Applying an Innovative Model of Disaster Resilience at the Neighborhood Level : The COPEWELL New York City Experience.

Community resilience is a community's ability to maintain functioning (ie, delivery of services) during and after a disaster event. The Composite of Post-Event Well-Being (COPEWELL) is a system dynamics model of community resilience that predicts a community's disaster-specific functioning over time. We explored COPEWELL's usefulness as a practice-based tool for understanding community resilience and to engage partners in identifying resilience-strengthening strategies. In 2014, along with academic partners, the New York City Department of Health and Mental Hygiene organized an interdisciplinary work group that used COPEWELL to advance cross-sector engagement, design approaches to understand and strengthen community resilience, and identify local data to explore COPEWELL implementation at neighborhood levels. The authors conducted participant interviews and collected shared experiences to capture information on lessons learned. The COPEWELL model led to an improved understanding of community resilience among agency members and community partners. Integration and enhanced alignment of efforts among preparedness, disaster resilience, and community development emerged. The work group identified strategies to strengthen resilience. Searches of neighborhood-level data sets and mapping helped prioritize communities that are vulnerable to disasters (eg, medically vulnerable, socially isolated, low income). These actions increased understanding of available data, identified data gaps, and generated ideas for future data collection. The COPEWELL model can be used to drive an understanding of resilience, identify key geographic areas at risk during and after a disaster, spur efforts to build on local metrics, and result in innovative interventions that integrate and align efforts among emergency preparedness, community development, and broader public health initiatives.

Primary Care Emergency Preparedness Network, New York City, 2015: Comparison of Member and Nonmember Sites.

OBJECTIVES: To assess whether Primary Care Emergency Preparedness Network member sites reported indicators of preparedness for public health emergencies compared with nonmember sites. The network-a collaboration between government and New York City primary care associations-offers technical assistance to primary care sites to improve disaster preparedness and response. METHODS: In 2015, we administered an online questionnaire to sites regarding facility characteristics and preparedness indicators. We estimated differences between members and nonmembers with natural logarithm-linked binomial models. Open-ended assessments identified preparedness gaps. RESULTS: One hundred seven sites completed the survey (23.3% response rate); 47 (43.9%) were nonmembers and 60 (56.1%) were members. Members were more likely to have completed hazard vulnerability analysis (risk ratio [RR] = 1.94; 95% confidence interval [CI] = 1.28, 2.93), to have identified essential services for continuity of operations (RR = 1.39; 95% CI = 1.03, 1.86), to have memoranda of understanding with external partners (RR = 2.49; 95% CI = 1.42, 4.36), and to have completed point-of-dispensing training (RR = 4.23; 95% CI = 1.76, 10.14). Identified preparedness gaps were improved communication, resource availability, and train-the-trainer programs. Public Health Implications. Primary Care Emergency Preparedness Network membership is associated with improved public health emergency preparedness among primary care sites.

Safety and tolerability of levocetirizine dihydrochloride in infants and children with allergic rhinitis or chronic urticaria.

Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are common causes of substantial illness and disability in preschool children. Antihistamines are commonly used to treat preschool children with these conditions, but their use is based mostly on extrapolated efficacy from adult populations; it is thus important to characterize the safety of antihistamines in the pediatric population. This study was designed to assess the safety of levocetirizine dihydrochloride oral liquid drops in infants and children with AR or CIU. Two multicenter, double-blind, randomized, parallel-group studies randomized infants aged 6-11 months (study 1, n = 69) and children aged 1-5 years (study 2, n = 173) to levocetirizine, 1.25 mg (q.d. or b.i.d., respectively), or placebo for 2 weeks, using a 2:1 ratio. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, electrocardiographic (ECG) assessments, and laboratory tests. The overall incidence of TEAEs was similar between levocetirizine and placebo in both studies. Most TEAEs were mild or moderate in intensity. TEAEs prompted discontinuation of therapy in three patients receiving levocetirizine in study 1. No clinically relevant changes from baseline in vital signs or laboratory parameters were apparent in either study; changes from baseline in these evaluations were similar between groups. No significant changes were observed in ECG parameters, including corrected QT interval. Levocetirizine, 1.25 and 2.5 mg/day, was well tolerated in infants aged 6-11 months and in children aged 1-5 years, respectively, with AR or CIU.

Efficacy and safety of levocetirizine in improving symptoms and health-related quality of life in US adults with seasonal allergic rhinitis: a randomized, placebo-controlled study.

BACKGROUND: Levocetirizine, a second-generation antihistamine for symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria, has not been previously studied in US patients. OBJECTIVE: To assess the efficacy and safety of levocetirizine in improving symptoms and health-related quality of life in US adults with seasonal allergic rhinitis (SAR). METHODS: This multicenter, double-blind trial randomized adults with SAR, sensitized to at least 1 grass allergen, to receive levocetirizine, 5 mg, or placebo once daily in the evening for 2 weeks. The primary end point was the 24-hour reflective Total 5-Symptom Score (T5SS; sum of rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) during the entire treatment period. Secondary assessments included the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS), each assessed at week 1, week 2, and the end of treatment. RESULTS: The intent-to-treat population comprised 287 patients taking levocetirizine and 290 taking placebo, with no significant between-group differences at baseline. Levocetirizine resulted in significantly greater improvement from baseline vs placebo in the T5SS (P < .001), overall RQLQ score (P < .001), general and work-related WPAI-AS subscores (P < .05), and ESS score (P < .001). Overall incidence of treatment-emergent adverse events was 14.4% for levocetirizine and 18.4% for placebo. The incidence of somnolence and fatigue was 0.7% and 1.8% with levocetirizine and 1.0% and 0% with placebo, respectively. CONCLUSIONS: Levocetirizine was well tolerated and was significantly more effective than placebo in improving the naso-ocular symptoms and health-related quality of life in US patients with SAR.

Study of levocetirizine in seasonal allergic rhinitis.

OBJECTIVE: To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults. RESEARCH DESIGN AND METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days. ClinicalTrials.gov registry no.: NCT00621959. MAIN OUTCOME MEASURES: Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs). RESULTS: The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 +/- 0.19; placebo, 9.04 +/- 0.19; adjusted mean difference, -0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified. CONCLUSIONS: In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality.

Change in formulation and its potential clinical and pharmacoeconomic value: example of extended release venlafaxine.

INTRODUCTION: The 505(b)(2) route of a New Drug Application (NDA) allows published literature or previous FDA findings of safety and effectiveness to be used for approval. Such drugs are not therapeutic equivalents (i.e., generics); instead, the FDA calls them pharmaceutical alternatives. A recent example is the approval of venlafaxine extended-release (ER) tablets, developed as an alternative to the widely used ER venlafaxine capsules. The smaller size of the tablets makes them available in a 225-mg strength, which is the approved maximum dose in major depressive disorder after up-titration but currently unavailable in the capsule formulation, requiring patients on this dose to take two or three capsules; in addition, the tablets are priced at a discount compared to the capsules. METHODS: The objective of this review was to investigate how the change in formulation of ER venlafaxine from capsules to tablets, as an example of such a change in formulation, can potentially offer value to patients and society, with a specific focus on pill burden, drug cost, and adherence. Based on a MEDLINE literature search, the pertinent literature was reviewed in a qualitative manner. REVIEW OF THE LITERATURE: Simplifying treatment regimens, reducing pill burden, and reducing drug costs are recognized strategies for improving adherence. This can be of particular benefit in psychiatric illness because of high rates of nonadherence to treatment. Lack of adherence may negatively impact treatment outcomes and increase disease cost. As such, the ER venlafaxine tablets have the potential to reduce pill burden, improve adherence and outcomes, and reduce cost to patients and society. These preliminary findings need to be corroborated with more primary research and a systematic review of formulation changes. CONCLUSION: A change in formulation of established therapies such as ER venlafaxine has the potential to offer clinical and pharmacoeconomic benefits to patients and society.

Bioequivalence of single and multiple doses of venlafaxine extended-release tablets and capsules in the fasted and fed states: four open-label, randomized crossover trials in healthy volunteers.

BACKGROUND: Venlafaxine extended-release (ER) tablets use osmotic pressure to deliver venlafaxine hydrochloride at a controlled rate over approximately 24 hours. OBJECTIVE: These studies were conducted to evaluate the bioequivalence of venlafaxine ER tablets and capsules based on the US Food and Drug Administration (FDA) definition. METHODS: Four pharmacokinetic studies of the capsule (reference) and tablet (test) formulations were conducted in healthy adult volunteers. The first 2 were randomized, single-dose, 4-way crossover studies of either a 37.5-mg dose (study A) or a 75-mg dose (study B) of the reference and test products under fasting and fed conditions. The other 2 were randomized, 2-way crossover studies of either a single dose (study C) or multiple doses (study D) of venlafaxine ER 225 mg, delivered as one venlafaxine ER 225-mg tablet or one 150-mg + one 75-mg venlafaxine ER capsules under fed conditions. The primary outcome measures were the log-transformed C(max), AUC(0-t), and AUC(0-infinity). If the 90% CIs for the ratios of the least squares means of the primary outcome measures between the reference and test formulations fell within the regulatory range (80%-125%), the 2 formulations would be considered bioequivalent according to the FDA definition. RESULTS: Thirty-six subjects (21 men, 15 women; mean [SD] age, 28.0 [8.7] years; mean weight, 161.0 [26.0] lb) were enrolled in study A and completed all treatment periods. Thirty-six subjects were enrolled in study B, of whom 30 (22 men, 8 women; mean age, 33.5 [9.6] years; mean weight, 172.7 [23.9] lb) completed all treatment periods. Thirty-six subjects were enrolled in study C, of whom 28 (16 men, 12 women; mean age, 33.1 [12.9] years; mean weight, 160.6 [29.6] lb) completed the study. Thirty-four subjects were enrolled in study D, of whom 33 (29 men, 4 women; mean age, 26.0 [8.1] years; mean weight, 178.0 [30.3] lb) completed the study. In study A, the 90% CIs for the log-transformed ratio (test vs reference) of C(max), AUC(0-t), and AUC(0-infinity) in the fasted state were 95.58 to 107.48, 97.58 to 111.09, and 100.31 to 112.85, respectively; in the fed state, the corresponding values were 84.26 to 94.86, 93.49 to 106.58, and 98.98 to 111.91. In study B, the respective values in the fasted state were 113.07 to 126.10, 111.11 to 124.57, and 106.86 and 120.71; in the fed state, the values were 90.50 to 100.90, 96.80 to 108.50, and 95.05 to 107.21. In study C, fed values were 94.15 to 109.37, 103.8 to 115.85, and 102.64 to 113.39. In study D, which involved multiple doses, fed values for C(max) and AUC(0-t) were 82.26 to 88.77 and 101.16 to 109.45, respectively. Adverse effects included nausea, vomiting, dizziness, syncope, and somnolence. CONCLUSIONS: In these single- and multiple-dose studies, all doses of venlafaxine ER tablets tested met the FDA criterion for bioequivalence to the equivalent doses of venlafaxine ER capsules in the fed state. In the fasted state, the bioequivalence criterion was met for venlafaxine ER 37.5-mg tablets but not venlafaxine 75-mg tablets.

Pilot study on the comprehensive economic costs of major trauma: Consequential costs are well in excess of medical costs.

BACKGROUND: Trauma care is expensive. However, reliable data on the exact lifelong costs incurred by a major trauma patient are lacking. Discussion usually focuses on direct medical costs--underestimating consequential costs resulting from absence from work and permanent disability. METHODS: Direct medical costs and consequential costs of 63 major trauma survivors (ISS >13) at a Swiss trauma center from 1995 to 1996 were assessed 5 years posttrauma. The following cost evaluation methods were used: correction cost method (direct cost of restoring an original state), human capital method (indirect cost of lost productivity), contingent valuation method (human cost as the lost quality of life), and macroeconomic estimates. RESULTS: Mean ISS (Injury Severity Score) was 26.8 +/- 9.5 (mean +/- SD). In all, 22 patients (35%) were disabled, causing discounted average lifelong total costs of USD 1,293,800, compared with 41 patients (65%) who recovered without any disabilities with incurred costs of USD 147,200 (average of both groups USD 547,800). Two thirds of these costs were attributable to a loss of production whereas only one third was a result of the cost of correction. Primary hospital treatment (USD 27,800 +/- 37,800) was only a minor fraction of the total cost--less than the estimated cost of police and the judiciary. Loss of quality of life led to considerable intangible human costs similar to real costs. CONCLUSIONS: Trauma costs are commonly underestimated. Direct medical costs make up only a small part of the total costs. Consequential costs, such as lost productivity, are well in excess of the usual medical costs. Mere cost averages give a false estimate of the costs incurred by patients with/without disabilities.