHODS: A decision-analytic model, combining a decision tree structure in the first year and a Markov structure in later years, was constructed to evaluate the benefits and costs associated with palivizumab versus no prophylaxis among children with CHD. In the first year of the model, children were at risk of mild (i.e. medically attended, MA-RSV) and severe (hospitalized, RSV-H) RSV infection. The impact of delayed corrective CHD surgery due to RSV infection and the consequence of performed surgery despite severe infection were considered. In later years, patients were at risk of developing asthma and allergic sensitization as sequelae of RSV infection. Input data for the model were derived from the pivotal clinical trial and systematic literature reviews. Indirect costs included parental absence from work and nosocomial infections. In agreement with Spanish guidelines, costs and effects were discounted at 3%. RESULTS: Over a lifetime horizon, palivizumab prophylaxis yielded 0.11 and 0.07 additional quality-adjusted life years (QALYs) and life years (LYs), respectively, at additional costs of € 1,693, resulting in an ICER of € 15,748 per QALY gained and € 24,936 per LY gained. Probabilistic sensitivity analyses demonstrated that the probability of palivizumab prophylaxis being cost-effective at a € 30,000 per QALY threshold was 92.7%. The ICER remained below this threshold for most extreme scenario analyses. CONCLUSIONS: The model demonstrated that palivizumab prophylaxis results in more QALYs than no prophylaxis in children with CHD. Palivizumab prophylaxis was shown to be a cost-effective health care intervention according to the commonly accepted standards of cost-effectiveness in Spain (ICER below the threshold of € 30,000 per QALY).

Comparison of pregnancy rates in users of extended and cyclic combined oral contraceptive (COC) regimens in the United States: a brief report.

OBJECTIVE: To evaluate pregnancy rates with 84/7, 21/7, and 24/4 combined oral contraceptives (COCs). STUDY DESIGN: Data were obtained from the i3Invision Data Mart(TM) retrospective claims database. Subjects were 15 to 40 years; first prescribed COCs between January 1, 2006 and April 1, 2011; and continuously insured for ≥1 year. Eighty four over seven users (84/7) were matched 1:1 to 21/7 and 24/4 users. RESULTS: One-year pregnancy rates were significantly lower with 84/7 than with 21/7 (4.4% vs. 7.3%; p<.0001) and 24/4 (4.4% vs. 6.9%, p<.0001) regimens. CONCLUSION: Preliminary results suggest fewer pregnancies with 84/7 versus 21/7 or 24/4 regimens. IMPLICATIONS: While newer COCs, including 84/7 and 24/4 regimens, potentially improve efficacy and alter bleeding profiles compared to 21/7 regimens, few data on comparative pregnancy rates with these regimens are available. In this retrospective claims analysis, real-world pregnancy rates were lower with 84/7 regimens versus 21/7 and 24/4 regimens.

Comparison of rates of and charges from pregnancy complications in users of extended and cyclic combined oral contraceptive (COC) regimens: a brief report.

OBJECTIVE: To evaluate pregnancy complication rates and related charges in users of 84/7, 21/7 and 24/4 combined oral contraceptives (COCs). STUDY DESIGN: Data were obtained from the i3 InVision Data Mart™ retrospective claims database. Subjects were aged 15-40 years, first prescribed a COC between 1/1/2006 and 4/1/2011 and continuously insured for ≥1 year. 84/7 users were matched 1:1 to 21/7 and 24/4 users. RESULTS: Pregnancy-related complication rates and associated charges were significantly lower with 84/7 vs. 21/7 and 24/4 regimens. CONCLUSION: Preliminary data suggest 84/7 regimens may be associated with fewer pregnancy complications and lower related charges.

Costs of Parkinson's disease in a privately insured population.

BACKGROUND: This is the first analysis to estimate the costs of commercially insured patients with Parkinson's disease (PD) in the USA. Prior analyses of PD have not examined costs in patients aged under 65 years, a majority of whom are in the workforce. OBJECTIVE: Our objective was to estimate direct and indirect costs associated with PD in patients under the age of 65 years who are newly diagnosed or have evidence of advanced PD. METHODS: PD patients were selected from a commercially insured claims database (N > 12,000,000; 1999-2009); workloss data were available for a sub-sample of enrollees. Newly diagnosed patients with evidence of similar disorders were excluded. Patients with evidence of advanced PD disease, including ambulatory assistance device users (PDAAD) and institutionalized (PDINST) patients, as well as newly diagnosed PD patients, were analyzed. Each PD cohort was age-, gender- and region-matched to controls without PD. Direct (i.e. insurer payments to providers) and indirect (i.e. workloss) costs were reported in $US, year 2010 values, and were descriptively compared using Wilcoxon rank sum tests. RESULTS: Patients had excess mean direct PD-related costs of $US4,072 (p < 0.001; N = 781) in the year after diagnosis. The PDAAD cohort (N = 214) had excess direct PD-related costs of $US26,467 (p < 0.001) and the PDINST cohort (N = 156) had excess direct PD-related costs of $US37,410 (p < 0.001) in the year after entering these states. Outpatient care was the most expensive cost source for newly diagnosed patients, while inpatient care was the most expensive for PDAAD and PDINST patients. Excess indirect costs were $US3,311 (p < 0.05; N = 173) in the year after initial diagnosis. CONCLUSIONS: Direct costs for newly diagnosed PD patients exceeded costs for controls without PD, and increased with PD progression. Direct costs were approximately 6-7 times higher in patients with advanced PD than in matched controls. Indirect costs represented 45 % of total excess costs for newly diagnosed PD patients.

Early retirement and income loss in patients with early and advanced Parkinson's disease.

BACKGROUND: The indirect costs of Parkinson's disease (PD) may be larger than direct healthcare costs, and the largest component of indirect costs is income loss related to early retirement. No recent retrospective analysis details PD-related early retirement and income loss in the US. OBJECTIVE: We used an observational, matched cohort to study wages and labour force participation over 4 years and to simulate lifetime income losses conditional on being newly diagnosed with PD (naive) or having evidence of increasing disability. METHODS: Actively employed primary beneficiaries of private insurance policies aged 18-64 years with more than two PD diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 332.x) or one diagnosis and a prescription of an antiparkinsonian drug were selected from a privately insured claims database. Continuous health coverage during analysis periods was required. Naive patients were defined as having no claims history indicative of PD during the year prior to first diagnosis or prescription use. A PD with ambulatory assistance devices (PDAAD) cohort was also followed from the date of first evidence of a wheelchair or walker. Controls without PD were matched on age, sex and region. Survival analysis and Wilcoxon rank sum tests were used to compare rates of early retirement and income loss. A simulation of projected economic loss was conducted for PD cohorts diagnosed at different ages using Bureau of Labor Statistics labour force participation and income data. RESULTS: Naive PD patients (n = 278) and PDAAD patients (n = 28) were on average aged 53 years and had significantly higher rates of co-morbidities at baseline versus controls. Conditional on being employed, there was no statistical difference in earnings. However, the hazard of early retirement associated with PD was 2.08 (p < 0.001) for the naive cohort and 5.01 (p < 0.001) for the PDAAD cohort. From age 40 to 79 years, earnings losses in year 2009 values were $US569 393, $US188 590, $US35 496 and $US2451 for those diagnosed at age 45, 55, 65 and 75 years, respectively. Estimates increased by 9% to 37% when using expected 2018 labour force participation estimates. CONCLUSIONS: The cost of early retirement associated with patients with PD was substantial. Given that the proportion of Americans participating in the labour force in older age groups is expected to increase, PD-related early retirement costs will likely rise.