Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings.

BACKGROUND: This analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE). METHODS: The RECOVER (Remission From Chronic Opioid Use: Studying Environmental and Socioeconomic Factors on Recovery) study recruited participants from BUP-XR clinical trials (NCT02357901, NCT025100142, and NCT02896296) to assess whether there were sustained benefits after leaving the trial. Abstinence from opioids and from all illicit substances (excluding medical cannabis), health-related quality of life, depression, and employment were measured after BUP-XR discontinuation and change in outcomes assessed at 6, 12, and 18 months. Results were analyzed within the full cohort and by duration of BUP-XR treatment (0-2 months, 3-5 months, 6-11 months, 12 months, or 13-18 months) with and without inverse probability weights adjusting for differences in baseline characteristics. RESULTS: Of 533 participants, 529 were assessed over the 18-month study period. Further posttrial pharmacotherapy was reported by 33% of participants. At RECOVER baseline, longer BUP-XR was associated with higher abstinence (0-2 months BUP-XR [n = 116]: 38.8%; 3-5 months BUP-XR [n = 61]: 41.0%; 6-11 months BUP-XR [n = 86]: 68.6%; 12 months BUP-XR [n = 135]: 71.9%; 18 months BUP-XR [n = 131]: 88.2%) and greater 12-Item Short Form Health Survey mental component scores. Over 60% of participants had stable or improved outcomes at 6, 12, and 18 months assessments. Overall 47% of participants self-reported sustained opioid abstinence for the full 18-month follow-up, with greater sustained abstinence associated with longer BUP-XR treatment duration. A sensitivity analysis, removing patients receiving medications for OUD, yielded similar results. CONCLUSIONS: Participants from BUP-XR clinical trials who continued into RECOVER maintained or improved on numerous outcomes over 18 months, demonstrating the long-term positive impact of OUD pharmacotherapy.

Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma.

Here, we report the first comparative analysis of patient-reported outcomes (PROs) with chimeric antigen receptor T-cell therapy vs standard-of-care (SOC) therapy in second-line relapsed/refractory large B-cell lymphoma (R/R LBCL) from the pivotal randomized phase 3 ZUMA-7 study of axicabtagene ciloleucel (axi-cel) vs SOC. PRO instruments were administered at baseline, day 50, day 100, day 150, month 9, and every 3 months from randomization until 24 months or an event-free survival event. The quality of life (QoL) analysis set comprised patients with a baseline and ≥1 follow-up PRO completion. Prespecified hypotheses for Quality of Life Questionnaire-Core 30 (QLQ-C30) physical functioning, global health status/QoL, and EQ-5D-5L visual analog scale (VAS) were tested using mixed-effects models with repeated measures. Clinically meaningful changes were defined as 10 points for QLQ-C30 and 7 for EQ-5D-5L VAS. Among 359 patients, 296 (165 axi-cel, 131 SOC) met inclusion criteria for QoL analysis. At day 100, statistically significant and clinically meaningful differences in mean change of scores from baseline were observed favoring axi-cel over SOC for QLQ-C30 global health status/QoL (estimated difference 18.1 [95% confidence interval (CI), 12.3-23.9]), physical functioning (13.1 [95% CI, 8.0-18.2]), and EQ-5D-5L VAS (13.7 [95% CI, 8.5-18.8]; P < .0001 for all). At day 150, scores significantly favored axi-cel vs SOC for global health status/QoL (9.8 [95% CI, 2.6-17.0]; P = .0124) and EQ-5D-5L VAS (11.3 [95% CI, 5.4-17.1]; P = .0004). Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03391466.

A quality-adjusted survival time without symptoms or toxicities analysis of glasdegib plus low-dose cytarabine versus low-dose cytarabine as initial therapy for acute myeloid leukemia in patients who are not considered candidates for intensive chemotherapy.

BACKGROUND: In a randomized study, glasdegib (a hedgehog inhibitor) plus low-dose cytarabine (LDAC) significantly prolonged survival in comparison with LDAC in patients with acute myeloid leukemia (AML). A quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) approach was used to evaluate comparative quality-adjusted survival. METHODS: Overall survival was partitioned into the following: time with any treatment-emergent grade 3 or higher adverse events (TOX); time without symptoms of disease progression or toxicity (TWiST); and time after treatment discontinuation due to insufficient clinical response, relapse, or death time after progression (REL). Q-TWiST was calculated by multiplying the restricted mean time in each state by respective utilities and then summing up the utility-adjusted time. RESULTS: At 20 months of follow-up, the survival probabilities for the glasdegib-LDAC arm and the LDAC arm were 28.2% and 7.9%, respectively. Glasdegib-LDAC patients (n = 78), in comparison with LDAC patients (n = 38), had significantly longer mean TWiST (+3.4 months; 95% confidence interval [CI], 1.8-5.2 months) and TOX (+0.8 months; 95% CI, 0.1-1.6 months) and longer but nonsignificant REL (+0.3 months; 95% CI, -1.9 to 2.3 months). Q-TWiST was 4.0 months (95% CI, 2.1-5.8 months) longer with glasdegib plus LDAC, and this translated into a 75% relative improvement in quality-adjusted survival with respect to LDAC. Results were robust to the length of follow-up (6-24 months) and remained significant when all adverse events, regardless of grade, were included. CONCLUSIONS: These results suggest that most of the survival benefit from glasdegib plus LDAC versus LDAC alone is TWiST, and this represents added time in relatively "good" health. These results support the clinical value of glasdegib plus LDAC as initial therapy for AML in patients for whom intensive chemotherapy is not an option.

Early switch/early discharge opportunities for hospitalized patients with methicillin resistant Staphylococcus aureus complicated skin and soft tissue infections: Saudi Arabia and United Arab Emirates.

OBJECTIVES: To describe opportunities for early switch (ES) from intravenous (IV) to oral (PO) antibiotics and early discharge (ED) of patients hospitalized in the Kingdom of Saudi Arabia (KSA) and the United Arab Emirates (UAE) with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTIs). METHODS: This retrospective medical chart review study enrolled physicians from 16 KSA and UAE sites to collect data for 107 MRSA cSSTI patients. RESULTS: Actual length of MRSA-active treatment was 13.3±9.3 mean days in KSA and 11.2±3.9 mean days in UAE, with a mean of 11.8±9.3 days of MRSA-targeted IV therapy in KSA and 10.7±4.3 days in UAE. 12.5% in KSA met ES criteria and potentially could have discontinued IV therapy 4.0±2.9 days sooner; 44.0% in UAE could have discontinued 6.6±3.6 days sooner. Patients were hospitalized for a mean 28.6±45.0 days in KSA and 13.1±5.9 days in UAE. 25.0% in KSA and 48.0% in UAE met ED criteria and potentially could have been discharged 6.1±8.0 days earlier in KSA and 7.9±5.0 days earlier in UAE. CONCLUSIONS: A significant proportion of patients hospitalized for MRSA cSSTI could be eligible for ES or ED opportunities, resulting in potential for reductions in IV and bed days.

Recovery From Opioid Use Disorder (OUD) After Monthly Long-acting Buprenorphine Treatment: 12-Month Longitudinal Outcomes From RECOVER, an Observational Study.

OBJECTIVES: While evidence has mounted regarding the short-term effectiveness of pharmacotherapy for opioid use disorder (OUD), little is known about longer-term psychosocial, economic, and health outcomes. We report herein 12-month outcomes for an observational study enrolling participants who had previously taken part in a long-acting buprenorphine subcutaneous injection (BUP-XR) trial for moderate to severe OUD. METHODS: The RECOVER (Remission from Chronic Opioid Use: Studying Environmental and SocioEconomic Factors on Recovery; NCT03604861) study enrolled participants from 35 US community-based sites. Self-reported sustained opioid abstinence over 12 months and self-reported past-week abstinence at 3-, 6-, 9-, and 12-month visits were assessed. Multiple regression models assessed the association of BUP-XR duration with abstinence, controlling for potential confounders. Withdrawal, pain, health-related quality of life, depression, and employment at RECOVER baseline and 12-month visits were also compared to values collected before treatment in the BUP-XR trial. RESULTS: Of 533 RECOVER participants, 425 completed the 12-month visit (average age 42 years; 66% male); 50.8% self-reported sustained 12-month and 68.0% past-week opioid abstinence. In multiple regressions, participants receiving 12-month versus ≤2-month BUP-XR treatment duration had significantly higher likelihood of sustained opioid abstinence (75.3% vs 24.1%; P = 0.001), with similar results for past-week self-reported abstinence over time. During RECOVER, participants had fewer withdrawal symptoms, lower pain, positive health-related quality of life, minimal depression, and higher employment versus pre-trial visit. CONCLUSIONS: RECOVER participants reported positive outcomes over the 12-month observational period, including high opioid abstinence and stable or improved humanistic outcomes. These findings provide insights into the long-term impact of pharmacotherapy in OUD recovery.

Effects of monthly buprenorphine extended-release injections on patient-centered outcomes: A long-term study.

INTRODUCTION: The physical, social, psychological, and economic burden of opioid use disorder (OUD) is substantial. As of the year 2019, the predominant focus of OUD research was outcomes such as retention and abstinence. We report herein the effects of extended-release buprenorphine (BUP-XR), the first FDA-approved subcutaneously injected, monthly treatment for OUD, on patient-centered outcomes. MATERIALS AND METHODS: Patient-centered outcomes were collected during an open-label safety study of participants with OUD (NCT# 02510014) evaluating BUP-XR. Measures collected during the study included the EQ-5D-5L, SF-36v2, Treatment Effectiveness Assessment (TEA), Addiction Severity Index-Lite (ASI-Lite), employment/insurance status questionnaire, and Medication Satisfaction Questionnaire (MSQ). Changes from baseline to end of study week 49 were analyzed using mixed models for repeated measures. "Baseline" was defined as the value collected prior to the first BUP-XR injection. Results presented are for those participants who initiated treatment on BUP-XR during the open-label study and were eligible to receive up to 12 injections. RESULTS: Four hundred twelve participants were included in analyses; 206 participants discontinued BUP-XR prematurely. Mean EQ-5D-5L scores remained stable from baseline to end of study. Statistically significant improvements from baseline to end of study were noted for the SF-36v2 mental component summary score (difference = 5.0, 95%CI: 3.5-6.5) and 7 of 8 domain scores (P < .05 for all comparisons); the SF-36v2 physical component summary remained stable from baseline to end of study. The TEA total score (difference = 9.3 points, 95%CI: 8.0-10.5) and 4 of 4 domain scores (difference = 2-3 points per domain) significantly improved from baseline to end of study. Significant improvements (P < .05 for all comparisons) on the ASI-Lite were seen for all problem areas except alcohol use from baseline to end of study. Employment rate increased 7% whereas health insurance status remained stable from baseline to end of study. Medication satisfaction measured using the MSQ was >88% at end of study. CONCLUSIONS: Treatment with BUP-XR monthly injections for up to 12 months in this cohort of treatment-seeking individuals with OUD led to positive PCOs and high treatment satisfaction, which correspond to personal recovery.

A Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) Analysis of Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma (aRCC).

BACKGROUND: This analysis compared quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) between nivolumab and everolimus among previously treated patients with advanced renal cell carcinoma enrolled in the phase III CheckMate 025 trial (NCT01668784). MATERIALS AND METHODS: At 45-month follow-up, overall survival (OS) was partitioned into 3 health states: TWiST, time with grade ≥ 3 toxicity (TOX), and time after progression (REL). Mean Q-TWiST was determined by multiplying each state's duration with its utility (TWiST, 1.0; TOX, 0.5; REL, 0.5). Relative Q-TWiST gains (calculated as Q-TWiST difference divided by everolimus OS) of ≥ 10% were predefined as clinically important. Immuno-oncology-specific sensitivity analyses considered 4 alternative progression definitions: Tumor size increase ≥ 25% from nadir; treatment discontinuation; ≥ 2-point reduction from baseline in Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms scores; and a composite definition. A scenario incorporating grade ≥ 2 toxicities was tested. RESULTS: Compared with everolimus, nivolumab was associated with a significant Q-TWiST improvement of 3.3 months (P < .001). In all sensitivity analyses, nivolumab was associated with Q-TWiST gains (relative gain %) ranging from 3.3 months (14.4%) to 4.8 months (20.9%). CONCLUSIONS: Nivolumab is associated with a statistically significant and clinically meaningful gain in quality-adjusted OS versus everolimus among previously treated patients with advanced renal cell carcinoma.

Patient-reported outcomes in schizophrenia patients treated with once-monthly extended-release risperidone in a long-term clinical study.

PURPOSE: RBP-7000 (PERSERIS™) is a once-monthly subcutaneous extended-release risperidone formulation approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. The objective of this study was to describe the long-term impact of RBP-7000 on health-related quality of life (HRQoL), subjective well-being, treatment satisfaction and medication preference in patients with schizophrenia. PATIENTS AND METHODS: HRQoL was derived from a 52-week multicentre Phase III single-arm open-label outpatient study that assessed the safety and efficacy of RBP-7000 (120 mg) in patients with schizophrenia. HRQoL was measured using the EuroQol EQ-5D-5L and Short-Form Survey SF-36 version 2; well-being using the Subjective Well-being Under Neuroleptic Treatment - Short Version (SWN-S); satisfaction using the Medication Satisfaction Questionnaire and medication preference using the Preference of Medication questionnaire. RESULTS: Of 482 participants at baseline, 234 remained through the end of study (EOS; week 52). Mean HRQoL and well-being scores remained stable between baseline (EQ-5D-5L index: 0.83; SF-36v2 Physical Component Score: 50; SF-36v2 Mental Component Score: 46; total SWN-S score: 89) and EOS (EQ-5D-5L index: 0.86; SF-36v2 Physical Component Score: 49; SF-36v2 Mental Component Score: 47; total SWN-S score: 90). The proportion of participants reporting satisfaction increased between week 4 (66%) and EOS (81%), with a similar trend for the preference of RBP-7000 over previous treatment (week 4: 66%; EOS: 72%). Sensitivity analyses suggested a minor effect of dropout on characterization of change over time in patient-reported outcomes (PRO) measures. CONCLUSION: Study participants attained mean HRQoL scores near that of the general US population. Over two-thirds reported high satisfaction with and preference for RBP-7000 across the study period. Additional research is needed to confirm whether these PRO translate into improved outcomes such as adherence and ultimately fewer relapses in patients with schizophrenia.

Measuring recovery in opioid use disorder: clinical utility and psychometric properties of the Treatment Effectiveness Assessment.

Purpose: The Treatment Effectiveness Assessment (TEA) is a patient-centered instrument for evaluating treatment progress and recovery from substance use disorders, including opioid use disorder (OUD). We assessed the TEA's reliability and validity and determined minimal clinically important differences (MIDs) in participants with moderate to severe OUD. Patients and methods: The TEA measures change in four single-item domains (substance use, health, lifestyle, community involvement) from treatment initiation across the duration of a treatment program. Self-reported responses range from 1 ("none or not much") to 10 ("much better") with items summed to a total score ranging from 4-40. We assessed floor and ceiling effects, internal consistency, test-retest reliability, known-groups validity (ANOVA stratified by current health status [36-Item Short Form Health Survey item 1]), convergent/divergent validity, and MIDs using data from a phase 3, open-label clinical trial of buprenorphine extended-release monthly injection for subcutaneous use (BUP-XR). Participants with OUD completed the TEA at screening and before monthly injections for up to 12 months. Results: Among 410 participants (mean age 38 years; 64% male), the mean baseline (pre-injection 1) TEA total score was 25.4 (SD 9.7), with <10% of participants at the measure floor and 10%-20% at the ceiling across domains. Internal consistency was high (Cronbach's α=0.90), with marginal test-retest reliability (intraclass correlation coefficient =0.69). Mean TEA total score consistently increased from baseline (n=410; mean 25.4 [SD 9.7]) to end of study (n=337; 35.0 [6.7]) and differentiated between current health status groups (P<0.001); it was weakly correlated with other measures of health-related quality of life/severity. MIDs ranged from 5-8 for the TEA total score across anchor- and distribution-based approaches. Conclusion: The TEA exhibited acceptable reliability and validity in a cohort of participants with moderate to severe OUD treated with BUP-XR. Given its brevity and psychometric properties, the TEA is a promising tool for use in clinical practice and research.

Patient-centered Outcomes in Participants of a Buprenorphine Monthly Depot (BUP-XR) Double-blind, Placebo-controlled, Multicenter, Phase 3 Study.

OBJECTIVE: Opioid use disorder (OUD) is associated with physical, social, psychological, and economic burden. This analysis assessed the effects of RBP-6000, referred to as BUP-XR (extended-release buprenorphine), a subcutaneously injected, monthly buprenorphine treatment for OUD compared with placebo on patient-centered outcomes measuring meaningful life changes. METHODS: Patient-centered outcomes were collected in a 24-week, phase 3, placebo-controlled study assessing the efficacy, safety, and tolerability of BUP-XR 300/300 mg (6 × 300 mg) and 300/100 mg (2 × 300 mg followed by 4 × 100 mg) injections in treatment-seeking participants with moderate-to-severe OUD. Measures included the EQ-5D-5L, SF-36v2, Medication Satisfaction Questionnaire, employment/insurance status, and healthcare resource utilization (HCRU). Changes from baseline to end of study were compared across treatment arms, using mixed models for repeated measures. RESULTS: Participants receiving BUP-XR (n = 389) versus placebo (n = 98) had significantly greater changes from baseline on the EQ-5D-5L index (300/300 mg: difference = 0.0636, P = 0.003), EQ-5D-5L visual analog scale (300/300 mg: difference = 5.9, P = 0.017; 300/100 mg: difference = 7.7, P = 0.002), and SF-36v2 physical component summary score (300/300 mg: difference = 3.8, P < 0.001; 300/100 mg: difference = 3.2, P = 0.002). Satisfaction was significantly higher for participants receiving BUP-XR 300/300 mg (88%, P < 0.001) and 300/100 mg (88%, P < 0.001) than placebo (46%). Employment and percentage of insured participants increased by 10.8% and 4.1% with BUP-XR 300/300 mg and 10.0% and 4.7% with 300/100 mg but decreased by 12.6% and 8.4% with placebo. Participants receiving BUP-XR compared with placebo had significantly fewer hospital days per person-year observed. CONCLUSIONS: These results show the feasibility of measuring patient-centered life changes in substance use disorder clinical studies. Participants receiving up to 6 monthly injections of BUP-XR, compared with placebo, reported better health, increased medication satisfaction, increased employment, and decreased healthcare utilization.

The economic and clinical burden of early versus late initiation of celecoxib among patients with osteoarthritis.

OBJECTIVE: This study aimed to evaluate the characteristics associated with early versus late initiation of celecoxib treatment after osteoarthritis (OA) diagnosis and whether economic and safety outcomes differ between patients with early versus late initiation of celecoxib. METHODS: Adults (≥18 years) with a confirmed OA diagnosis (International Classification of Diseases, 9th Edition, Clinical Modifications code: 715.XX), ≥12 months of continuous pre- and post-index enrollment, and ≥1 post-index claim for celecoxib were included from the MarketScan® Commercial Claims and Encounter Database (2009-2013). Index date was defined as initial OA diagnosis. Patients were categorized as initiating celecoxib early (within 6 months of index date) or late (≥6 months after index date). Logistic regressions were used to assess characteristics associated with early versus late celecoxib initiation. Key outcomes included health care resource utilization (HCRU) and costs post-index, and adverse event incidence post-celecoxib initiation. Unadjusted and adjusted comparisons (using generalized linear models with a gamma distribution for costs and Poisson distribution for event and resource utilization) were made between early and late celecoxib initiators. RESULTS: Of the 62,434 OA patients identified, 27,402 were early and 35,032 were late initiators. Post-index hospital admissions and length of stay did not differ statistically between early versus late initiators after controlling for pre-index event rates and covariates, but early patients had significantly fewer outpatient (incidence rate ratio [IRR]: 0.96; 95% confidence interval [CI]: 0.95, 0.97) and emergency room visits (IRR: 0.89; 95% CI: 0.84, 0.95). After adjustment for key covariates, early initiators (versus late initiators) had lower all-cause (US$12,909 versus US$13,781, P<0.001) and OA-related (US$4,988 versus US$5,178, P=0.015) costs per person-year. Early initiators had no statistically significant difference in the incidence of post-celecoxib cardiovascular (IRR: 0.92; 95% CI: 0.73, 1.14), gastrointestinal (IRR: 1.25; 95% CI: 0.81, 1.92), or renal (IRR: 1.19; 95% CI: 0.65, 2.18) events, controlling for pre-index event rates and covariates when compared to late initiators. CONCLUSION: In this real-world cohort, patients initiated on celecoxib early (versus late) had significantly lower costs and HCRU; this may warrant consideration when making treatment decisions for OA patients.

Systematic review and benchmarking of Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) in oncology.

INTRODUCTION: The Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) has been used to evaluate the clinical benefits and risks of oncology treatments. However, limited information is available to interpret and contextualize Q-TWiST results. AREAS COVERED: A systematic review of Q-TWiST literature was conducted to provide contextualizing benchmarks for future studies. 51 articles with 81 unique Q-TWiST comparisons were identified. The mean (95% CI) and median absolute Q-TWiST gains for treatment versus control arms were 2.78 (1.82-3.73) months and 2.20 months across all cancers, respectively. The mean (median) relative Q-TWiST gains were 7.8% (7.2%) across all cancers. Most (88%) studies reported positive gains. The percentage of studies with relative Q-TWiST gains ≥10% (ie, clinically important difference) and ≥15% (ie, clearly clinically important difference) were 40.0% and 22.7%, respectively EXPERT COMMENTARY: The relevance of Q-TWiST in assessing net clinical benefits of cancer therapy has not diminished, despite an arguably low number of published studies. The interest in such assessment is highlighted by the recent emergence of oncology value frameworks. The Q-TWiST should be compelling to clinicians as it integrates clinical information (ie, toxicity, relapse/progression, and survival) and patient preferences for each of these states into a single meaningful index.

Treatment patterns, resource utilization, and outcomes among hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Lebanon and Saudi Arabia.

OBJECTIVES: To describe treatment patterns and medical resource use for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTI) in Saudi Arabia and Lebanon in terms of drug selection against the infecting pathogen as well as hospital resource utilization and clinical outcomes among patients with these infections. METHODS: This retrospective chart review study evaluated 2011-2012 data from five hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA cSSTI, which was culture-proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients with each infection type to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Statistical analysis was descriptive. RESULTS: Data were abstracted from medical records of 87 patients with MRSA cSSTI; mean age 52.4±25.9 years and 61% male. Only 64% of patients received an MRSA active initial therapy, with 56% of first-line regimens containing older beta-lactams. The mean total length of stay was 26.3 days, with the majority (19.1 days) spent in general wards. Surgical procedures included incision and drainage (22% of patients), debridement (14%), and amputation (5%). Mechanical ventilation was required by 9% of patients, with a mean duration of 18 days per patient. Hemodialysis was required by four patients (5%), two of whom were reported to have moderate to severe renal disease on admission, for a mean of 5.5 days. Inpatient mortality was 8%. Thirty-nine percent were prescribed at least one antibiotic at discharge, with the most commonly prescribed discharge antibiotics being clindamycin (44%), ciprofloxacin (18%), trimethoprim/sulfamethoxazole (12%), and linezolid (9%). CONCLUSION: This Middle Eastern real-world study of resource use and treatment patterns in MRSA cSSTI indicates that management of this condition could be further optimized in terms of drug selection and resource utilization.

Epidemiology and outcome of invasive fungal infections and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and complicated skin and soft tissue infections (cSSTI) in Lebanon and Saudi Arabia.

The objectives of this retrospective medical chart review study were to document the inpatient incidence, treatment, and clinical outcomes associated with invasive fungal infections (IFI) due to Candida and Aspergillus species, Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and MRSA complicated skin and soft tissue infections (cSSTI) in the Middle East. This study evaluated 2011-2012 data from 5 hospitals in Saudi Arabia and Lebanon with a combined total of 207,498 discharges. Hospital medical chart data were abstracted for a random sample of patients with each infection type (102 patients - IFI, 93 patients - MRSA pneumonia, and 87 patients-MRSA cSSTI). Descriptive analysis found that incidence of IFI (per 1000 hospital discharges) was higher than MRSA cSSTI and MRSA pneumonia (IFI: 1.95 and 2.57; MRSA cSSTI: 2.01 and 0.48; and MRSA pneumonia 0.59 and 0.55 for Saudi Arabia and Lebanon, respectively). Median time from hospital admission to diagnosis and from admission to initiation of active therapy were 6 and 7 days, respectively, in IFI patients; median time from admission to diagnosis was 2days for both MRSA pneumonia and cSSTI, with a median of 4 and 2days from admission to MRSA-active antibiotic start, respectively. The mean hospital LOS was 32.4days for IFI, 32.4days for MRSA pneumonia and 26.3days for MRSA cSSTI. Inpatient mortality was higher for IFI (42%) and MRSA pneumonia (30%) than for MRSA cSSTI (8%). At discharge, 33% of patients with IFI and 27% and 9% of patients with MRSA pneumonia and cSSTI, respectively, were considered to have failed therapy. In conclusion, there is a significant burden of these serious infections in the Middle East, as well as opportunity for hospitals to improve the delivery of patient care for difficult-to-treat infections by promoting expedited diagnosis and initiation of appropriate antimicrobial therapy.

Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis.

BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. RESULTS: Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months). CONCLUSIONS: Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.

Burden and treatment patterns of invasive fungal infections in hospitalized patients in the Middle East: real-world data from Saudi Arabia and Lebanon.

OBJECTIVES: The objective of this study was to document the burden and treatment patterns associated with invasive fungal infections (IFIs) due to Candida and Aspergillus species in Saudi Arabia and Lebanon. METHODS: A retrospective chart review study was conducted using data recorded from 2011 to 2012 from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of IFI due to Candida or Aspergillus, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Descriptive results were reported. RESULTS: Five hospitals participated and provided data on 102 patients with IFI (51 from Lebanon and 51 from Saudi Arabia). The mean age of the patients was 55 years, and 55% were males. Comorbidities included diabetes (41%), coronary artery disease (24%), leukemia (19%), moderate-to-severe renal disease (16%), congestive heart failure (15%), and chronic obstructive pulmonary disease (15%). Twenty percent of patients received corticosteroids prior to admission and 26% had received chemotherapy in the past 90 days. Inpatient mortality was 42%, and the mean hospital length of stay was 32.4±28.6 days. Fifty-five percent of patients required intensive care unit admission (17.2±14.1 days), 37% required mechanical ventilation (13.7±13.2 days), and 11% required dialysis (14.6±14.2 days). The most commonly used first-line antifungal was fluconazole. CONCLUSION: Patients with IFI in Saudi Arabia and Lebanon frequently have multiple medical comorbidities and may not have traditionally observed IFI risk factors. Efforts to increase use of rapid diagnostic tests and appropriate antifungal treatments may impact the substantial mortality and high length of stay observed in these patients.

Burden of methicillin-resistant Staphylococcus aureus pneumonia among hospitalized patients in Lebanon and Saudi Arabia.

OBJECTIVES: The objective of this study is to describe the real-world treatment patterns and burden of suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in Saudi Arabia and Lebanon. METHODS: A retrospective chart review study evaluated 2011-2012 data from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA pneumonia, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics (eg, age and comorbidities), treatment patterns (eg, timing and use of antimicrobials), hospital resource utilization (eg, length of stay), and clinical outcomes (eg, clinical status at discharge and mortality). Descriptive results were reported using frequencies or proportions for categorical variables and mean and standard deviation for continuous variables. RESULTS: Chart-level data were collected for 93 patients with MRSA pneumonia, 50 in Saudi Arabia and 43 in Lebanon. The average age of the patients was 56 years, and 60% were male. The most common comorbidities were diabetes (39%), congestive heart failure (30%), coronary artery disease (29%), and chronic obstructive pulmonary disease (28%). Patients most frequently had positive cultures from pulmonary (87%) and blood (27%) samples. All isolates were sensitive to vancomycin, teicoplanin, and linezolid, and only one-third of the isolates tested were sensitive to ciprofloxacin. Beta-lactams (inactive therapy for MRSA) were prescribed 21% of the time across all lines of therapy, with 42% of patients receiving first-line beta-lactams. Fifteen percent of patients did not receive any antibiotics that were considered to be MRSA active. The mean hospital length of stay was 32 days, and in-hospital mortality was 30%. CONCLUSION: The treatment for MRSA pneumonia in Saudi Arabia and Lebanon may be suboptimal with inactive therapy prescribed a substantial proportion of the time. The information gathered from this Middle East sample provides important perspectives on the current treatment patterns.

Dosing patterns and medication adherence in bipolar disorder patients treated with lurasidone: a US retrospective claims database analysis.

BACKGROUND: The aim of this study was to describe dosing patterns and medication adherence among bipolar patients who initiated lurasidone in a real-world setting. METHODS: Adult bipolar patients who initiated lurasidone between 1 November 2010 and 31 December 2012 (index period) with 6-month pre- and post-index continuous enrollment were identified from the IMS RWD Adjudicated Claims US database. Patients were grouped by starting lurasidone daily dose: 20 mg (7.1%), 40 mg (62.2%), 60-80 mg (28.7%), and 120-160 mg (2.1%). Patient characteristics were compared across doses using Cochran-Armitage trend tests. Multivariable ordinal logistic regression assessed the association between initial lurasidone dose and patient characteristics. Medication adherence was measured using medication possession ratio (MPR). RESULTS: Of 1114 adult bipolar patients (mean age 40.6 years, 70.6% female), 90% initiated lurasidone at 40 mg or 80 mg/day (mean 51.9 mg/day). Of these, 16.2% initiated lurasidone as monotherapy. Mean lurasidone maintenance dose was 55.2 mg/day and mean MPR was 0.53 [standard deviation (SD) = 0.34] over the 6-month follow up. Substance use, hyperglycemia, obesity, and prior antipsychotic use were associated with higher initial lurasidone doses (p < 0.05). Odds of a 20 mg/day increase in initial lurasidone dose was 1.6-times higher for patients with substance use [95% confidence interval (CI): 1.16-2.24], 2.6-times higher with hyperglycemia problems (95% CI: 1.15-5.83), 1.7-times higher with obesity (95% CI: 1.05-2.60), and 1.3 (95% CI: 1.01-1.78) and 1.8-times higher (95% CI: 1.17-2.86) with prior use of second- and first-generation antipsychotics, respectively. CONCLUSIONS: This real-world analysis of bipolar patients indicated that 40 mg or 80 mg/day were the most common starting doses of lurasidone. A majority of patients used concomitant psychiatric medications (polypharmacy). Higher doses of lurasidone were prescribed to patients with comorbidities or prior antipsychotic use. Adherence to lurasidone was comparable to or better than antipsychotic adherence reported in bipolar disorder literature.

Analysis of treatment patterns and persistence on branded and generic medications in major depressive disorder using retrospective claims data.

BACKGROUND: In major depressive disorder (MDD), treatment persistence is critical to optimize symptom remission, functional recovery, and health care costs. Desvenlafaxine tends to have fewer drug interactions and better tolerability than other MDD drugs; however, its use has not been assessed in the real world. OBJECTIVE: The aim of the present study is to compare medication persistence and concomitant MDD drug use with branded desvenlafaxine (Pristiq®) compared with antidepressant drug groups classified as 1) branded selective serotonin reuptake inhibitors (SSRIs; ie, escitalopram [Lexapro™]) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs; ie, venlafaxine [Effexor®], duloxetine [Cymbalta®]) and 2) generic SSRIs/SNRIs (ie, escitalopram, citalopram, venlafaxine, fluvoxamine, fluoxetine, sertraline, paroxetine, and duloxetine). PATIENTS AND METHODS: MDD patients (ICD-9-CM codes 296.2, 296.3), with ≥2 prescription fills for study drugs and 12-month preindex continuous enrollment from the MarketScan Commercial Claims and Encounters Database (2009-2013), were included. Time-to-treatment discontinuation (prescription gap ≥45 days) was assessed using the Kaplan-Meier curve and Cox model. Concomitant MDD drug use was compared. RESULTS: Of the 273,514 patients included, 14,379 patients were initiated with branded desvenlafaxine, 50,937 patients with other branded SSRIs/SNRIs, and 208,198 patients with generic SSRIs/SNRIs. The number of weeks for treatment discontinuation for branded desvenlafaxine were longer (40.7 [95% CI: 39.3, 42.0]) compared with other branded SSRIs/SNRIs (28.9 [95% CI: 28.4, 29.1]) and generic SSRIs/SNRIs (33.4 [95% CI: 33.1, 33.7]). Adjusting for baseline characteristics, patients who were prescribed with other branded SSRIs/SNRIs were 31% and generic SSRIs/SNRIs were 11% more likely to discontinue treatment compared with branded desvenlafaxine. In sensitivity analysis, the risk of discontinuation was within 10% of branded desvenlafaxine for branded duloxetine, generic escitalopram, and generic venlafaxine. Concomitant MDD drug use was higher among branded desvenlafaxine patients (43.8%) compared with other branded SSRIs/SNRIs (39.8%) and generic SSRIs/SNRIs (36.4%). CONCLUSION: MDD patients on branded desvenlafaxine were more persistent with treatment compared with those on other branded or generic SSRI/SNRI therapies. Future research should include assessments of underlying factors on the treatment persistence in MDD patients.

Impact of pulmonary exacerbations and lung function on generic health-related quality of life in patients with cystic fibrosis.

BACKGROUND: The analysis aimed to examine the impact of pulmonary exacerbations (PEs) and lung function on generic measures of HRQL in patients with cystic fibrosis (CF) using trial-based data. METHODS: In a 48-week randomized, placebo-controlled study of ivacaftor in patients ≥12 years with CF and a G551D-CFTR mutation the relationship between PEs, PE-related hospitalizations and percent predicted forced expiratory volume in one second (ppFEV1) with EQ-5D measures (index and visual analog scale [VAS]) was examined in post-hoc analyses. Multivariate mixed-effects models were employed to describe the association of PEs, PE-related hospitalizations, and ppFEV1 on EQ-5D measures. RESULTS: One hundred sixty one patients (age: mean 25.5 [SD 9.5] years; baseline ppFEV1: 63.6 [16.4]) contributed 1,214 observations (ppFEV1: no lung dysfunction [n = 157], mild [n = 419], moderate [n = 572], severe [n = 66]). Problems were most frequently reported on pain/discomfort, anxiety/depression, and usual activities EQ-5D items. The mean (SE) EQ-5D index nominally decreased (worsened) with worsening severity of lung dysfunction (P = 0.070): 0.931 (0.023); mild: 0.923 (0.021); moderate: 0.904 (0.018); severe: 0.870 (0.020). 146 PEs were experienced by 72 patients, including 52 PEs (35.6 %) that required hospitalization. Mean EQ-5D index and VAS scores were lowest (worst) within 1 week (before or after PE start) for PEs requiring hospitalization. Pulmonary exacerbations, PE-related hospitalizations, and ppFEV1 were significant predictors of EQ-5D index and VAS. CONCLUSIONS: In a clinical study of patients with CF (≥12 years of age and a G551D-CFTR mutation), PEs, primarily those requiring hospitalization, were associated with low EQ-5D index and VAS scores. The impact of ppFEV1 was relatively smaller. Reducing PEs, in particular those requiring hospitalization, would likely improve HRQL among these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00909532 ; URL: clinicaltrials.gov, May 26, 2009.