Establishing US norms for the Adult ADHD Self-Report Scale (ASRS-v1.1) and characterising symptom burden among adults with self-reported ADHD.

AIMS: To estimate Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist normative total scores among the US adult general population and to evaluate overall attention-deficit hyperactivity disorder (ADHD) symptom burden among US adults with ADHD. METHODS: Prior 2012 and 2013 US National Health and Wellness Survey respondents were re-contacted. Demographics, comorbidities, and ASRS-v1.1 data were collected. ASRS-v1.1 scores were compared by sex, age, ADHD diagnosis, and ADHD medication use. Group differences were evaluated using chi-square tests and independent samples t-tests for categorical and continuous variables, respectively. RESULTS: Of 22 397 respondents, 465 self-reported being diagnosed with ADHD by a physician; of these, 174 self-reported using ADHD medication. The mean ASRS-v1.1 total score was 2.0 (SD = 3.2); scores differed by age and sex (all, P < 0.001). ADHD (vs no ADHD) was associated with depression (58.1% vs 18.0%), anxiety (53.1% vs 16.0%), and sleep difficulties (37.0% vs 14.0%) (all, P < 0.001). ADHD medication use (vs no use) was associated with depression (68.4% vs 51.9%), anxiety (67.2% vs 44.7%), panic disorder (25.9% vs 17.2%), and insomnia (27.6% vs 19.6%) (all, P < 0.05). ADHD (vs no ADHD) respondents scored higher on all 18 ASRS-v1.1 items (all, P < 0.05). Medication users (vs non-users) scored higher on six items (all, P < 0.05). DISCUSSION: Adult ADHD may be undertreated or sub-optimally treated, despite a high symptom burden. Normative data will allow comparisons with individuals' scores to support the assessment of ADHD symptom burden among adults. CONCLUSION: Findings highlight the importance of assessing ADHD symptom burden, especially among adults presenting with comorbidities.

Review of the impact of NNRTI-based HIV treatment regimens on patient-reported disease burden.

While the burden of HIV disease is well documented, the value of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy regimens in reducing patient burden is not well understood. The purpose of this study was to examine patient-reported health among those receiving NNRTI-based regimens to understand their incremental value in reducing the burden of HIV. We conducted a structured literature review using PubMed to identify NNRTI trials utilizing validated patient-reported outcome (PRO) instruments during 2005-2011. The search strategy included a PubMed search to identify relevant studies based on disease, instrument, PRO, and NNRTI medication terms; and a manual search of bibliographies of identified papers. Data abstracted from each study included study type, treatment regimen(s), and PRO results. Of 11 trials identified, 8 (73%) reported significance of changes in a PRO over time and 10 (91%) reported significance of PRO changes between groups. Several domains were assessed, with significant findings (between or within groups) observed in: physical health/well-being (n = 5), emotional status/well-being (n = 2), symptoms (n = 2), anxiety (n = 2), gastrointestinal upset (n = 2), psychological health (n = 1), functional and global well-being (n = 1), fatigue/energy (n = 1), depression (n = 1), change in body appearance (n = 1), pain (n = 1), headache (n = 1), bad dreams/nightmares (n = 1), problems having sex (n = 1), and general health perception (n = 1). In conclusion, NNRTIs have been observed most frequently to improve patient-reported physical health and well-being. Treatments are needed that can also reduce patient burden in areas of emotional well-being, cognitive functioning, and overall symptom profile.

Responsiveness of the MOS-HIV and EQ-5D in HIV-infected adults receiving antiretroviral therapies.

BACKGROUND: Selection of an appropriate patient-reported outcome (PRO) instrument for a clinical trial requires knowledge of the instrument's responsiveness to detecting treatment effects. The purpose of this study was to examine the responsiveness of two health-related quality of life (HRQL) instruments used in clinical trials involving HIV-infected adults: the HIV-targeted Medical Outcomes Study HIV Health Survey (MOS-HIV), and a generic measure, the EuroQol-5D (EQ-5D). METHODS: A systematic review identified clinical trials using the MOS-HIV or EQ-5D to assess outcomes for HIV-infected adults. Data abstracted from each study included study type, treatment regimen(s), PRO results, and effect size (either reported or calculated). Effect size was calculated as the difference between baseline and follow-up mean scores divided by the baseline standard deviation. Magnitude was categorized as small (d=0.20), medium (d=0.50), and large (d=0.80). RESULTS: Between 2005 and 2010, the MOS-HIV was administered in 12 trials. Significant differences were observed between groups and over time in physical health summary (PHS) and mental health summary (MHS) scores (P<0.05) in subjects switching therapy after experiencing Grade-2 adverse events. Effect sizes were medium (0.55 and 0.49 for PHS and MHS, respectively) among treatment-naïve adults beginning therapy (two studies), but negligible among treatment-experienced adults (0.04 and 0.13 for PHS and MHS, respectively; three studies). The EQ-5D was used in five trials between 2001 and 2010. It was responsive to occurrences of adverse events and opportunistic infections, with small-to-medium effect sizes (range 0.30-0.50) in each of its five dimensions. CONCLUSIONS: A systematic review of PRO study results showed both the MOS-HIV and EQ-5D were responsive to changes between groups and/or over time in treatment-naïve HIV-infected patients. These instruments may be used either individually or together in clinical trials to measure changes in HRQL.

Patient reported outcome instruments used in clinical trials of HIV-infected adults on NNRTI-based therapy: a 10-year review.

BACKGROUND: Patient-reported outcomes (PROs) may provide valuable information to clinicians and patients when choosing initial antiretroviral therapy. OBJECTIVE: To identify and classify PRO instruments used to measure treatment effects in clinical trials evaluating NNRTIs. METHODS: We conducted a structured literature review using PubMed to identify NNRTI trials published from March 2003 to February 2013. Studies identified--based on disease, instrument, PRO, and NNRTI medication terms were reviewed--to identify PRO instruments. Domains measured within each instrument were recorded to understand key areas of interest in NNRTIs. RESULTS: Of 189 articles reviewed, 27 validated instruments were administered in 26 unique trials, with a mean of 1.9 instruments (median: 1; range: 1-7) per trial. The Medical Outcomes Study HIV Health Survey (MOS-HIV) was the most commonly used instrument (n = 8 trials). Seventeen trials (65%) included at least one multidimensional health-related quality of life (HRQL) instrument (HIV-targeted, n = 11; general, n = 8). Other validated instruments measured sleep (n = 5), depression (n = 5), anxiety (n = 4), psychiatric symptoms (n = 2), beliefs about HIV medications (n = 2), HIV symptoms (n = 1), and stress (n = 1). CONCLUSIONS: Although review of recent NNRTI trials suggests a lack of consensus on the optimal PRO instruments, a typical battery is comprised of a multidimensional HRQL measure coupled with one or more symptom measures. Further work is needed to clarify advantages and disadvantages of using specific PRO instruments to measure relevant constructs and to identify the most useful batteries of instruments for NNRTI trials.

Rising United States Hospital Admissions for Acute Bacterial Skin and Skin Structure Infections: Recent Trends and Economic Impact.

BACKGROUND: The number of ambulatory patients seeking treatment for skin and skin structure infections (SSSI) are increasing. The objective of this study is to determine recent trends in hospital admissions and healthcare resource utilization and identify covariates associated with hospital costs and mortality for hospitalized adult patients with a primary SSSI diagnosis in the United States. METHODS: We performed a retrospective cross-sectional analysis (years 2005-2011) of data from the US Healthcare Cost and Utilization Project National Inpatient Sample. Recent trends, patient characteristics, and healthcare resource utilization for patients hospitalized with a primary SSSI diagnosis were evaluated. Descriptive and bivariate analyses were conducted to assess patient and hospital characteristics. RESULTS: A total of 1.8% of hospital admissions for the years 2005 through 2011 were for adult patients with a SSSI primary diagnosis. SSSI-related hospital admissions significantly changed during the study period (P < .001 for trend) ranging from 1.6% (in 2005) to 2.0% (in 2011). Mean hospital length of stay (LOS) decreased from 5.4 days in the year 2005 to 5.0 days in the year 2011 (overall change, P < .001) with no change in hospital costs. Patients with postoperative wound infections had the longest hospital stays (adjusted mean, 5.81 days; 95% confidence interval (CI), 5.80-5.83) and highest total costs (adjusted mean, $9388; 95% CI, $9366-$9410). Year of hospital admission was strongly associated with mortality; infection type, all patient refined diagnosis related group severity of illness level, and LOS were strongly associated with hospital costs. CONCLUSIONS: Hospital admissions for adult patients in the United States with a SSSI primary diagnosis continue to increase. Decreasing hospital inpatient LOS and mortality rate may be due to improved early treatment. Future research should focus on identifying alternative treatment processes for patients with SSSI that could shift management from inpatient to outpatient treatment settings.

Cost of treatment in a US commercially insured, HIV-1-infected population.

OBJECTIVE: Recent treatment patterns and cost data associated with HIV in the United States are limited. This study assessed first-line persistence and healthcare costs of HIV-1 in patients by treatment line and CD4 cell count. METHODS: MarketScan Commercial Claims and Encounters Database (2007-2011) and Lab Database (2007-2010) were used to construct two HIV-1 cohorts: 1) newly treated HIV-1-infected patients with ≥6 months' continuous enrollment prior to first third-agent drug claim (Newly Treated Cohort) and 2) CD4 cell count test results (CD4 Measurements Cohort). All patients were ≥18 years old and without hepatitis co-infection. The Kaplan-Meier method was used to measure treatment switch rates. Generalized linear models (gamma distribution, log link) were used to compare healthcare costs by treatment line and CD4 cell count controlling for potential confounders. RESULTS: Newly treated patients (n = 8,617) had mean age of 41, 82% were male, and 20% had experienced AIDS-defining events at baseline. Over 20% of newly treated patients switched initial treatment regimen within 2 years. Average unadjusted (and covariate-adjusted) total healthcare cost/year was $33,674 ($28,861) for first-line, $39,191 ($35,805) for second-line, and $39,882 ($40,804) for third-line treatment. Covariate-adjusted costs of care on second- and third-line treatments were significantly more expensive than first-line treatment (24% [p<0.001] and 41% [p = 0.006] higher, respectively). The CD4 Measurements Cohort included 803 CD4 measurements (mean age 49, 76% male, 8% experienced an AIDS-defining event). Costs associated with CD4 measurements <100 cells/µL were 92% higher than those with >350 cells/µL (p<0.001). For higher CD4 cell counts, the majority of expenditures were for antiretrovirals (64% of total for CD4 >350 cells/µL). CONCLUSIONS: Despite modern advances in antiretroviral therapy and medical care, direct medical costs of HIV-1-infected patients increase after treatment switch and with lower CD4 counts, consistent with previous costing studies.

The prevalence of transmitted resistance to first-generation non-nucleoside reverse transcriptase inhibitors and its potential economic impact in HIV-infected patients.

Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) including efavirenz is recommended as a 1(st)-line treatment choice in international HIV guidelines, and it is one of the most common components of initial therapy. Resistance to 1(st)-generation NNRTIs is found among treated and untreated HIV-infected individuals creating a subpopulation of HIV-infected individuals in whom efavirenz is not fully effective. This analysis reviewed published articles and conference abstracts to examine the prevalence of 1(st)-generation NNRTI resistance in Europe, the United States (US), and Canada and to identify published evidence of the economic consequences of resistance. The reported prevalence of NNRTI resistance was generally higher in US/Canada than in Europe and increased in both regions from their introduction in the late 1990s until the early 2000s. The most recent time-based trends suggest that NNRTI-resistance prevalence may be stable or decreasing. These estimates of resistance may be understated as resistance estimates using ultra-sensitive genotypic testing methods, which identify low-frequency mutations undetected by standard testing methods, showed increased prevalence of resistance by more than two-fold. No studies were identified that explicitly investigated the costs of drug resistance. Rather, most studies reported costs of treatment change, failure, or disease progression. Among those studies, annual HIV medical costs of those infected with HIV increased 1) as CD4 cells decreased, driven in part by hospitalization at lower CD4 cell counts; 2) for treatment changes, and 3) for each virologic failure. The possible erosion of efficacy or of therapy choices through resistance transmission or selection, even when present with low frequency, may become a barrier to the use of 1(st)-generation NNRTIs and the increased costs associated with regimen failure and disease progression underlie the importance of identification of treatment resistance to ensure optimal initial therapy choice and regimen succession.