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Anuj Shah,1 Xinyi Ng,1 Ruchit Shah,1 Caitlyn Solem,1 Ping Wang,2 Marko Obradovic3 1Patient Centered Outcomes, Pharmerit – An OPEN Health Company, Bethesda, MD, USA; 2Health Economics and Outcomes Research, Insmed Incorporated, Bridgewater Township, NJ, USA; 3Health Economics and Outcomes Research, Insmed Germany GmbH, Frankfurt am Main, GermanyCorrespondence: Marko ObradovicSenior Director, HEOR Europe, Insmed Germany GmbH, The Square 12, am Flughafen, Frankfurt (Frankfurt am Main), 60549, GermanyEmail marko.obradovic@insmed.comPurpose: This analysis evaluated the psychometric properties of the EQ-5D-3L among patients with Mycobacterium avium complex lung disease (MAC-LD).Methods: Data from the Phase III CONVERT trial were analyzed. Study measures including the EQ-5D-3L, St. George’s Respiratory Questionnaire (SGRQ), the 6-minute walk test (6MWT), and percent predicted forced expiratory volume in 1 second (ppFEV1) were collected at baseline, month 3 (M3), month 4 (M4; only 6MWT), and month 6 (M6). Item characteristics and validity were evaluated at baseline. Test–retest reliability was assessed using intraclass correlation coefficients (ICC) and a weighted kappa statistic among a subgroup of stable patients. Validity was tested by evaluating correlations of the EQ-5D-3L index/visual analogue scale (VAS) scores with SGRQ and 6MWT and comparing mean index/VAS scores across known groups defined using 6MWT and ppFEV1. Responsiveness of the EQ-5D-3L was assessed using 6MWT, SGRQ, ppFEV1, and culture conversion as anchors.Results: The index score was subject to ceiling effects, with 32.6% of patients reporting perfect health at baseline. ICCs for the index (0.80) and VAS (0.85) scores and weighted kappas for the domains (0.5– 0.72) indicated adequate test–retest reliability. Correlations between the index/VAS scores and related domains of the SGRQ and 6MWT were as hypothesized (0.31– 0.62), and the mean index/VAS scores were significantly different between the 6MWT and ppFEV1 known groups (p< 0.05), supporting the validity of the EQ-5D-3L. No evidence was found supporting the responsiveness of the EQ-5D-3L to changes in any of the anchors.Conclusion: EQ-5D-3L exhibited evidence of validity and reliability but poor responsiveness to clinically meaningful changes in patients with MAC-LD.Keywords: psychometric validation, NTM lung disease, EQ-5D, reliability, validity, responsiveness

Katharina Verleger, 1 John R Penrod, 2 Melinda Manley Daumont, 3 Caitlyn Solem, 4 Linlin Luo, 4 Cynthia Macahilig, 5 Nadine Hertel 6 1Pharmerit International, Berlin, Germany; 2Bristol-Myers Squibb, Princeton, NJ, USA; 3Bristol-Myers Squibb, Braine-L’alleud, Belgium; 4Pharmerit International, Bethesda, MD, USA; 5Medical Data Analytics, Parsippany, NJ, USA; 6Bristol-Myers Squibb, Uxbridge, UKCorrespondence: Katharina VerlegerPharmerit International, Krausenstr 8, Berlin 10117, GermanyTel +49 30 3080 7024Email kverleger@pharmerit.comPurpose: Advanced non-small-cell lung cancer (aNSCLC; stage IIIB/IV) presents a substantial clinical burden to society; reliable estimates of its economic burden are lacking. Therefore, this study aimed to quantify real-world health care resource utilization (HCRU) and costs of patients with squamous (SQ) and non-SQ (NSQ) aNSCLC who received two or more lines of treatment (2L+) in Europe, and to describe cost-predictors.Methods: The LENS (Leading the Evaluation of Non-squamous and Squamous NSCLC) retrospective chart review study collected data from 2L+ patients with aNSCLC diagnosed between 07/2009 and 08/2011 (wave 1) or 07/2010 and 09/2012 (wave 2) in France, Germany, Italy, Spain, England, the Netherlands, and Sweden. Patients were followed from diagnosis through most recent visit/death. A weighted average of country-specific unit costs (2018 Euro) was applied to systemic anti-cancer therapy usage and HCRU (hospital/emergency department visit, surgery, radiotherapy, ancillary care, biomarker testing) to determine the total cost from aNSCLC diagnosis to death. Generalized linear models (gamma distribution, log link) were used to assess clinical and demographic predictors.Results: Of 973 2L+ aNSCLC patients, median overall survival (OS) was 1.5 years from advanced diagnosis (range: 0.2– 5.3; median OS: 1.4 [SQ], 1.6 [NSQ]), 79.0% died during follow-up. Weighted mean total per-patient costs were € 21,273, ranging from € 17,761 (England) to € 30,854 (Sweden), and € 15,446 (SQ) to € 26,477 (NSQ). Systemic drug costs comprised 77.4% of total costs. Insurance status, presence of epidermal growth factor receptor (EGFR) mutation, SQ histology, age, alcohol abuse, and year of diagnosis were significant predictors for lower total costs per patient-month, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 1 and country for higher costs.Conclusion: In the era pre-immunotherapy, HCRU and costs were substantial in aNSCLC 2L+ patients, with most of the costs accrued prior to start of 2L. NSQ patients incurred significantly higher total costs than SQ patients in all participating countries.Keywords: carcinoma, non-small-cell lung, observational study, cost of illness, health care costs

BACKGROUND: Catheter-related bloodstream infections (BSIs) are a serious problem leading to increased morbidity, longer hospital stay, and hence, additional costs. This study evaluated the risk of BSI and the cost of parenteral nutrition (PN) in Germany. SUBJECTS/METHODS: A retrospective observational chart review of patients hospitalized from October 2009 to April 2011 and receiving PN via ready-to-use three-chamber bag (MCB), single bottle (SB) or hospital compounded admixture (CPN) was conducted across Germany. Propensity score-adjusted models were used to evaluate the association between the type of PN, BSI (Cox Proportional Hazards) and hospitalization cost (generalized linear models) within a subgroup receiving all three macronutrients (lipids, amino acids, glucose). RESULTS: Of the 1995 patient records reviewed (MCB = 816; CPN = 584; SB = 595), 1457 patients received all three macronutrients. After adjustment, SB was associated with an increased hazard of BSI, vs MCB without additions (hazard ratio (HR) (95% confidence interval (CI)) = 2.53 (1.66-3.86)) in the total cohort. Adding supplements to MCB on the ward also increased the BSI risk in both total and subgroup analyses. In patients receiving all three macronutrients, adjusted total costs were MCB (no additions): 6,572 € (95% CI: 6,896 €-6263); CPN: 6,869 € (7,283 €-6479); SB: 6,872 € (7,242 €-6521); MCB (ward additions): 7,402 € (7,878 €-6955); P < 0.001; P < 0.001. CONCLUSION: Use of MCB does not appear to increase treatment costs, possibly by reducing the risk of infection. This study identified several PN preparation methods associated with a significantly increased hazard for BSI; definitive CPN findings are limited by our inability to distinguish automated from manual pharmacy compounding. European Journal of Clinical Nutrition (2014) 68, 953-958; doi: 10.1038/ejcn.2014.34; published online 26 March 2014, INTRODUCTION Parenteral nutrition (PN) is a life-saving therapy for patients with intestinal failure and may be critically important for trauma patients, those with inflammatory bowel disease, gastrointestinal fistulae, pancreatitis, pre-term [...]

Rahul Dhanda,1 Della Varghese,2 Vijay R Nadipelli,1 Maurizio Fava,3 Namita Joshi,2 Caitlyn T Solem,2 James A Graham,4 Susan M Learned,4 Christian Heidbreder51Global Health Economics and Outcomes Research, Indivior Inc, Richmond, VA 23235, USA; 2Real-World Evidence and Data Analytics, Pharmerit International, Bethesda, MD 20814, USA; 3Clinical Trials Network Institute (CTNI), Massachusetts General Hospital (MGH) and Harvard Medical School, Boston, MA 02114, USA; 4Global Medicines Development, Indivior Inc, Richmond, VA 23235, USA; 5Global Research and Development, Indivior Inc, Richmond, VA 23235, USAPurpose: 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.Keywords: antipsychotics, quality of life, medication satisfaction, medication preference, clinical trial

Walter Ling,1 Vijay R Nadipelli,2 Caitlyn T Solem,3 David Farabee,1,4 Naoko A Ronquest,2 Brian Perrochet,1,5 Susan M Learned,6 Chinmay G Deshpande,3 Christian Heidbreder71UCLA Department of Family Medicine, Center for Behavioral and Addiction Medicine, Los Angeles, CA, USA; 2Global Health Economics and Outcomes Research, Indivior Inc, Richmond, VA, USA; 3Patient-centered outcomes Center of Excellence, Pharmerit International, Bethesda, ML, USA; 4Department of Population Health, School of Medicine,, New York, NY, USA; 5Marron Institute of Urban Management, Marron Institute, New York University, New York, NY, USA; 6Global Medicines Development, Indivior Inc, Richmond, VA, USA; 7Global Research and Development, Indivior Inc, Richmond, VA, USAPurpose: 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

Ahmed Shelbaya,1,2 Caitlyn T Solem,3 Chris Walker,4 Yin Wan,3 Courtney Johnson,3 Joseph C Cappelleri1 1Pfizer Inc., New York, NY, 2Columbia School of Public Health, New York, NY, 3Pharmerit International, Bethesda, MD, USA; 4Pfizer Ltd., Tadworth, Surrey, UK 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

Abdulhakeem O Althaqafi,1 Madonna J Matar,2 Rima Moghnieh,3 Adel F Alothman,4 Thamer H Alenazi,5 Fayssal Farahat,1 Shelby Corman,6 Caitlyn T Solem,6 Nirvana Raghubir,7 Cynthia Macahilig,8 Seema Haider,9 Jennifer M Stephens6 1Department of Infection Prevention and Control, King Abdullah International Medical Research Center, King Saud bin AbdulAziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia; 2Department of Infectious Disease, Notre Dame de Secours University Hospital, Byblos, 3Makassed General Hospital, Beirut, Lebanese Republic; 4Department of Medicine, King Abdulaziz Medical City, Central Region, Ministry of National Guard Health Affairs, 5Infection Prevention & Control Department, King Abdulaziz Medical City-Riyadh (KAMC), Kingdom of Saudi Arabia; 6Real World Evidence: Data Analytics Center of Excellence, Pharmerit International, Bethesda, MD, 7Medical Affairs, Pfizer, New York, NY, 8Medical Data Analytics, Parsippany, NJ, 9Outcomes & Evidence, Global Health and Value, Pfizer, Groton, CT, USA 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. Keywords: MRSA, resource use, mortality, length of stay, antibiotics, Middle East

Madonna J Matar,1 Rima Moghnieh,2 Adel F Alothman,3 Abdulhakeem O Althaqafi,4 Thamer H Alenazi,3 Fayssal M Farahat,4 Shelby Corman,5 Caitlyn T Solem,5 Nirvana Raghubir,6 Cynthia Macahilig,7 Seema Haider,8 Jennifer M Stephens5 1Department of Infectious Diseases, Notre Dame des Secours University Hospital, Jbeil, Lebanon; 2Department of Internal Medicine, Makassed General Hospital, Beirut, Lebanon; 3College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 4King Abdullah International Medical Research Center, Infection Prevention and Control, King AbdulAziz Medical City, King Saud bin AbdulAziz University for Health Sciences, Jeddah, Saudi Arabia; 5Pharmerit International, Real-World Evidence/Data Analytics, Bethesda, MD, 6Pfizer, New York, NY, 7Medical Data Analytics, Parsippany, NJ, 8Pfizer, Groton, CT, USA 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. Keywords: antibiotics, length of stay, Saudi Arabia, Lebanon, skin, skin structure infections

Adel F Alothman,1 Abdulhakeem O Althaqafi,2 Madonna J Matar,3 Rima Moghnieh,4 Thamer H Alenazi,1 Fayssal M Farahat,2 Shelby Corman,5 Caitlyn T Solem,5 Nirvana Raghubir,6 Cynthia Macahilig,7 Claudie Charbonneau,8 Jennifer M Stephens5 1College of Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Department of Infection Prevention and Control, King Abdullah International Medical Research Center, King Saud bin AbdulAziz University for Health Sciences, King AbdulAziz Medical City, Jeddah, Saudi Arabia; 3Department of Infectious Disease, Notre Dame de Secours University Hospital, Byblos, Lebanon; 4Department of Internal Medicine, Makassed General Hospital, Beirut, Lebanon; 5Real-world Evidence/Data Analytics Center of Excellence, Pharmerit International, Bethesda, MD, USA; 6Pfizer, New York, NY, 7Medical Data Analytics, Parsippany, NJ, USA; 8Pfizer International Operation, Paris, France 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. Keywords: Candida, Aspergillus, length of stay, resource use, antifungal, mortality

Caitlyn T Solem,1 Ahmed Shelbaya,2,3 Yin Wan,1 Chinmay G Deshpande,1 Jose Alvir,2 Elizabeth Pappadopulos2 1Pharmerit International, Real World Evidence/Data Analytics, Bethesda, MD, 2Pfizer, Inc., Global Health Outcomes, New York, NY, 3Epidemiology Department of Mailman’s School of Public Health, Columbia University Mailman School of Public Health, New York, NY, USA 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. Keywords: selective serotonin reuptake inhibitors, selective serotonin–norepinephrine re-uptake inhibitors

Ashraf El Houfi,1 Nadeem Javed,2 Caitlyn T Solem,3 Cynthia Macahilig,4 Jennifer M Stephens,3 Nirvana Raghubir,5 Richard Chambers,6 Jim Z Li,7 Seema Haider81Dubai Hospital, Dubai, UAE; 2Rashid Hospital, Dubai, UAE; 3Pharmerit International, Bethesda, MD, USA; 4Medical Data Analytics, Parsippany, NJ, USA; 5Pfizer, New York, NY, USA; 6Pfizer, Collegeville, PA, USA; 7Pfizer, La Jolla, CA, USA; 8Pfizer, Groton, CT, USAObjectives: To describe real-world treatment patterns and health care resource use and to estimate opportunities for early-switch (ES) from intravenous (IV) to oral (PO) antibiotics and early-discharge (ED) for patients hospitalized in the United Arab Emirates (UAE) with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections.Methods: This retrospective observational medical chart review study enrolled physicians from four UAE sites to collect data for 24 patients with documented MRSA complicated skin and soft tissue infections, hospitalized between July 2010 and June 2011, and discharged alive by July 2011. Data include clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and PO antibiotic use, and ES and ED eligibility using literature-based and expert-validated criteria.Results: Five included patients (20.8%) were switched from IV to PO antibiotics while being inpatients. Actual length of MRSA-active treatment was 10.8±7.0 days, with 9.8±6.6 days of IV therapy. Patients were hospitalized for a mean 13.9±9.3 days. The most frequent initial MRSA-active therapies used were vancomycin (37.5%), linezolid (16.7%), and clindamycin (16.7%). Eight patients were discharged with MRSA-active antibiotics, with linezolid prescribed most frequently (n=3; 37.5%). Fifteen patients (62.5%) met ES criteria and potentially could have discontinued IV therapy 8.3±6.0 days sooner, and eight (33.3%) met ED criteria and potentially could have been discharged 10.9±5.8 days earlier.Conclusion: While approximately one-fifth of patients were switched from IV to PO antibiotics in the UAE, there were clear opportunities for further optimization of health care resource use. Over half of UAE patients hospitalized for MRSA complicated skin and soft tissue infections could be eligible for ES, with one-third eligible for ED opportunities, resulting in substantial potential for reductions in IV days and bed days.Keywords: IV-to-PO switch, length of stay, clinical criteria, antibiotic therapy, economics

Caitlyn T Solem,1 Shawn X Sun,2 Sizhu Liu,1 Cynthia Macahilig,3 Monica Katyal,3 Xin Gao,1 Andrew F Shorr4 1Pharmerit International, Bethesda, MD, 2Forest Research Institute, Jersey City, NJ, 3Medical Data Analytics, Parsippany, NJ, 4Pulmonary Critical Care, Washington Hospital Center and Georgetown University, Washington, DC, USA Objective: This study aimed to compare spirometry- and risk + symptom-based classification systems to physician-based severity assessment and find which system is most predictive of patient-reported health status, as measured by the St George's Respiratory Questionnaire for COPD (chronic obstructive pulmonary disease; SGRQ-C).Materials and methods: In this chart review/patient survey, 99 physicians recruited patients with physician-assessed severe or very severe COPD who had recently experienced a moderate or severe exacerbation. A cross-tabulation was undertaken comparing physician report, spirometry (mild/moderate, forced expiratory volume in 1 second [FEV1] ≥50%; severe, 30% ≤ FEV1

Caitlyn T Solem,1 Shawn X Sun,2 Lavanya Sudharshan,1 Cynthia Macahilig,3 Monica Katyal,3 Xin Gao1 1Pharmerit International, Bethesda, MD, USA; 2Forest Research Institute, Jersey City, NJ, USA; 3Medical Data Analytics, Parsippany, NJ, USA Purpose: Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined. This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype. Patients and methods: A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited. Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]). The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions. Results: A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included. In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations. Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%). Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006). The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P

Azza AbuDagga,1 Shawn X Sun,2 Hiangkiat Tan,1 Caitlyn T Solem3 1HealthCore Inc, Wilmington, DE, 2Forest Research Institute, Jersey City, NJ, 3Pharmerit North America, Bethesda, MD, USA Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are the leading cause of hospital admission and death among chronic bronchitis (CB) patients. This study estimated annual COPD exacerbation rates, related costs, and their predictors among patients treated for CB. Methods: This was a retrospective study using claims data from the HealthCore Integrated Research Database (HIRDSM). The study sample included CB patients aged ≥ 40 years with at least one inpatient hospitalization or emergency department visit or at least two office visits with CB diagnosis from January 1, 2004 to May 31, 2011, at least two pharmacy fills for COPD medications during the follow-up year, and ≥2 years of continuous enrollment. COPD exacerbations were categorized as severe or moderate. Annual rates, costs, and predictors of exacerbations during follow-up were assessed. Results: A total of 17,382 individuals treated for CB met the selection criteria (50.6% female; mean ± standard deviation age 66.7 ± 11.4 years). During the follow-up year, the mean ± standard deviation number of COPD maintenance medication fills was 7.6 ± 6.3; 42.6% had at least one exacerbation and 69.5% of patients with two or more exacerbations during the 1 year prior to the index date (baseline period) had any exacerbation during the follow-up year. The mean ± standard deviation cost per any exacerbation was $269 ± $748 for moderate and $18,120 ± $31,592 for severe exacerbation. The number of baseline exacerbations was a significant predictor of the number of exacerbations and exacerbation costs during follow-up. Conclusion: Exacerbation rates remained high among CB patients despite treatment with COPD maintenance medications. New treatment strategies, designed to reduce COPD exacerbations and associated costs, should focus on patients with high prior-year exacerbations. Keywords: chronic bronchitis, chronic obstructive pulmonary disease, exacerbations, maintenance medications, managed care

Guy Young,1 Caitlyn T Solem,2,3 Kate Hoffman,4 Jenna Kabawat,4 A Simon Pickard,3 Robert Z Gut,5 David L Cooper51Children's Center for Cancer and Blood Disorders, Children's Hospital Los Angeles, Los Angeles, CA, 2Pharmerit, Bethesda, MD, 3Center for Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL, 4Outcome Sciences, Cambridge, MA, 5Novo Nordisk Inc, Princeton, NJ, USAObjective: The daily recordings of treatment by patients with congenital hemophilia with inhibitors and their caregivers were assessed as part of the Dosing Observational Study in Hemophilia (DOSE) to understand the patterns of bypassing agent use and health-related quality of life.Methods: Frequently bleeding patients prescribed recombinant activated factor VII as first-line therapy were eligible. Participants recorded daily paper diaries for at least 90 days and until at least four bleeding episodes had occurred. Web-based entry was optional. Assessment included bleeding status, work or school day status, bleeding episode, treatment, impact on planned activities, and health-related quality of life.Results: Diaries were completed by 18 adults and 19 caregivers (21 children). A total of 4063 diary days and 194 bleeding episodes over 491 bleed days were recorded. A small proportion of diary days were bleed days (8.2%) or treatment days (8.2%). Half the bleed days were not planned work or school days for patients (53%) or caregivers (48%). An exact agreement was observed between electronic and paper records for 93% of the reviewed health-related quality of life measurements.Conclusion: Daily diary completion by patients and caregivers is feasible and provides insight into the impact of congenital hemophilia with inhibitors on daily activities and overall quality of life. Positive participation and completion rates were supported by frequent patient contact made by independent patient support liaison personnel.Keywords: daily assessment, recombinant activated factor VII, rFVIIa, NovoSeven, quality of life

Lactococcus lactis suffers from oxidative stress and riboflavin starvation at elevated temperatures due to dissolved oxygen, which can be relieved partially by exogenously supplied riboflavin. Here we explore whether this phenomenon can be harnessed to obtain riboflavin overproducing mutants. Using a riboflavin auxotrophic L. lactis strain as a riboflavin biosensor, we screened L. lactis cultures that had been exposed to temperature induced oxidative stress for up to one year. Riboflavin secreting mutants could readily be identified, some of which had arisen after just two weeks of exposure to oxidative stress. Whole genome sequencing revealed mutations in the riboswitch, which regulate riboflavin biosynthesis. Riboflavin secretion conferred a significant increase in tolerance to oxidative stress and enabled growth at high temperatures in the presence of dissolved oxygen. It was subsequently demonstrated that vigorous aeration at high temperature (37 °C) could prompt rapid emergence of riboflavin secreting mutants. The protective effect provided by riboflavin against oxidative stress may explain the natural occurrence of lactic acid bacteria (LAB) secreting riboflavin. By optimizing fermentation conditions and eliminating lactate formation, we achieved 64 mg/L riboflavin, the highest reported titer so far for LAB, which indicates great potential for use as a riboflavin fortification agent in food.

Due to the reports describing virulent and multidrug resistant enterococci, their use has become a topic of controversy despite most of them being safe and commonly used in traditionally fermented foods worldwide. We have characterized Enterococcus lactis SF68, a probiotic strain approved by the European Food Safety Authority (EFSA) for use in food and feed, and find that it has a remarkable potential in food fermentations. Genome analysis revealed the potential of SF68 to metabolize a multitude of carbohydrates, including lactose and sucrose, which was substantiated experimentally. Bacteriocin biosynthesis clusters were identified and SF68 was found to display a strong inhibitory effect against Listeria monocytogenes . Fermentation-wise, E. lactis SF68 was remarkably like Lactococcus lactis and displayed a clear mixed-acid shift on slowly fermented sugars. SF68 could produce the butter aroma compounds, acetoin and diacetyl, the production of which was enhanced under aerated conditions in a strain deficient in lactate dehydrogenase activity. Overall, E. lactis SF68 was found to be versatile, with a broad carbohydrate utilization capacity, a capacity for producing bacteriocins, and an ability to grow at elevated temperatures. This is key to eliminating pathogenic and spoilage microorganisms that are frequently associated with fermented foods.

Enterococci comprise a group of lactic acid bacteria (LAB) with considerable potential to serve as food fermentation microorganisms. Unfortunately, enterococci have received a lot of negative attention, due to the occurrence of pathogenic and multidrug resistant strains. In this study, we used genomics to select safe candidates among the forty-four studied enterococcal isolates. The genomes of the forty-four strains were fully sequenced and assessed for presence of virulence and antibiotic resistance genes. Nineteen isolates belonging to the species Enterococcus lactis, Enterococcus faecium, Enterococcus durans, and Enterococcus thailandicus, were deemed safe from the genome analysis. The presence of secondary metabolite gene clusters for bacteriocins was assessed, and twelve candidates were found to secrete antimicrobial compounds effective against Listeria monocytogenes isolated from cheese and Staphylococcus aureus. Physiological characterization revealed nineteen industrial potentials; all strains grew well at 42 °C and acidified 1.5 hours faster than their mesophilic counterpart Lactococcus lactis, with which they share metabolism and flavor forming ability. We conclude that a large fraction of the examined enterococci were safe and could serve as excellent food fermentation microorganisms with inherent bioprotective abilities., Competing Interests: Conflicts of interest There are no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)