Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Exacerbations among chronic bronchitis patients treated with maintenance medications from a US managed care population: an administrative claims data analysis

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 car

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

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<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. Keywords: osteoarthritis, celecoxib, nonsteroidal anti-inflammatory drug, economic burden, health care resource use&nbsp

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

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 inhibitor

Early-switch/early-discharge opportunities for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections: proof of concept in the United Arab Emirates

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, economic

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

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, mortalit

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

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 Eas