Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19.

BACKGROUND: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. METHODS: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). RESULTS: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. CONCLUSIONS: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit. CLINICAL TRIALS REGISTRATION: NCT04847622.

Patient-reported health-related quality of life from a randomized, placebo-controlled phase 2 trial of zuranolone in adults with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD), a disabling, potentially life-threatening condition, negatively affects health-related quality of life (HRQoL). This secondary analysis aimed to understand the impact of the neuroactive steroid zuranolone on HRQoL using the Short Form-36v2 Health Survey (SF-36v2). METHODS: Adult patients with MDD and 17-item Hamilton Rating Scale for Depression total score ≥22 were randomized 1:1 to receive zuranolone 30 mg or placebo for 2 weeks, with 4 weeks follow-up. SF-36v2 scores were assessed at Day 15 across 8 domains (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and 2 summary scores (Physical and Mental Component), using a mixed-effects model for repeated measures. Correlations between SF-36v2 scores and clinician-reported efficacy endpoints were assessed using Pearson's correlation. RESULTS: Eighty-nine patients were treated with zuranolone 30 mg (n = 45) or placebo (n = 44). In zuranolone-treated patients, HRQoL improved across all SF-36v2 domains and summary scores at Day 15. Improvements exceeding established minimally important difference thresholds were observed in Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health scores. Improvements in General Health, Vitality, Mental Health, and Mental Component Summary were statistically significant versus placebo (p ≤ 0.025). Clinician-rated endpoints negatively correlated with SF-36v2 scores. LIMITATIONS: The small unipolar depression sample may not be representative of all US MDD patients. HRQoL measures could be impacted by factors unrelated to depression. CONCLUSIONS: Zuranolone-treated patients reported rapid and significant improvements in HRQoL versus placebo at Day 15. HRQoL improvements correlated with improvements in clinician-rated assessments. TRIAL REGISTRATION: clinicaltrials.gov:NCT03000530; https://clinicaltrials.gov/ct2/show/NCT03000530.

Clinical Management of Hospitalized Coronavirus Disease 2019 Patients in the United States.

BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.

Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort.

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO. RESULTS: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Providing community intravenous therapy during the COVID-19 pandemic.

Community intravenous therapy is well-established in most regions of the UK. Although there are national good practice recommendations detailing the service provision of outpatient parenteral antibiotic therapy (OPAT), examples of extended service delivery of other therapies are limited. This article describes the development of a community IV therapy service through integration with acute and primary care teams. IV therapies delivered in addition to antimicrobials safely outside of the hospital setting are also discussed with scope for future areas of development explored. The benefits of care closer to home for patients during the global COVID-19 pandemic are examined, as well as the potential for widening the whole gamut of practice for already established NHS community services through the development of integrated working in a local care organisation.

Achieving clinical response in postpartum depression leads to improvement in health-related quality of life.

OBJECTIVE: To evaluate the health-related quality of life (HRQoL) burden associated with postpartum depression (PPD), determine the extent to which clinical response impacts HRQoL, and estimate the impact of PPD and clinical response on healthcare resource utilization (HRU) and productivity. METHODS: Patient data (n = 127) from two multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating the safety and efficacy of brexanolone injection in adults with PPD were employed for these posthoc analyses. HRQoL and health utility was assessed with the SF-36-v2 Health Survey (SF-36v2) acute version. The 17-item Hamilton Rating Scale for Depression (HAMD-17) total score was used to identify clinical response (≥50% reduction in HAMD-17 total score). Baseline HRQoL burden was assessed by comparison to age- and gender-adjusted population normative data from the 2009 QualityMetric PRO Norming study. The impact of clinical response was evaluated by comparing day 7 and day 30 SF-36v2 scores between clinical responders and non-responders. Interpretations of the meaningfulness of clinical response were indirectly estimated via 2017 National Health and Wellness Survey data linking SF-36v2 mental component summary (MCS) scores to (HRU) and productivity. RESULTS: Baseline HRQoL of patients with PPD was significantly below normative values. Day 7 and day 30 clinical response were associated with large and statistically significant improvements in HRQoL, greater likelihood of meeting SF-36v2 responder definitions, and reduced impairment. MCS levels corresponding to those observed in clinical responders were linked to lower HRU and productivity loss relative to non-responders. CONCLUSIONS: PPD places a substantial burden on HRQoL. Achievement of rapid clinical response (at day 7) and clinical response sustained several weeks following the end of treatment (day 30) led to significant improvement in HRQoL, suggesting the importance of identifying women with PPD and providing effective treatment options.

Number Needed to Treat and Number Needed to Harm analysis of the zuranolone phase 2 clinical trial results in major depressive disorder.

BACKGROUND: Zuranolone (SAGE-217) is a novel, investigational positive allosteric modulator of GABAA receptors being investigated in major depressive disorder (MDD). This analysis of phase 2 data quantified the benefit and risk of zuranolone (30mg) versus placebo and antidepressants in terms of number needed to treat (NNT) and number needed to harm (NNH). METHODS: Rates of response, remission, and all-cause discontinuation for zuranolone and 11 antidepressant comparators were obtained from the zuranolone phase 2 clinical study (N=89) and a published network meta-analysis, respectively. An indirect treatment comparison was conducted using the Bucher method to compare zuranolone to standard-of-care. RESULTS: Zuranolone demonstrated greater benefit compared to placebo on Day 3 (NNT range for response=4-5, NNT for remission=10) and at Day 15 (NNT=3 for response and remission). Compared to SSRIs and SNRIs, zuranolone at Day 15 showed improved treatment response (NNT=4 [95% CI = 3; 16] and 5 [95% CI = 3; 25], respectively) and remission (NNT=4 [95% CI = 2; 13] and 4 [95% CI = 2; 18], respectively). This was accompanied by a reduction in all-cause discontinuation, with negative NNH values (-57 and -28), respectively. LIMITATIONS: Variations in study design across the included trials may limit the generalizability of results. CONCLUSIONS: With a small positive NNT as early as Day 3 indicating robust benefit and a negative NNH indicating reduced harm, this analysis based on a phase 2 study suggests that patients with MDD may benefit from the benefit-to-risk profile of zuranolone.

What Is the Health and Well-Being Burden for Parents Living With a Child With ADHD in the United Kingdom?

Objective: To explore the burden associated with childhood ADHD in a large observational study. Methods: We recruited familes with at least one child (6-18 years) with ADHD via 15 NHS trusts in the UK, and collected data from all family members. We made careful adjustments to ensure a like-for-like comparison with two different control groups, and explored the impact of controlling for a positive parental/carer ADHD screen, employment, and relationship status. Results: We found significant negative impacts of childhood ADHD on parents'/carers' hours and quality of sleep, satisfaction with leisure time, and health-related quality of life (measured by the EuroQol-5D [EQ-5D]). We found a decrement in life satisfaction, mental well-being (as measured by the Short-Warwick Edinburgh Mental Well-Being Scale [S-WEMWBS]), and satisfaction with intimate relationships, but this was not always robust across the different control groups. We did not find any decrement in satisfaction with health, self-reported health status, or satisfaction with income. Conclusion: The study quantifies the impact on the health and well-being of parents living with a child with ADHD using a survey of families attending ADHD clinics in the United Kingdom.

Brexanolone in Postpartum Depression: Post Hoc Analyses to Help Inform Clinical Decision-Making.

Background: Brexanolone (BRX) injection was approved by the United States Food and Drug Administration in 2019 for the treatment of adults with postpartum depression (PPD) based on two Phase 3 clinical trials. Materials and Methods: Data from the three trials were combined. PPD-specific 17-item Hamilton Rating Scale for Depression (HAMD-17) group-level minimal important difference (MID) and patient-level meaningful change (meaningful change threshold [MCT]) were estimated and applied to differences in BRX versus placebo (PBO) at hour 60 (primary endpoint) and day 30 (end of trial follow-up). Likelihood of HAMD-17 response and remission and Clinical Global Impression of Improvement (CGI-I) response for BRX versus PBO were assessed at hour 60 and as sustained through day 30 using relative risk. Associated number needed to treat (NNT) and number needed to harm (NNH) values were also estimated. Results: Two-hundred nine patients were included. The average HAMD-17 MID estimate was -2.1; the least-squared mean difference between BRX and PBO exceeded this at hour 60 and day 30. Minimal, moderate, and large MCTs were estimated to be -9, -15, and -20 points, respectively. Significantly more BRX-treated than PBO-treated patients achieved minimal, moderate, and large change (all ps < 0.05) at hour 60 and large meaningful response at day 30 (p < 0.05). BRX-treated patients were more likely to sustain HAMD-17 remission and CGI-I response through day 30 versus PBO. NNTs ranged from 4 to 8, with NNH of 97. Conclusions: BRX provided meaningful changes relative to PBO, rapid (hour 60), and sustained improvements (day 30) in PPD symptoms, low NNT, and large NNH. These results may help inform treatment decision-making. Clinicaltrials.gov registration numbers: NCT02614547, NCT02942004, and NCT02942017.

Associations between commonly used patient-reported outcome tools in postpartum depression clinical practice and the Hamilton Rating Scale for Depression.

The objective of this study is to explore the associations between the patient-reported Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ)-9 and clinician-reported 17-item Hamilton Depression Rating Scale (HAMD-17) in order to facilitate clinical decision-making. An integrated efficacy dataset of three randomized placebo-controlled trials (NCT02614547, NCT02942004, and NCT02942017) evaluating brexanolone injection, a neuroactive steroid chemically identical to allopregnanolone, in women with postpartum depression was used for this post hoc analysis. Data were pooled across treatment arms. Associations were assessed at day 30 (end-of-trial follow-up). Pearson correlation assessed the relationship between EPDS and PHQ-9 item and total scores and HAMD-17 total score. Cohen's kappa assessed agreement of EPDS remission (score < 10) and PHQ-9 remission (score < 5) with HAMD-17 remission (score ≤ 7). Ordinary least squares (OLS) regression models were used to develop equations estimating HAMD-17 total scores from EPDS and PHQ-9 scores, respectively. The total scores showed large correlations (HAMD-17/EPDS: r = 0.71, p < 0.001; HAMD-17/PHQ-9: r = 0.75, p < 0.001). Individual EPDS and PHQ-9 items significantly correlated (r= 0.35 to 0.67, all p < 0.001) with HAMD-17 total score. EPDS had 79% sensitivity and 67% specificity to detect HAMD-17 remission; corresponding estimates for PHQ-9 were 76% and 78%. OLS models yielded the following equations: HAMD-17 total = 2.66 + (EPDS total × 0.87) and HAMD-17 total = 3.99 + (PHQ-9 total × 0.97). There were large and statistically significant associations between patient-reported outcomes (EPDS, PHQ-9) and clinician-reported outcomes (HAMD-17) as clinical improvements were associated with patient-reported symptom improvement. These results provide tools to help translate clinical trial data to clinical practice, thus aiding shared decision-making for this critical population.

The Cystic Fibrosis Impact Questionnaire: qualitative development and cognitive evaluation of a new patient-reported outcome instrument to assess the life impacts of cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) experience significant disease burden, including progressive pulmonary decline and reduced survival. This multicenter qualitative study was conducted to develop a new patient-reported outcome (PRO) measure to assess the impact of CF on patients' quality of life: the Cystic Fibrosis Impact Questionnaire (CF-IQ). Semi-structured qualitative concept elicitation (CE) interviews with patients and caregivers documented CF-related symptoms, impacts, and treatment experiences. Coded interview data were considered alongside existing PROs, published literature, and expert opinion to develop an initial scale. Three rounds of cognitive interviews evaluated respondent comprehension and facilitated refinement of the CF-IQ. RESULTS: Adult (N = 20) and pediatric (N = 22) patients with CF and their parents/caregivers (N = 22) completed CE interviews at 7 US clinics. The sample included patients aged 6-58 years, 57% females, and represented a broad range of disease severity (forced expiratory volume in 1 s range: 22%-127% predicted). Interviews identified 59 unique CF-related impact concepts in domains, including activity limitations (physical, social, leisure), functional limitations (school, work), vulnerability/lack of control, emotional impact, treatment burden, and future outlook. Concept saturation was achieved, and a draft questionnaire was developed. Findings from the cognitive interviews (n = 18) confirmed that instructions, items, and response scales were relevant and clear, and interpreted as intended by patients. CONCLUSION: The CF-IQ is a 40-item novel PRO scale assessing a comprehensive set of patient-relevant concepts to characterize the multifaceted nature of CF. Qualitative interview data support the content validity of the CF-IQ, which is currently undergoing additional psychometric evaluation in patients with CF.

Cost-Effectiveness of Brexanolone Versus Selective Serotonin Reuptake Inhibitors for the Treatment of Postpartum Depression in the United States.

BACKGROUND: Brexanolone injection (BRX) was approved by the FDA in 2019 for the treatment of adult patients with postpartum depression (PPD), but its cost-effectiveness has not yet been evaluated. OBJECTIVE: To estimate the cost-effectiveness of BRX compared with treatment with selective serotonin reuptake inhibitors (SSRIs) for PPD. METHODS: We projected costs (2018 U.S. dollars) and health (quality-adjusted life-years [QALYs]) for mothers treated with BRX or SSRIs and their children. A health state transition model projected clinical and economic outcomes for mothers based on the Edinburgh Postnatal Depression Scale, from a U.S. payer perspective. The modeled population consisted of adult patients with moderate to severe PPD, similar to BRX clinical trial patients. Short-term efficacy for BRX and SSRIs came from an indirect treatment comparison. Long-term efficacy outcomes over 4 weeks, 11 years (base case), and 18 years were based on results from an 18-year longitudinal study. Maternal health utility values came from analysis of trial-based short-form 6D responses. Other inputs were derived from the literature. RESULTS: The incremental cost-effectiveness ratio for BRX versus SSRIs was $106,662 per QALY gained over an 11-year time horizon. Drug and administration costs for BRX averaged $38,501, compared with $25 for SSRIs over the studied time horizon. Maternal total direct medical costs averaged $65,908 in the BRX arm, compared with $73,653 in the SSRI arm. BRX-treated women averaged 6.230 QALYs compared with 5.979 QALYs for the SSRI arm. Adding partner costs and utilities in a sensitivity analysis further favored BRX. Results were sensitive to the severity of PPD at baseline and the model time horizon. Probabilistic sensitivity analyses indicated that BRX was cost-effective at the $150,000-per-QALY threshold with 58% probability. CONCLUSIONS: Analysis using a state transition model showed BRX to be a cost-effective therapy compared with SSRIs for treating women with PPD. DISCLOSURES: This study was funded by Sage Therapeutics, Cambridge, MA. Eldar-Lissai, Gerbasi, and Hodgkins are employees of Sage Therapeutics and own stock or stock options in the company. Gerbasi also reports previous employment with Policy Analysis Inc. Cohen contributed to this work as an independent consultant. Meltzer-Brody has a sponsored clinical research agreement with Sage Therapeutics to the University of North Carolina, as well as a sponsored research agreement from Janssen to the University of North Carolina, unrelated to this work. Meltzer-Brody has also received personal consulting fees from Cala Health and MedScape, unrelated to this work. Johnson, Chertavian, and Bond are employees of Medicus Economics, which was paid fees by Sage to conduct the research for this study. Study findings do not necessarily represent the views of CEVR or Tufts Medical Center.

Long-Term Outcomes of ADHD: Academic Achievement and Performance.

Objective: The aim of this study was to synthesize published data regarding long-term effects of ADHD on information learned (measured via achievement tests) and success within the school environment (academic performance). Method: A systematic search identified 176 studies (1980-2012) of long-term (≥2 years) academic outcomes with ADHD. Results: Achievement test outcomes (79%) and academic performance outcomes (75%) were worse in individuals with untreated ADHD compared with non-ADHD controls, also when IQ difference was controlled (72% and 81%, respectively). Improvement in both outcome groups was associated with treatment, more often for achievement test scores (79%) than academic performance (42%), also when IQ was controlled (100% and 57%, respectively). More achievement test and academic performance outcomes improved with multimodal (100% and 67%, respectively) than pharmacological (75% and 33%) or non-pharmacological (75% and 50%) treatment alone. Conclusion: ADHD adversely affects long-term academic outcomes. A greater proportion of achievement test outcomes improved with treatment compared with academic performance. Both improved most consistently with multimodal treatment.

Using Matching-Adjusted Indirect Comparisons and Network Meta-analyses to Compare Efficacy of Brexanolone Injection with Selective Serotonin Reuptake Inhibitors for Treating Postpartum Depression.

BACKGROUND: Brexanolone injection, the first therapy approved by the US FDA for the treatment of postpartum depression (PPD) in adults, has been shown to produce a significantly greater decrease in the Hamilton Rating Scale for Depression (HAM-D) total score than placebo in randomised controlled trials (RCTs) of women with PPD. OBJECTIVES: Given the rapid effect of brexanolone injection (within 60 h) sustained throughout the length of the trials (30 days), we sought to compare its efficacy data against selective serotonin reuptake inhibitors (SSRIs), the class of antidepressants most commonly prescribed for PPD, using HAM-D and Edinburgh Postnatal Depression Scale (EPDS) outcomes from currently available RCTs. METHODS: We extracted data from 26 studies identified in a systematic literature review of pharmacological and pharmacological/nonpharmacological combination therapies in PPD. Six studies were suitable to form evidence networks through which to perform indirect treatment comparisons (ITCs) of HAM-D and EPDS outcomes between brexanolone and SSRIs. Having assessed the comparability and suitability of the available evidence for analysis, we discovered significant heterogeneity in the study designs, most notably in the placebo arms of the trials. We therefore conducted matching-adjusted indirect comparisons (MAICs) between brexanolone and the placebo arms of comparator studies, subsequently using the MAIC results of brexanolone versus placebo, and results for SSRIs versus placebo, to form ITCs of brexanolone versus SSRIs at three separate time points-day 3, week 4 and last observation. ITCs were calculated as the differences in change from baseline (CFB) in HAM-D and, separately, CFB in EPDS, between treatments, and reported with 95% confidence intervals (CIs). RESULTS: For all time points, MAICs showed larger differences in CFB for brexanolone compared with SSRIs. Differences (95% CIs) between brexanolone and SSRIs were 12.79 (8.04-17.53) [day 3], 5.87 (- 1.62 to 13.37) [week 4] and 0.97 (- 6.35 to 8.30) [last observation] for the HAM-D. For the EPDS, the differences in CFB were 7.98 (5.32-10.64) [day 3], 6.35 (3.13-9.57) [week 4] and 4.05 (0.79-7.31) [last observation]. Other analytical approaches are also presented to demonstrate the similarity of results, using a network meta-analysis approach, and the importance of using the MAIC method to control for the important heterogeneity between placebo arms. CONCLUSIONS: Acknowledging the limitations of ITCs and this evidence base, when compared with SSRIs, these analyses suggest that brexanolone demonstrated larger differences in CFB for both patient- and clinician-reported PPD outcomes and at all investigated time points after adjusting for differences between placebos in the included studies.

The burden of cystic fibrosis in the Medicaid population.

PURPOSE: To conduct an analysis describing clinical characteristics, pulmonary exacerbation (PEx) events, and health care resource utilization among Medicaid-insured patients with cystic fibrosis (CF). PATIENTS AND METHODS: A retrospective analysis of the Truven Health MarketScan® Medicaid Multi-State administrative claims database (2010-2014) was undertaken. Patients aged ≥6 years with a CF diagnosis, continuously enrolled for 12 months, were identified. Demographics, comorbidities, PEx events, and health care resource utilization and costs over a 12-month enrollment period were analyzed for all patients and by age groups. RESULTS: In total, 1196 patients with CF aged ≥6 years were identified from a sample size of approximately 10 million Medicaid patients. Mean (SD) age was 16.1 (8.8) years. A greater proportion of patients were in younger age groups (6-11 years: 35.5%, 12-17 years: 29.1%, 18-26 years: 25.6%, 27-34 years: 6.7%, ≥35 years: 3.2%). Across all age groups, approximately 90% of patients had at least 1 PEx event; 50.7% of those had a PEx event involving treatment with intravenous antibiotics, and 42.8% required hospitalization. PEx recurrence was frequent: 55.7% of all patients experienced ≥3 PEx events during 1 year. Mean (SD) health care expenditures during a PEx event rose with increasing age, ranging from US$44,589 (US$139,024) to US$116,169 (US$387,752). Overall health care resource utilization was high among patients with CF; 47.2% of the population required an inpatient admission, and 26.8% had subsequent hospitalizations totaling 29.1 days per year in hospital. CONCLUSION: High rates of PEx, hospitalizations, and time spent in hospital demonstrate the significant health care burden of CF among Medicaid beneficiaries.

Health-related quality of life in prisoners with attention-deficit hyperactivity disorder and head injury.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) and head injury (including traumatic brain injury (TBI)) manifest in high levels across prison samples and guidance from the National Institute for Health and Care Excellence notes that people with acquired brain injury may have increased prevalence of ADHD. We aimed to examine the association of ADHD with TBI and the impact of the association upon health-related quality of life (HRQoL) and service use among imprisoned adults. METHODS: An observational study was performed in 2011-2013, at Porterfield Prison, Inverness, United Kingdom (UK). The all male sample included 390 adult prison inmates with capacity to consent and no history of moderate or severe intellectual disability. Head injury was measured with a series of self-reported questions, addressing history of hits to the head: frequency, severity, loss of consciousness (LOC), and sequelae. Participants were interviewed using the Diagnostic Interview for ADHD in Adults 2.0. The Health Utilities Index Mark 3 was used to measure health status, and to calculate attribute specific HRQoL and Quality-Adjusted Life Year (QALY) scores. RESULTS: 72% of prisoners sampled reported at least one head injury in their lifetime. Among those, 70% of head injuries occurred before age 16 and 70% experienced LOC. Prisoners with ADHD were nearly twice more likely to have TBI. Prisoners with ADHD-only and ADHD with co-morbid TBI had significantly lower scores in several HRQoL attributes, compared with TBI only or the absence of either condition. Adjusted logistic regression models indicated an average reduction of 0.20 QALYs in inmates with ADHD-only and 0.30 QALY loss in those with ADHD with co-morbid TBI compared with inmates with neither condition. CONCLUSIONS: There is a robust association between ADHD and TBI, and ADHD with co-morbid TBI confers significantly greater impairment in terms of HRQoL. Managing the short and long-term consequences of TBI is essential to improving care for prisoners and to addressing the criminogenic factors related to them.

The economic consequences of attention-deficit hyperactivity disorder in the Scottish prison system.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is highly prevalent amongst prison inmates and the criminal justice system (CJS) likely bears considerable costs for offenders with ADHD. We aimed to examine the relationship between ADHD and health-related quality of life (HRQoL) and quality-adjusted life years (QALY) amongst imprisoned adults; and to estimate the annual expenditure associated with ADHD status in prison. METHODS: An observational study was performed in 2011-2013, at Porterfield Prison, Inverness, United Kingdom (UK). The all male sample included 390 adult prison inmates with capacity to consent and no history of moderate or severe intellectual disability. Participants were interviewed using the Diagnostic Interview for ADHD in Adults 2.0. The Health Utilities Index Mark 3 (HUI3) was used to measure health status, and to calculate attribute specific HRQoL scores and QALY. Health service utilisation was obtained through inspection of medical prison records. Inmates with ADHD were compared with inmates without ADHD. RESULTS: Inmates with ADHD had significantly lower QALYs, with a clinically significant adjusted difference of 0.13. Psychiatric co-morbidity accounted for the variation of ADHD on the HUI3 emotion domain only. Medical costs for inmates with ADHD were significantly higher; and behaviour-related prison costs were similar to prisoners without ADHD, reflecting a low frequency of recorded critical incidents. CONCLUSIONS: ADHD may directly contribute to adverse health and quality of life through cognitive and executive function deficits, and co-morbid disorders. The extrapolation of conservative cost estimates suggests that the financial burden of medical and behavior-related prison care for inmates with ADHD in the UK is approximately £11.7 million annually. The reported cost estimates are conservative as there is great variability in recorded critical incidents in prisons. In turn, for some prison establishments the prison care costs associated with prisoners with ADHD may be considerably greater.

Community intravenous therapy provision.

Many healthcare services that were once only available in acute settings are now common in the community. Intravenous (IV) therapy is increasingly available as a community service. Given the option, most patients would choose to receive their treatment in a community setting, rather than in hospital. This article describes several outpatient parenteral antimicrobial therapy services, including their advantages and disadvantages. It explores the ways one community NHS trust has developed its community IV therapy service over the past ten years and examines issues pertinent to effective service delivery.

Frequency and costs of pulmonary exacerbations in patients with cystic fibrosis in the United States.

BACKGROUND: Information is limited regarding the cost of pulmonary exacerbations (PEx) among patients with cystic fibrosis in the United States. METHODS: To examine PEx costs, medical chart data were linked to insurance claims for patients aged ≥6 years who had commercial coverage from a large US health insurer affiliated with Optum during 2008-2013. A PEx was categorized as an episode requiring newly started (1) oral antibiotics (PEx-O) or (2) intravenous (IV) antibiotics and/or inpatient stay (PEx-IV). RESULTS: Among 241 patients, 88.0% had ≥1 PEx (2.9/year) of any type, and 48.1% had ≥1 PEx-IV. Prior PEx-IV was the strongest risk factor for subsequent PEx-IV. The mean cost per episode was $12,784 for PEx of any type and $36,319 for PEx-IV. Patients with worse lung function were more likely to experience a PEx and incurred higher annual PEx-related costs. LIMITATIONS: This was an observational study using a convenience sample of patients with commercial coverage from a large US health insurer whose medical charts were available for abstraction. Results of the study may not be generalizable to individuals with Medicaid coverage and other types of insurance, or to the uninsured. CONCLUSIONS: Most patients experience ≥1 PEx annually, and nearly half require IV antibiotics and/or inpatient stay at considerable cost.