Post-traumatic stress in older, community-dwelling adults with hypertension during the COVID-19 pandemic: An investigation of pre-pandemic sociodemographic, health, and vascular and inflammatory biomarker predictors.

COVID-19 pandemic-related traumatic stress (PRTS) symptoms are reported in various populations, but risk factors in older adults with chronic medical conditions, remain understudied. We therefore examined correlates and pre-pandemic predictors of PRTS in older adults with hypertension during COVID-19. Participants in California, aged 61-92 years (n = 95), participated in a pre-pandemic healthy aging trial and later completed a COVID-19 assessment (May to September 2020). Those experiencing ⩾1 PRTS symptom (n = 40), and those without PRTS symptoms (n = 55), were compared. The PRTS+ group had poorer mental and general health and greater impairment in instrumental activities of daily living. Pre-pandemic biomarkers of vascular inflammation did not predict increased odds of PRTS; however, greater pre-pandemic anxiety and female gender did predict PRTS during COVID-19. Our findings highlight PRTS as a threat to healthy aging in older adults with hypertension; targeted approaches are needed to mitigate this burden, particularly for females and those with pre-existing anxiety.

Tai Chi versus health education as a frailty intervention for community-dwelling older adults with hypertension.

BACKGROUND: Frailty is associated with poor outcomes among older adults with hypertension and complicates its pharmacological management. Here, we assessed whether 12-weeks of instructor-guided, group Tai Chi (TC) practice improved frailty relative to Healthy Aging Practice-centered Education (HAP-E) classes in older adults with hypertension. METHODS: Secondary analysis of a randomized controlled trial in San Diego County, USA, of 167 community-dwelling individuals aged ≥ 60 yrs (70% female; 72.1 ± 7.5 yrs), defined as non-frail (66%) or frail (34%) based on 53-item deficit accumulation frailty index (FI). Linear mixed-effects models were used to assess pre-to-post intervention differences in FI and logistic regression to explore differential odds of clinically meaningful FI change. RESULTS: One hundred thirty-one participants completed post-intervention assessments. Frailty decreased pre-to-post intervention in the TC (ΔFI = - 0.016, d = - 0.39, - 0.75 to - 0.03), but not the HAP-E arm (ΔFI = - 0.009, d = - 0.13, - 0.52-0.27), despite no significant group differences between the TC and HAP-E arms (d = - 0.11, - 0.46-0.23). Furthermore, greater odds of improved FI were observed for frail participants in the TC (OR = 3.84, 1.14-14.9), but not the HAP-E (OR = 1.34, 0.39-4.56) arm. Subgroup analysis indicated treatment effects in TC were attributed to frail participants (frail: ΔFI = - 0.035, d = - 0.68, -1.26 to - 0.08; non-frail: ΔFI = - 0.005, d = - 0.19, - 0.59-0.22), which was not the case in the HAP-E arm (frail: ΔFI = - 0.017, d = - 0.23, - 0.81-0.35; non-frail: ΔFI = - 0.003, d = - 0.07, - 0.47-0.33). Frail participants were no more likely to drop-out of the study than non-frail (71% vs. 69% retained). CONCLUSIONS: Twelve weeks of twice-weekly guided TC practice was well-tolerated, associated with decreases in frailty, and increased odds of clinically meaningful FI improvement at post-intervention.

Tai chi or health education for older adults with hypertension: effects on mental health and psychological resilience to COVID-19.

OBJECTIVE: To compare the effectiveness of 12 weeks of community-based, in-person, group Tai Chi (TC) and Health Education (HAP-E) in improving health and wellbeing in older adults with hypertension and in promoting psychological resilience during COVID-19. METHODS: A 12-week randomized controlled trial (RCT) in San Diego County, USA. Self-reported depressive symptoms, anxiety, sleep disturbances, gratitude, resilience, mental and physical health were assessed in-person pre- and post-intervention, and by long-term follow-up surveys during COVID-19. Linear mixed-effects models were used to assess study arm differences over time and logistic regression to identify predictors of positive intervention response. RESULTS: Of 182 randomized participants (72.6 ± 7.9 yrs; 72% female), 131 completed the intervention. Modest improvements in health and wellbeing occurred post-intervention in both arms (Cohen's d: TC = 0.38, 95% CI: 0.25-0.51; HAP-E = 0.24, 0.11-0.37), though positive intervention responses were more than twice as likely in TC (OR = 2.29, 1.07-4.57). Younger age, higher anxiety, and poorer mental health at baseline predicted greater odds of response. Small declines in health and wellbeing were reported at the first COVID-19 follow-up, with smaller declines in the TC arm (Cohen's d: TC = -0.15, -0.31-0.00; HAP-E = -0.34, -0.49 to -0.19). Health and wellbeing stabilized at the second COVID-19 follow-up. Most participants (>70%) reported that the interventions benefitted their health and wellbeing during COVID-19. CONCLUSION: TC and HAP-E improved health and wellbeing, though TC conferred greater odds of an improved mental health response. Declines in health and wellbeing were observed at pandemic follow-up, with smaller declines in the TC arm, suggesting increased resilience.

Is Belonging to a Religious Organization Enough? Differences in Religious Affiliation Versus Self-ratings of Spirituality on Behavioral and Psychological Variables in Individuals with Heart Failure.

In the United States, heart failure (HF) affects approximately 6.5 million adults. While studies show that individuals with HF often suffer from adverse symptoms such as depression and anxiety, studies also show that these symptoms can be at least partially offset by the presence of spiritual wellbeing. In a sample of 327 men and women with AHA/ACC classification Stage B HF, we found that more spirituality in patients was associated with better clinically-related symptoms such as depressed mood and anxiety, emotional variables (affect, anger), well-being (optimism, satisfaction with life), and physical health-related outcomes (fatigue, sleep quality). These patients also showed better self-efficacy to maintain cardiac function. Simply belonging to a religious organization independent of spiritualty, however, was not a reliable predictor of health-related benefits. In fact, we observed instances of belonging to a religious organization unaccompanied by parallel spiritual ratings, which appeared counterproductive.

Effects of Caloric Intake and Aerobic Activity in Individuals with Prehypertension and Hypertension on Levels of Inflammatory, Adhesion and Prothrombotic Biomarkers-Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Cardiopulmonary fitness and low calorie diets have been shown to reduce inflammation but few studies have been conducted in individuals with elevated blood pressure (BP) in a randomized intervention setting. Thereby, adhesion biomarkers, e.g., soluble intercellular adhesion molecule (sICAM)-3, have not been examined so far. METHODS: Sixty-eight sedentary prehypertensive and mildly hypertensive individuals (mean age ± SEM: 45 ± 1 years; mean BP: 141/84 ± 1/1 mmHg) were randomized to one of three 12-week intervention groups: cardio training and caloric reduction, cardio training alone, or wait-list control group. Plasma levels of inflammatory, adhesion and prothrombotic biomarkers were assessed. In a second step, intervention groups were combined to one sample and multivariate regression analyses were applied in order to account for exercise and diet behavior changes. RESULTS: There were no significant differences among the intervention groups. In the combined sample, greater caloric reduction was associated with a larger increase of sICAM-3 (p = 0.026) and decrease of C-reactive protein (p = 0.018) as a result of the interventions. More cardio training was associated with increases of sICAM-3 (p = 0.046) as well as interleukin-6 (p = 0.004) and a decrease of tumor necrosis factor- (p = 0.017) levels. Higher BP predicted higher plasminogen activator inhibitor (PAI)-1 (p = 0.001), and greater fitness predicted lower PAI-1 levels (p = 0.006) after the intervention. CONCLUSIONS: In prehypertensive and hypertensive patients, plasma levels of the adhesion molecule sICAM-3 and inflammatory biomarkers have different response patterns to cardio training with and without caloric reduction. Such anti-inflammatory and anti-thrombotic effects may have implications for the prevention of atherothrombotic cardiovascular disease among individuals at increased risk.

Treatment patterns and costs among biologic-naive patients initiating apremilast or biologics for psoriatic arthritis.

Aim: We evaluated treatment patterns and healthcare costs of initiating psoriatic arthritis (PsA) treatment with oral apremilast versus biologics. Methods: Claims data identified biologic-naive adults with PsA who initiated either apremilast or a biologic from 2013 to 2016. Results: Medication adherence was similar at 12 months (76.9 vs 73.4%; p = 0.175) between apremilast (n = 381) and matched biologic (n = 761) patients. Apremilast users had $12,715 lower total costs per-patient-per-month (p < 0.001), largely due to outpatient pharmacy and medical costs. Conclusion: Commercially insured patients with PsA initiating apremilast had adherence similar to those initiating biologics but lower total healthcare costs.

Cost of peripheral neuropathy in patients receiving treatment for multiple myeloma: a US administrative claims analysis.

BACKGROUND: Peripheral neuropathy (PN) is a common consequence of multiple myeloma (MM) among those commonly treated with older-generation proteasome inhibitors (PIs). In this study, we evaluated the economic burden attributable to PN among MM patients in real-world practice settings in the US. METHODS: Adults diagnosed with MM and first treated (index event) between 1 July 2006 and 28 February 2017 were identified from MarketScan® Commercial and Medicare claim databases. Continuous enrollment for at least 12 months without treatment and PN diagnoses were required pre-index. Patients were followed for at least 3 months until inpatient death or end of data. The International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis codes were used to identify PN. Propensity-score matching was applied to match every patient with PN to two MM patients without a PN diagnosis (controls). Healthcare utilization and expenditures per patient per month (PPPM) in the postindex period were estimated. RESULTS: Of 11,851 patients meeting the study criteria, 15.5% had PN. After matching 1387 patients with PN and 2594 controls were identified. Baseline characteristics were well balanced between cohorts; mean follow up was 23-26 months. PPPM total costs were significantly higher by $1509 for patients with PN than controls, driven by higher hospitalization (PN 77.4%, controls 67.2%; p < 0.001) and emergency department rates (PN 67.8%, controls 58.4%; p < 0.001) and more outpatient hospital-based visits PPPM (PN 13.5 ± 14.7, controls 11.5 ± 18.0; p < 0.001). CONCLUSIONS: PN is a prevalent MM treatment complication associated with a significant economic burden adding to the complexity and cost of MM treatment. Highly effective novel treatments such as carfilzomib may reduce the overall disease burden.

Relationships among classifications of ayurvedic medicine diagnostics for imbalances and western measures of psychological states: An exploratory study.

BACKGROUND: According to Ayurveda, the traditional medical system of India, doshas are a combination of characteristics based on a five-element philosophy that drive our mental and physical tendencies. When the doshas, or functional principles, are out of balance in quality or quantity, wellbeing is adversely affected and symptoms manifest. OBJECTIVE: This study examined relationships among imbalances in the doshas (termed Vikruti) reported via questionnaire and Western measures of psychological states. MATERIALS AND METHODS: Study participants were 101 women (n = 81) and men (n = 20), mean age 53.9 years (SD = 11.7; range 32-80). Participants completed questionnaires to categorize their Vikruti type and psychological states, which included depressed mood (CESD), anxiety (PROMIS), rumination & reflection (RRQ), mindfulness (MAAS), stress (PSS), and quality of life (Ryff). RESULTS: Multivariate general linear modeling, controlling for age, gender and body mass index (BMI), showed that Vata imbalance was associated with more anxiety (p ≤ 0.05), more rumination (p ≤ 0.01), less mindfulness (p ≤ 0.05), and lower overall quality of life (p ≤ 0.01). Pitta imbalance was associated with poorer mood (p ≤ 0.01) and less mindfulness (p ≤ 0.05), more anxiety (p ≤ 0.05) and stress (p ≤ 0.05). Kapha imbalance was associated with more stress (p ≤ 0.05), more rumination (p ≤ 0.05) and less reflection (p ≤ 0.05). CONCLUSION: These findings suggest that symptoms of mind-body imbalances in Ayurveda are differentially associated with western assessments of psychological states. Ayurvedic dosha assessment may be an effective way to assess physical as well as emotional wellbeing in research and clinical settings.

Real-world US healthcare costs of psoriasis for biologic-naive patients initiating apremilast or biologics.

AIM: Biologics and apremilast have advanced psoriasis management by adding treatment options. This study evaluated persistence, adherence and healthcare costs among biologic-naive patients receiving apremilast or biologics. METHODS: Administrative claims data for adults starting apremilast or biologics from 1 January 2013 to 30 June 2016 were matched based on demographics. RESULTS: Apremilast (n = 703) and biologics (n = 1378) had similar baseline characteristics. 12-month persistence and adherence rates were similar. Adjusted total healthcare costs were lower with apremilast versus biologics (p < 0.001) due to lower total outpatient pharmacy costs (p < 0.001). CONCLUSION: Real-world apremilast users had similar adherence and lower total healthcare costs versus biologic users. Apremilast's cost advantage was evident regardless of whether the patients were persistent or nonpersistent, or switched or did not switch treatments.

Change in Sense of Nondual Awareness and Spiritual Awakening in Response to a Multidimensional Well-Being Program.

OBJECTIVE: This study examined the effects of a comprehensive mind-body program on sense of nondual awareness and spiritual awakening. DESIGN AND INTERVENTION: The study compared the effects of participation in an intensive 6-day Ayurveda-based mind-body program that addressed physical, emotional, and spiritual domains as compared with a control condition. SETTING: Resort setting. SUBJECTS: Participants were 69 healthy women and men (mean age 53.9 years; range 32-86). OUTCOME MEASURE: The primary outcome was the Nondual Embodiment Thematic Inventory (NETI). RESULTS: A significant group by time interaction (p = 0.029) indicated that after the intervention, participants in the mind-body program showed a significant increase in NETI scores (p < 0.03), which was sustained 1 month later (p < 0.01). CONCLUSION: Findings suggest that an intensive program providing holistic instruction and experience in mind-body practices can lead to a significant and sustained shift in perception of self-awareness, one that is likely favorable to well-being.

Prescribing Patterns of Oral Antineoplastic Therapies Observed in the Treatment of Patients With Advanced Prostate Cancer Between 2012 and 2014: Results of an Oncology EMR Analysis.

PURPOSE: The purpose of this study was to examine, using a US electronic medical records (EMR) database, the clinical characteristics and real-world treatment sequences in men with advanced prostate cancer who initiated treatment with abiraterone acetate or enzalutamide. METHODS: This retrospective, observational study evaluated adult male patients with a diagnosis of prostate cancer (International Classification of Diseases, Ninth Revision, Clinical Modification code 185) in the EMR database between July 1, 2011, and March 31, 2014, who had initiated first-line treatment with abiraterone acetate or enzalutamide between September 1, 2012, and March 31, 2014. The first record for a patient initiating abiraterone acetate or enzalutamide was the index date. Patients had 6 months of pre-index medical record history and a variable length follow-up period, extending from the index date to the end of medical record data availability or date of the end of the study (March 31, 2014). The sequence of first- and second-line therapies for advanced prostate cancer therapy was reported. FINDINGS: A total of 809 patients met study inclusion and exclusion criteria. This study found that the majority of patients who initiated treatment with either abiraterone acetate or enzalutamide between September 1, 2012, and March 31, 2014, received a single line of therapy (72%); abiraterone acetate was the most common first-line treatment (74% of first-line patients). A subset of patients treated first-line with either abiraterone acetate or enzalutamide were transitioned to an oral second-line agent (17% of first-line abiraterone acetate-treated patients transitioned to second-line enzalutamide, and 16% of first-line enzalutamide-treated patients transitioned to second-line abiraterone acetate). Chemotherapy with docetaxel was also a commonly observed second-line treatment selection, occurring in 8% of first-line abiraterone acetate-treated patients and in 7% of first-line enzalutamide-treated patients. IMPLICATIONS: This EMR study is among the first to present evidence of US physician practice prescribing patterns regarding initiation of oral antineoplastic agents and use of subsequent therapies in patients with advanced prostate cancer.

The Self-Directed Biological Transformation Initiative and Well-Being.

OBJECTIVE: To examine the effects of a comprehensive residential mind-body program on well-being. DESIGN: The Self-Directed Biological Transformation Initiative was a quasi-randomized trial comparing the effects of participation in a 6-day Ayurvedic system of medicine-based comprehensive residential program with a 6-day residential vacation at the same retreat location. SETTING: Retreat setting. PARTICIPANTS: 69 healthy women (n = 58) and men (n = 11) (mean age ± standard deviation, 53.6 ± 12 years). INTERVENTION: The Ayurvedic intervention addressed physical and emotional well-being through group meditation and yoga, massage, diet, adaptogenic herbs, lectures, and journaling. OUTCOME MEASURES: A battery of standardized questionnaires. RESULTS: Participants in the Ayurvedic program showed significant and sustained increases in ratings of spirituality (p < 0.01) and gratitude (p < 0.05) compared with the vacation group, which showed no change. The Ayurvedic participants also showed increased ratings for self-compassion (p < 0.01) as well as less anxiety at the 1-month follow-up (p < 0.05). CONCLUSIONS: Findings suggest that a short-term intensive program providing holistic instruction and experience in mind-body healing practices can lead to significant and sustained increases in perceived well-being and that relaxation alone is not enough to improve certain aspects of well-being.

Ustekinumab dosing, persistence, and discontinuation patterns in patients with moderate-to-severe psoriasis.

OBJECTIVES: Ustekinumab is the most recently approved biologic for the treatment of moderate-to-severe psoriasis. Real-world dosing patterns of ustekinumab are yet to be fully characterized. METHODS: A retrospective, observational study was conducted using MarketScan Commercial and Medicare databases. A cohort of psoriasis patients treated with ustekinumab between 25 September 2009 and 31 October 2010 was evaluated. Main outcomes included ustekinumab dosing and treatment patterns. Kaplan-Meier estimates were calculated to adjust for the censoring of data. Subgroup analysis was conducted for biologic-experienced patients and biologic-naïve patients. RESULTS: One thousand ustekinumab patients were included, of whom 60% were biologic-experienced. The average age was 49.0 and 53.9% were male. 63.3% of patients initiated ustekinumab with a 45 mg dose and 34.5% initiated with a 90 mg dose. Mean (median) days from initial dose to second dose was 31.1 (28.0). During maintenance therapy, dose intervals spanned from 80.6 to 81.2 (84.0) days. About 81.4% of patients were persistent during the variable-length follow-up period. CONCLUSIONS: The majority of patients received the 45 mg ustekinumab dose. The mean dosing intervals were consistent with the US prescribing guidelines. Biologic-naïve and biologic-experienced patients had similar dosing patterns. Ustekinumab treatment achieved a persistency rate as high as 81.4% over an average of 186.5 (SD 114.2) days of follow-up.

The inpatient experience and predictors of length of stay for patients hospitalized with systolic heart failure: comparison by commercial, Medicaid, and Medicare payer type.

OBJECTIVE: Descriptions of the inpatient experience for patients hospitalized with systolic heart failure (HF) are limited and lack a cross-sectional representation of the US population. While length of stay (LOS) is a primary determinant of resource use and post-discharge events, few models exist for estimating LOS. RESEARCH DESIGN AND METHODS: MarketScan(®) administrative claims data from 1/1/2005-6/30/2008 were used to select hospitalized patients aged ≥18 years with discharge diagnoses for both HF (primary diagnosis) and systolic HF (any diagnostic position) without prior HF hospitalization or undergoing transplantation. RESULTS: Among 17,597 patients with systolic HF; 4109 had commercial; 2118 had Medicaid; and 11,370 had Medicare payer type. Medicaid patients had longer mean LOS (7.1 days) than commercial (6.3 days) or Medicare (6.7 days). In-hospital mortality was highest for patients with Medicaid (2.4%), followed by Medicare (1.3%) and commercial (0.6%). Commercial patients were more likely to receive inpatient procedures. Renal failure, pressure ulcer, malnutrition, a non-circulatory index admission DRG, receipt of a coronary artery bypass procedure or cardiac catheterization, or need for mechanical ventilation during the index admission were associated with increased LOS; receipt of a pacemaker device at index was associated with shorter LOS. LIMITATIONS: Selection of patients with systolic HF is limited by completeness and accuracy of medical coding, and results may not be generalizable to patients with diastolic HF or to international populations. CONCLUSION: Inpatient care, LOS, and in-hospital survival differ by payer among patients hospitalized with systolic HF, although co-morbidity and inpatient procedures consistently influence LOS across payer types. These findings may refine risk stratification, allowing for targeted intensive inpatient management and/or aggressive transitional care to improve outcomes and increase the efficiency of care.

Effects of Aerobic Fitness and Adiposity on Coagulation Biomarkers in Men vs. Women with Elevated Blood Pressure.

A hypercoagulable state is a potential mechanism linking elevated blood pressure (BP), adiposity and a sedentary lifestyle to development of coronary heart disease (CHD). We examined relationships among aerobic fitness and adiposity in 76 sedentary subjects with elevated BP. Blood levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor (vWF) and thrombomodulin were assessed as biomarkers of coagulation. In individuals with elevated BP, percent body fat and fitness were associated with biomarkers indicative of a hypercoagulable state, even after demographic and metabolic factors were considered. D-dimer was positively associated with percent body fat (beta=0.37, p=0.003). PAI-1 was higher in men than in women (beta=-0.31, p=0.015) and associated with lower VO2peak (beta=-0.35, p=0.024). Thrombomodulin was positively associated with VO2peak (beta=0.56, p< 0.01). vWF was not significantly associated with fitness or adiposity. Our results emphasise that both percent body fat and physical fitness are important in the maintenance of haemostatic balance.

Rates and predictors of 30-day readmission among commercially insured and Medicaid-enrolled patients hospitalized with systolic heart failure.

BACKGROUND: Heart failure (HF) readmission rates are primarily derived from Medicare enrollees. Given increasing public scrutiny of HF readmissions, understanding the rate and predictors in populations covered by other payers is also important, particularly among patients with systolic dysfunction, for whom most HF-specific therapies are targeted. METHODS AND RESULTS: MarketScan Commercial and Medicaid Administrative Claims Databases were used to identify all first hospitalizations with an International Classification of Diseases-9 discharge diagnosis code for HF (primary position) and systolic HF (any position) between January 1, 2005, and June 30, 2008. Among 4584 unique systolic HF index admissions (mean age 55 years), 30-day crude readmission rates were higher for Medicaid than commercially insured patients: all-cause 17.4% versus 11.8%; HF-related 6.7% versus 4.0%, respectively. In unadjusted analysis, higher comorbidity and prior healthcare utilization predicted readmission; age, sex, and plan type did not. After adjustment for case mix, the odds of all-cause and HF-related readmission were 32% and 68% higher, respectively, among Medicaid than commercially insured patients (P<0.02 for both). No significant differences in readmission rates were seen for managed care versus fee-for-service or capitated versus noncapitated plan types. CONCLUSIONS: Compared with commonly cited Medicare HF readmission rates of 20% to 25%, Medicaid patients with systolic HF had lower 30-day readmission rates, and commercially insured patients had even lower rates. Even after adjustment for case mix, Medicaid patients were more likely to be readmitted than commercially insured patients, suggesting that more attention should be focused on readmissions among socioeconomically disadvantaged populations.

Incidence and cost of CAP in a large working-age population.

OBJECTIVES: To estimate incidence rates and quantify excess medical and productivity cost of community-acquired pneumonia (CAP) in a commercially insured, working-age population. METHODS: Using the Thomson Reuters MarketScan Commercial Claims and Encounters Database, we estimated the annual incidence of CAP from 2003 through 2007 and evaluated its excess direct medical and productivity costs due to short-term disability and workplace absenteeism for adult patients aged 18 to 64 years. A cohort of CAP patients was 1:3 propensity score matched to a control cohort without pneumonia. Both excess direct medical costs and excess productivity costs were estimated in multivariate ordinary least squares (OLS) and generalized linear model (GLM) adjusting for demographic and clinical characteristics. RESULTS: A total of 402,831 patients with CAP and 1,208,231 matched controls were included. Overall annual CAP incidence was 4.89 cases per 1000 person-years. Excess annual medical cost of CAP ranged from $7220 by OLS to $11,443 by GLM. Inpatient costs, outpatient costs, and pharmacy costs explained 34%, 51%, and 15% of this excess cost of the GLM models, respectively. CAP patients had an additional productivity cost of $2391. Among adults younger than 65 years, these estimates imply an incidence of CAP of 950,000 annual cases at a cost of $10.6 billion (range: $9.04-$13.1), of which 80% are direct medical costs and 20% are productivity costs. CONCLUSIONS: CAP is a frequent and costly event in a working-age population with a national cost of $10.6 billion. Interventions that could successfully prevent CAP could have a significant impact on healthcare costs and productivity.

Tumor necrosis factor blocker dose escalation among biologic naïve rheumatoid arthritis patients in commercial managed-care plans in the 2 years following therapy initiation.

OBJECTIVE: This study uses real-world US managed-care claims data to estimate dose escalation rates over the first and second years of therapy among biologic naïve rheumatoid arthritis (RA) patients initiating tumor necrosis factor (TNF) blocker therapy with etanercept, adalimumab, or infliximab. METHODS: Non-elderly adult (age 18-65 years) RA patients initiating etanercept, adalimumab, or infliximab from July 1, 2005 to April 30, 2009, were identified using the MarketScan Commercial Database. National and regional dose-escalation patterns were evaluated 12 and 24 months after initiation. In the single-instance method, dose escalation was defined as having one average weekly dose 115%, 130%, or 150% greater than the initial average weekly dose. By the two-instances method, dose escalation was defined as having two consecutive claims with an average weekly dose 115% or 130% greater than the initial average weekly dose. RESULTS: A total of 2747 patients met the inclusion criteria (mean age 50 years [SD=10]; 74% female). More patients initiated etanercept (44%) than adalimumab (37%) or infliximab (20%). Using the single-instance method, dose escalation at 12 months ranges were 0.8-1.5% for etanercept, 10.8-12.5% for adalimumab, and 16.4-42.5% for infliximab; ranges at 24 months were 0.8-2.1% for etanercept, 14.3-17.5% for adalimumab, and 26.4-57.6% for infliximab. The two-instances method showed a similar relationship among the treatment cohorts at both 12 and 24 months, with lower dose-escalation rates for etanercept (0.8%, 0.8%) than adalimumab (8.7%, 13.3%) or infliximab (22.9%, 37.6%) at the 130% threshold (p<0.001). Dose-escalation rates for etanercept, adalimumab, and infliximab were consistent across US geographic regions. CONCLUSION: Patients initiating etanercept had lower rates of dose escalation than patients initiating adalimumab or infliximab in the first and second year following therapy initiation, as well as across US geographic regions. These results may not be generalizable to the entire US RA population.

Formyl peptide receptors are candidate chemosensory receptors in the vomeronasal organ.

The identification of receptors that detect environmental stimuli lays a foundation for exploring the mechanisms and neural circuits underlying sensation. The mouse vomeronasal organ (VNO), which detects pheromones and other semiochemicals, has 2 known families of chemoreceptors, V1Rs and V2Rs. Here, we report a third family of mouse VNO receptors comprising 5 of 7 members of the formyl peptide receptor (FPR) family. Unlike other FPRs, which function in the immune system, these FPRs are selectively expressed in VNO neurons in patterns strikingly similar to those of V1Rs and V2Rs. Each FPR is expressed in a different small subset of neurons that are highly dispersed in the neuroepithelium, consistently coexpress either G alpha(i2) or G alpha(o), and lack other chemoreceptors examined. Given the presence of formylated peptides in bacteria and mitochondria, possible roles for VNO FPRs include the assessment of conspecifics or other species based on variations in normal bacterial flora or mitochondrial proteins.

Sperm plasma membrane breakdown during Drosophila fertilization requires sneaky, an acrosomal membrane protein.

Fertilization typically involves membrane fusion between sperm and eggs. In Drosophila, however, sperm enter eggs with membranes intact. Consequently, sperm plasma membrane breakdown (PMBD) and subsequent events of sperm activation occur in the egg cytoplasm. We previously proposed that mutations in the sneaky (snky) gene result in male sterility due to failure in PMBD. Here we support this proposal by demonstrating persistence of a plasma membrane protein around the head of snky sperm after entry into the egg. We further show that snky is expressed in testes and encodes a predicted integral membrane protein with multiple transmembrane domains, a DC-STAMP-like domain, and a variant RING finger. Using a transgene that expresses an active Snky-Green fluorescent protein fusion (Snky-GFP), we show that the protein is localized to the acrosome, a membrane-bound vesicle located at the apical tip of sperm. Snky-GFP also allowed us to follow the fate of the protein and the acrosome during fertilization. In many animals, the acrosome is a secretory vesicle with exocytosis essential for sperm penetration through the egg coats. Surprisingly, we find that the Drosophila acrosome is a paternally inherited structure. We provide evidence that the acrosome induces changes in sperm plasma membrane, exclusive of exocytosis and through the action of the acrosomal membrane protein Snky. Existence of testis-expressed Snky-like genes in many animals, including humans, suggests conserved protein function. We relate the characteristics of Drosophila Snky, acrosome function and sperm PMBD to membrane fusion events that occur in other systems.