Benralizumab in Severe Eosinophilic Asthma and Chronic Rhinosinusitis with Nasal Polyps: The Real-World, Multi-Country RANS Observational Study.

Purpose: Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting. Patients and Methods: RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥1-point reduction), SNOT-22 total (≥8.9-point reduction), ACQ-6 (≥0.5-point reduction) or ACT (≥3-point increase) scores, were reported. Results: A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was -1.2 (-1.7, -0.6) for NPS, and -19.8 (-23.6, -15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively. Conclusion: In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.

Clinical and Healthcare Resource Use Outcomes between Dual-plane and Prepectoral Techniques in Implant-based Breast Reconstruction: A Multicenter Retrospective Study.

This multicenter, retrospective study compared clinical outcomes and healthcare resource use in patients who underwent dual-plane (DP) or prepectoral (PP) implant-based breast reconstruction (IBR) after mastectomy in the United States. Methods: Medical records were selected for patients at five sites undergoing immediate one-stage direct-to-implant (first hospitalization) or two-stage IBR (first and second hospitalization) using either DP or PP. Inverse probability of treatment weighting was used to adjust for potential confounders. Complications and healthcare resource use were assessed with logistic regression; pain severity was assessed with ordinary least-squares regression. Results: After inverse probability of treatment weighting, data from 255 patients (DP = 130, PP = 125) and 441 breasts (DP = 226, PP = 215) were analyzed. Mean pain severity scores were lower with PP versus DP immediately after IBR for first (P = 0.0002) and second hospitalizations (P = 0.0145), and before discharge for first (P < 0.0001) and second hospitalizations (P = 0.0002). A greater proportion of PP versus DP patients had a shorter hospital length of stay (≤ 23 hours) for first hospitalization (P = 0.0052); proportions were similar for second hospitalization (P = 0.5499). Intravenous narcotics were prescribed less frequently to PP versus DP patients during first (61.1% versus 69.8%, respectively; P = 0.1486) and second (37.5% versus 55.3%, respectively; P = 0.0172) hospitalizations. Complication rates were low in both groups after first hospitalization discharge (DP: 13.6%, PP: 12.5%, P = 0.7225). Conclusion: This retrospective study suggests that the PP technique in IBR may offer benefits related to clinical outcomes and health resource utilization; however, larger studies, including randomized controlled trials, are needed to confirm.

Prevalence of Vitiligo among Children and Adolescents in the United States.

BACKGROUND: Vitiligo is an autoimmune disorder that causes patchy loss of skin pigmentation. Up to 2.16% of pediatric patients may have vitiligo. This study estimated vitiligo point prevalence in children and adolescents (ages: 4-11 and 12-17 years) in the United States (US). METHODS: An online, population-based survey of a nationally representative sample of individuals based on 2017 US Census Bureau estimates for age, race, Hispanic origin, income, and geographic region was conducted from December 2019 to March 2020. Parent/legal guardian proxies responded on behalf of their children or adolescents to vitiligo screening questions. Proxy-reported vitiligo status was adjudicated by expert dermatologists who reviewed photographs of vitiligo lesions uploaded by proxies using a teledermatology application. Estimated point prevalence (including diagnosed and undiagnosed vitiligo and its subtypes) was calculated for proxy-reported and clinician-adjudicated vitiligo. RESULTS: There were 9,118 eligible proxy responses (5,209 children, mean age 7.7 years; 3,909 adolescents, mean age 14.4 years). The proxy-reported vitiligo prevalence (95% confidence interval) for children and adolescents was 1.52% (1.11-1.93) and 2.16% (1.66-2.65), respectively. The clinician-adjudicated prevalence (sensitivity analysis bounds) was 0.84% (0.83-1.23) and 1.19% (1.18-1.74), respectively. Approximately 69% of children and 65% of adolescents had nonsegmental vitiligo (clinician adjudicated) and up to 50% may be undiagnosed. CONCLUSION: Based on the clinician-adjudicated prevalence estimates, there were more than 591,000 cases of vitiligo in children and adolescents in the US in 2020. More than two-thirds had nonsegmental vitiligo and nearly half may be undiagnosed. Future studies should confirm these findings.

Prevalence of Vitiligo Among Adults in the United States.

IMPORTANCE: Vitiligo can have profound effects on patients and is often associated with other autoimmune comorbid conditions. It is important to understand the current prevalence of vitiligo, including diagnosed, undiagnosed, and subtypes (nonsegmental and segmental). OBJECTIVE: To estimate the point prevalence of vitiligo in the US. DESIGN, SETTING, AND PARTICIPANTS: For this population-based study of adults in the US, a cross-sectional online survey was administered between December 2019 and March 2020 to obtain participant self-reported vitiligo status. A representative sample of the US adult general population, aged 18 to 85 years, was recruited using a stratified proportional, sampling design from general population research panels. Additionally, 3 expert dermatologists adjudicated participants' self-reported vitiligo diagnosis by reviewing photographs uploaded by the participants using a teledermatology app designed and tested specifically for this study. MAIN OUTCOMES AND MEASURES: The main outcomes were the point prevalence estimates of overall vitiligo, as well as diagnosed, undiagnosed, nonsegmental, and segmental vitiligo. RESULTS: Among the 40 888 eligible adult participants, the mean (SD) age was 44.9 (17.4) years, 23 170 (56.7%) were female, 30 428 (74.4%) were White, and 4225 (10.3%) were of Hispanic, Latino, or Spanish origin. Self-reported vitiligo prevalence was 1.38% (95% CI, 1.26%-1.49%), with 0.77% (95% CI, 0.68%-0.85%) for diagnosed and 0.61% (95% CI, 0.54%-0.69%) for undiagnosed. Based on expert dermatologist review of 113 photographs of participants with self-reported vitiligo, clinician-adjudicated vitiligo prevalence (sensitivity bounds) was 0.76% (0.76%-1.11%), with 0.46% (0.46%-0.61%) for diagnosed and 0.29% (0.29%-0.50%) for undiagnosed. Self-reported nonsegmental vitiligo prevalence was 0.77% (95% CI, 0.68%-0.85%), with 0.48% (95% CI, 0.41%-0.55%) for diagnosed and 0.29% (95% CI, 0.23%-0.34%) for undiagnosed. Clinician-adjudicated nonsegmental vitiligo prevalence (sensitivity bounds) was 0.58% (0.57%-0.84%), with 0.37% (0.37%-0.49%) for diagnosed and 0.21% (0.20%-0.36%) for undiagnosed. Self-reported segmental vitiligo prevalence was 0.61% (95% CI, 0.53%-0.69%), with 0.28% (95% CI, 0.23%-0.33%) for diagnosed and 0.33% (95% CI, 0.27%-0.38%) for undiagnosed. Clinician-adjudicated segmental vitiligo prevalence (sensitivity bounds) was 0.18% (0.18%-0.27%), with 0.09% (0.09%-0.12%) for diagnosed and 0.08% (0.08%-0.15%) for undiagnosed. CONCLUSIONS AND RELEVANCE: Results of this survey study demonstrated that the current US population-based prevalence estimate of overall (diagnosed and undiagnosed combined) vitiligo in adults is between 0.76% (1.9 million cases in 2020) and 1.11% (2.8 million cases in 2020). Additionally, this study suggests that approximately 40% of adult vitiligo in the US may be undiagnosed. Future studies should be performed to confirm these findings.

Assessment of rituximab-abbs, a biosimilar, and rituximab outcomes in patients with CLL or NHL: A real-world UK study.

BACKGROUND: Rituximab (chimeric anti-CD20 monoclonal antibody) treatment is approved for chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Rituximab-abbs (first biosimilar approved in 2017) is expected to significantly reduce healthcare economic burden due to lower acquisition costs. This non-interventional, non-comparative study assessed real-world effectiveness and tolerability of rituximab-abbs and rituximab in treatment-naive patients with CLL or NHL. MATERIALS AND METHODS: Via an online physician survey, 46 UK-registered hematologists and oncologists retrospectively reported on randomly selected patients aged ≥18 years with CLL or NHL with rituximab-abbs or rituximab as first-line immunotherapy. Overall, 201 patient charts were examined across 4 cohorts: rituximab-abbs in CLL, rituximab-abbs in NHL, rituximab in CLL, rituximab in NHL. RESULTS: Demographic profiles across cohorts were similar. Most patients (94 %-100 %) received combination therapy (rituximab-abbs or rituximab mainly with chemotherapy). For both treatments, overall response rate (94 %-98 %) and 1-year overall survival (98 %-100 %) were very high for patients with CLL or NHL. Most common serious adverse events were neutropenia, fatigue, anemia and infusion reactions. The majority of patients (54 %-66 %) did not experience a grade ≥3 adverse event. Healthcare resource utilization was similarly high across cohorts, driven by diagnostic testing, oncologist office visits, and day-case hospital admissions; many patients required supportive medical therapies. Mean annual savings of ∼£1000/patient driven by acquisition costs occurred with rituximab-abbs versus rituximab, administration costs were similar. CONCLUSION: Rituximab-abbs and rituximab demonstrated similar effectiveness and tolerability in treating CLL and NHL in routine UK clinical practice and demonstrate the utility of the biosimilar as a cost-saving alternative treatment.

A Large Cross-Sectional Survey Study of the Prevalence of Alopecia Areata in the United States.

PURPOSE: Alopecia areata (AA) is an autoimmune disease characterized by the development of non-scarring alopecia. The prevalence is not well known, and estimates vary considerably with no recent estimates in the United States (US). The objective of this study was to define the current AA point prevalence estimate among the general population in the US overall and by severity. PATIENTS AND METHODS: We administered an online, cross-sectional survey to a representative sample of the US population. Participants self-screening as positive for AA using the Alopecia Assessment Tool (ALTO) also completed the Severity of Alopecia Tool (SALT) to measure the severity of disease as a percent of scalp hair loss. Self-reported AA participants were invited to upload photographs for adjudication of AA by 3 clinicians. RESULTS: The average age of participants was 43 years. Approximately half of the participants (49.2%) were male, and the majority were white (77.1%) and not of Hispanic origin (93.2%). Among the 511 self-reported AA participants, 104 (20.4%) uploaded photographs for clinician evaluation. Clinician-adjudicated point prevalence of AA was 0.21% (95% CI: 0.17%, 0.25%) overall, 0.12% (95% CI: 0.09%, 0.15%) for "mild" disease (≤50% SALT score), and 0.09% (95% CI: 0.06%, 0.11%) for "moderate to severe" disease (>50% SALT score) with 0.04% (95% CI: 0.02%, 0.06%) for the alopecia totalis/alopecia universalis (100% SALT score) "moderate to severe" subgroup. The average SALT score was 44.4% overall, 8.8% for "mild", and 93.4% for "moderate to severe". CONCLUSION: This study suggests that the current AA prevalence in the US is similar to the upper estimates from the 1970s at approximately 0.21% (700,000 persons) with the current prevalence of "moderate to severe" disease at approximately 0.09% (300,000 persons). Given this prevalence and the substantial impact of AA on quality of life, the burden of AA within the US is considerable.

A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab.

OBJECTIVES: To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction. METHODS: An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher's exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction. RESULTS: One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p = .0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p < .0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p < .0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p < .0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p < .0001) and total visit time (p = .0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time. LIMITATIONS: Findings may not be representative of care delivery for all RA infusion practices or RA patients. CONCLUSIONS: Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.

Comparison of complication and conversion rates between robotic-assisted and laparoscopic rectal resection for rectal cancer: which patients and providers could benefit most from robotic-assisted surgery?

AIMS: To compare (1) complication and (2) conversion rates to open surgery (OS) from laparoscopic surgery (LS) and robotic-assisted surgery (RA) for rectal cancer patients who underwent rectal resection. (3) To identify patient, physician, and hospital predictors of conversion. MATERIALS AND METHODS: A US-based database study was conducted utilizing the 2012-2014 Premier Healthcare Data, including rectal cancer patients ≥18 with rectal resection. ICD-9-CM diagnosis and procedural codes were utilized to identify surgical approaches, conversions to OS, and surgical complications. Propensity score matching on patient, surgeon, and hospital level characteristics was used to create comparable groups of RA\LS patients (n = 533 per group). Predictors of conversion from LS and RA to OS were identified with stepwise logistic regression in the unmatched sample. RESULTS: Post-match results suggested comparable perioperative complication rates (RA 29% vs LS 29%; p = .7784); whereas conversion rates to OS were 12% for RA vs 29% for LS (p < .0001). Colorectal surgeons (RA 9% vs LS 23%), general surgeons (RA 13% vs LS 35%), and smaller bed-size hospitals (RA 14% vs LS 33%) have reduced conversion rates for RA vs LS (p < .0001). Statistically significant predictors of conversion included LS, non-colorectal surgeon, and smaller bed-size hospitals. LIMITATIONS: Retrospective observational study limitations apply. Analysis of the hospital administrative database was subject to the data captured in the database and the accuracy of coding. Propensity score matching limitations apply. RA and LS groups were balanced with respect to measured patient, surgeon, and hospital characteristics. CONCLUSIONS: Compared to LS, RA offers a higher probability of completing a successful minimally invasive surgery for rectal cancer patients undergoing rectal resection without exacerbating complications. Male, obese, or moderately-to-severely ill patients had higher conversion rates. While colorectal surgeons had lower conversion rates from RA than LS, the reduction was magnified for general surgeons and smaller bed-size hospitals.

Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US.

BACKGROUND: A previous fibromyalgia (FM) research reports that 20%-47% of diagnosed patients may not meet the study definition of FM 1-2 years after diagnosis. The aim of this study was to gain a better understanding of the progression of FM in a geographically diverse cohort over a 2-year time period. METHODS: This cohort study followed 226 subjects recruited online to assess FM and chronic widespread pain (CWP) diagnosis stability over time. At enrollment (baseline), subjects provided informed consent, completed an online questionnaire consisting of the London Fibromyalgia Epidemiology Study Screening Questionnaire to screen for CWP (bilateral pain above/below waist lasting ≥1 week in the past 3 months), visited a site for physician evaluation for FM, and completed a questionnaire with validated patient-reported outcome instruments. Subjects were classified into mutually exclusive groups: FM+CWP+ (screened positive for CWP and received physician diagnosis of FM), FM-CWP+ (screened positive for CWP but did not receive physician diagnosis of FM), and FM-CWP- (screened negative for CWP). Approximately 2 years later (follow-up), subjects were reassessed at the same study site and completed a questionnaire with the same patient-reported outcomes. RESULTS: Seventy-six FM+CWP+ subjects completed assessments at both time points; 56 (73.7%) met the FM study definition at follow-up. Twenty subjects no longer met the FM study definition (eleven became FM-CWP- and nine became FM-CWP+). Ten subjects (two from FM-CWP- and eight from FM-CWP+) transitioned into the FM+CWP+ group at follow-up; they reported more tender points and pain interference with sleep and worse physical function at baseline compared with subjects who did not transition to FM+CWP+. Most (76.7%) of the subjects who transitioned into/out of FM+CWP+ experienced changes in CWP, number of positive tender points, or both. CONCLUSION: The results suggest that some FM+CWP+ patients experience fluctuation in symptoms over time, which may reflect the waxing and waning nature of FM and affect diagnosis and treatment.

Fibromyalgia Outcomes Over Time: Results from a Prospective Observational Study in the United States.

BACKGROUND: Longitudinal research on outcomes of patients with fibromyalgia is limited. OBJECTIVE: To assess clinician and patient-reported outcomes over time among fibromyalgia patients. METHODS: At enrollment (Baseline) and follow-up (approximately 2 years later), consented patients were screened for chronic widespread pain (CWP), attended a physician site visit to determine fibromyalgia status, and completed an online questionnaire assessing pain, sleep, function, health status, productivity, medications, and healthcare resource use. RESULTS: Seventy-six fibromyalgia patients participated at both time points (at Baseline: 86.8% white, 89.5% female, mean age 50.9 years, and mean duration of fibromyalgia 4.1 years). Mean number of tender points at each physician visit was 14.1 and 13.5, respectively; 11 patients no longer screened positive for CWP at follow-up. A majority reported medication use for pain (59.2% at Baseline, 62.0% at Follow-up). The most common medication classes were opioids (32.4%), SSRIs (16.9%), and tramadol (14.1%) at Follow-up. Significant mean changes over time were observed for fibromyalgia symptoms (modified American College of Rheumatology 2010 criteria: 18.4 to 16.9; P=0.004), pain interference with function (Brief Pain Inventory-Short Form: 5.9 to 5.3; P=0.013), and sleep (Medical Outcomes Study-Sleep Scale: 58.3 to 52.7; P=0.004). Patients achieving ≥2 point improvement in pain (14.5%) experienced greater changes in pain interference with function (6.8 to 3.4; P=0.001) and sleep (62.4 to 51.0; P=0.061). CONCLUSION: Fibromyalgia patients reported high levels of burden at both time points, with few significant changes observed over time. Outcomes were variable among patients over time and were better among those with greater pain improvement.

The Comparative Burden of Chronic Widespread Pain and Fibromyalgia in the United States.

BACKGROUND/PURPOSE: Little information exists on the comparative patient and economic burden of chronic widespread pain (CWP) and fibromyalgia (FM) in the United States. METHODS: This multistage, observational study included an online screening survey of a large geographically diverse US sample to assess CWP status, a physician/site visit to determine FM diagnosis, and an online subject questionnaire to capture clinical characteristics, pain, health status, functioning, sleep, healthcare resource use (HRU), productivity, and costs. Based on the screener and physician evaluation, mutually exclusive groups of subjects without CWP (CWP-), with CWP but without FM (CWP+), and with confirmed FM were identified. RESULTS: Disease burden was examined in 472 subjects (125 CWP-, 176 CWP+, 171 FM). Age, race, and ethnicity were similar across groups. Mean body mass index and number of comorbidities increased from CWP- to CWP+ to FM (P = 0.0044, P < 0.0001, respectively). From CWP- to CWP+ to FM, there were reductions in health status (EQ-5D, SF-12) and sleep outcomes (MOS-SS, SSQ) (all P < 0.05). Pain severity, interference with function (BPI-SF), and overall work impairment (WPAI:SHP) increased from CWP- to CWP+ to FM (all P < 0.0001). Higher proportions of CWP+ (52.8%) and FM subjects (62.6%) were taking pain-related prescription medications relative to CWP- subjects (32.8%; P < 0.0001). Significant differences in total direct and indirect costs across the three groups (both P < 0.0001) were observed, with highest costs among FM subjects. CONCLUSION: Fibromyalgia subjects were characterized by the greatest disease burden with more comorbidities and pain-related medications, poorer health status, function, sleep, lower productivity, and higher costs.

Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study.

BACKGROUND: As with many chronic conditions, patients with neuropathic pain (NeP) are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults. METHODS: Subjects (n=624) with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates) were estimated, and differences across pain severity groups were evaluated. RESULTS: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male), and 504/624 (80.8%) reported moderate or severe pain. Statistically significant differences were observed across pain severity levels for number of comorbidities, prescription medications, physician office visits, and lost productivity (all P≤0.0001). At all pain severity levels, indirect costs were the primary cost driver. After adjusting for demographic and clinical variables, total mean (95% confidence interval [CI]) annualized direct medical costs to payers, direct costs to subjects, and indirect costs per subject were US$6,016 (95% CI 5,316-6,716), US$2,219 (95% CI 1,919-2,519), and US$19,000 (95% CI 17,197-20,802), respectively, with significant differences across pain severity levels. CONCLUSION: Subjects with NeP, mainly those showing moderate or severe pain, had significant associations between pain severity and NeP-related health care resource utilization, productivity, and costs. The economic burden, particularly indirect costs, was highest among those with severe pain and higher than previously reported in studies of specific NeP conditions.

Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation.

OBJECTIVE: The aim of this study was to evaluate patient-reported burden associated with peripheral and central neuropathic pain (NeP) by pain severity and NeP condition. DESIGN: Six hundred twenty-four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one-time questionnaire (including EuroQol-5 dimensions, 12-item Short-Form Health Survey, Brief Pain Inventory-Short Form, Medical Outcomes Study Sleep Scale, Hospital Anxiety and Depression Scale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using Kruskal-Wallis (continuous variables) and chi-square or Fisher's exact test (categorical variables). Effect size was computed with Cohen's d (mild vs severe). RESULTS: Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient-reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P < 0.0001). Severe pain subjects were negatively impacted by ≥30% in each outcome compared with mild pain subjects; standardized effect size was moderate for anxiety (0.59) and large (>0.95) for all others. The observed burden was most substantial among chronic low back pain-NeP, although the pattern of disease burden was similar across the six NeP conditions. CONCLUSIONS: Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP, particularly among subjects with severe pain.

Health status, function, productivity, and costs among individuals with idiopathic painful peripheral neuropathy with small fiber involvement in the United States: results from a retrospective chart review and cross-sectional survey.

OBJECTIVE: To characterize the burden of idiopathic painful peripheral neuropathy with small fiber involvement (idiopathic SFN) by pain severity in the US. METHODS: One hundred previously diagnosed idiopathic SFN subjects were enrolled during routine office visits. Subjects completed a one-time questionnaire, and investigators reported clinical characteristics and healthcare resource use, based on 6 month retrospective chart review. Annualized direct and indirect costs were estimated. Results were stratified across pain severity groups. RESULTS: Mean age was 63.5 years; 53.0% were female; 76.0% had moderate or severe pain. Most common comorbidities were sleep disturbance/insomnia (37.0%), anxiety (34.0%), and depressive symptoms (33.0%). Overall mean health status (0.59; -0.11-1.00 scale), physical and mental health (31.7 and 45.6, respectively, 0-100 scale), sleep index (45.1; 0-100 scale), and pain interference with function (5.0; 0-10 scale) differed by pain severity, with worse outcomes among those with greater pain (all p < 0.002). 84.0% were prescribed ≥1 SFN medication. 16.0% were employed; mean overall work impairment was 36.9%. Annualized average adjusted direct and indirect costs per subject ($8055 and $13,733, respectively) differed by pain severity. CONCLUSIONS: Idiopathic SFN subjects with pain experience moderate or severe pain, which negatively impacts health status, function, and productivity, and leads to substantial direct and indirect costs.

Economic and humanistic burden of post-trauma and post-surgical neuropathic pain among adults in the United States.

BACKGROUND: Neuropathic pain (NeP) can be chronic, debilitating, and can interfere with sleep, functioning, and emotional well being. While there are multiple causes of NeP, few studies have examined the disease burden and treatment patterns associated with post-traumatic/post-surgical (PTPS) NeP. OBJECTIVE: To characterize pain, health status, function, health care resource utilization, lost productivity, and costs among subjects with PTPS NeP in the United States. METHODS: This observational study enrolled 100 PTPS NeP subjects recruited during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire with validated measures of pain severity and pain interference, health status, sleep, anxiety and depression, productivity, and study-specific items on demographics, employment status, and out-of-pocket expenses. Investigators completed a case report form based on a 6-month retrospective chart review, recording subjects' clinical characteristics as well as current and previous medications/treatments for NeP. Subjects were stratified into mild, moderate, and severe pain groups. RESULTS: Subjects' demographic characteristics were: mean age of 54.9 years, 53% female, and 22% employed for pay. Mean pain severity score was 5.6 (0-10 scale), with 48% and 35% classified as having moderate and severe pain, respectively. The mean number of comorbidities increased with greater pain severity (P = 0.0009). Patient-reported outcomes were worse among PTPS NeP subjects with more severe pain, including pain interference with function, health state utility, sleep, and depression (P < 0.0001). Eighty-two percent of subjects were prescribed two or more NeP medications. The total mean annualized adjusted direct and indirect costs per subject were $11,846 and $29,617, respectively. Across pain severity levels, differences in annualized adjusted direct and indirect costs were significant (P < 0.0001). CONCLUSION: PTPS NeP subjects reported high pain scores, which were associated with poor health utility, sleep, mood, and function, as well as high health care resource utilization and costs. The quality of life impact and costs attributable to PTPS NeP suggest an unmet need for effective and comprehensive management.

Exact, distribution free confidence intervals for late effects in censored matched pairs.

When comparing censored survival times for matched treated and control subjects, a late effect on survival is one that does not begin to appear until some time has passed. In a study of provider specialty in the treatment of ovarian cancer, a late divergence in the Kaplan-Meier survival curves hinted at superior survival among patients of gynecological oncologists, who employ chemotherapy less intensively, when compared to patients of medical oncologists, who employ chemotherapy more intensively; we ask whether this late divergence should be taken seriously. Specifically, we develop exact, permutation tests, and exact confidence intervals formed by inverting the tests, for late effects in matched pairs subject to random but heterogeneous censoring. Unlike other exact confidence intervals with censored data, the proposed intervals do not require knowledge of censoring times for patients who die. Exact distributions are consequences of two results about signs, signed ranks, and their conditional independence properties. One test, the late effects sign test, has the binomial distribution; the other, the late effects signed rank test, uses nonstandard ranks but nonetheless has the same exact distribution as Wilcoxon's signed rank test. A simulation shows that the late effects signed rank test has substantially more power to detect late effects than do conventional tests. The confidence statement provides information about both the timing and magnitude of late effects.

An Algorithm for Optimal Tapered Matching, With Application to Disparities in Survival.

In a tapered matched comparison, one group of individuals, called the focal group, is compared to two or more nonoverlapping matched comparison groups constructed from one population in such a way that successive comparison groups increasingly resemble the focal group. An optimally tapered matching solves two problems simultaneously: it optimally divides the single comparison population into nonoverlapping comparison groups and optimally pairs members of the focal group with members of each comparison group. We show how to use the optimal assignment algorithm in a new way to solve the optimally tapered matching problem, with implementation in R. This issue often arises in studies of groups Defined by race, gender, or other categorizations such that equitable public policy might require an understanding of the mechanisms that produce disparate outcomes, where certain specific mechanisms would be judged illegitimate, necessitating reform. In particular, we use data from Medicare and the SEER Program of the National Cancer Institute as part of an ongoing study of black-white disparities in survival among women with endometrial cancer.