Real-world Effectiveness of Azacitidine in Treatment-Naive Patients With Higher-risk Myelodysplastic Syndromes.

INTRODUCTION: Azacitidine (AZA) is an approved frontline therapy for higher-risk myelodysplastic syndromes (HR-MDS); however, poor survival denotes unmet needs to increase depth/duration of response (DOR). METHODS: This retrospective study with patient chart review evaluated AZA effectiveness in 382 treatment-naive patients with HR-MDS from a US electronic health record (EHR)-derived database. Responses were assessed using International Working Group (IWG) 2006 criteria; real-world equivalents were derived from EHRs. Primary endpoint was IWG 2006-based complete remission rate (CRR). Secondary endpoints were EHR-based CRR, IWG 2006- and EHR-based objective response rates (ORRs), duration of CR, DOR, progression-free survival, time-to-next-treatment, and overall survival (OS). RESULTS: Using IWG 2006 criteria, the CRR was 7.9% (n = 30); median duration of CR was 12.0 months (95% CI, 7.7-15.6). In poor cytogenetic risk (n = 101) and TP53 mutation (n = 46) subgroups, CRRs were 7.9% (n = 8) and 8.7% (n = 4), respectively. ORR was 62.8% (n = 240), including a hematologic improvement rate (HIR) of 46.9% (n = 179). Using EHR-based data, CRR was 3.7% (n = 14); median duration of CR was 13.5 months (95% CI, 4.5-21.5). ORR was 67.8% (n = 259), including an HIR of 29.3% (n = 112). Median follow-up was 12.9 months; median OS was 17.9 months (95% CI, 15.5-21.7). CONCLUSIONS: Consistent with other studies, CRRs and median OS with AZA in treatment-naive patients with HR-MDS were low in this large, real-world cohort. Novel agents/combinations are urgently needed to improve these outcomes in HR-MDS.

Clinical Pharmacology Applications of Real-World Data and Real-World Evidence in Drug Development and Approval-An Industry Perspective.

Since the 21st Century Cures Act was signed into law in 2016, real-world data (RWD) and real-world evidence (RWE) have attracted great interest from the healthcare ecosystem globally. The potential and capability of RWD/RWE to inform regulatory decisions and clinical drug development have been extensively reviewed and discussed in the literature. However, a comprehensive review of current applications of RWD/RWE in clinical pharmacology, particularly from an industry perspective, is needed to inspire new insights and identify potential future opportunities for clinical pharmacologists to utilize RWD/RWE to address key drug development questions. In this paper, we review the RWD/RWE applications relevant to clinical pharmacology based on recent publications from member companies in the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) RWD Working Group, and discuss the future direction of RWE utilization from a clinical pharmacology perspective. A comprehensive review of RWD/RWE use cases is provided and discussed in the following categories of application: drug-drug interaction assessments, dose recommendation for patients with organ impairment, pediatric plan development and study design, model-informed drug development (e.g., disease progression modeling), prognostic and predictive biomarkers/factors identification, regulatory decisions support (e.g., label expansion), and synthetic/external control generation for rare diseases. Additionally, we describe and discuss common sources of RWD to help guide appropriate data selection to address questions pertaining to clinical pharmacology in drug development and regulatory decision making.

Clinical characteristics and overall survival among acute myeloid leukemia patients with TP53 gene mutation or chromosome 17p deletion.

Approximately 5% to 15% of acute myeloid leukemia (AML) patients have TP53 gene mutations (TP53m), which are associated with very poor outcomes. Adults (≥18 years) with a new AML diagnosis were included from a nationwide, de-identified, real-world database. Patients receiving first-line therapy were divided into three cohorts: venetoclax (VEN) + hypomethylating agents (HMAs; Cohort A), intensive chemotherapy (Cohort B), or HMA without VEN (Cohort C). A total of 370 newly diagnosed AML patients with TP53m (n = 124), chromosome 17p deletion (n = 166), or both (n = 80) were included. The median age was 72 years (range, 24-84); most were male (59%) and White (69%). Baseline bone marrow (BM) blasts were ≤30%, 31%-50%, and >50% in 41%, 24%, and 29% of patients in Cohorts A, B, and C, respectively. BM remission (<5% blasts) with first-line therapy was reported in 54% of patients (115/215) overall, and 67% (38/57), 62% (68/110), and 19% (9/48) for respective cohorts (median BM remission duration: 6.3, 6.9, and 5.4 months). Median overall survival (95% CI) was 7.4 months (6.0-8.8) for Cohort A, 9.4 months (7.2-10.4) for Cohort B, and 5.9 months (4.3-7.5) for Cohort C. There were no differences in survival by treatment type after adjusting for the effects of relevant covariates (Cohort A vs. C adjusted hazard ratio [aHR] = 0.9; 95% CI, 0.7-1.3; Cohort A vs. B aHR = 1.0; 95% CI, 0.7-1.5; and Cohort C vs. B aHR = 1.1; 95% CI, 0.8-1.6). Patients with TP53m AML have dismal outcomes with current therapies, demonstrating the high unmet need for improved treatments.

Treatment outcomes for newly diagnosed, treatment-naïve TP53-mutated acute myeloid leukemia: a systematic review and meta-analysis.

BACKGROUND: TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA). METHODS: We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), duration of response (DoR), and overall response rate (ORR) among patients with TP53m AML receiving first-line treatment with IC, HMA, or VEN + HMA. RESULTS: Searches of EMBASE and MEDLINE identified 3006 abstracts, and 17 publications describing 12 studies met the inclusion criteria. Random-effects models were used to pool response rates, and time-related outcomes were analyzed with the median of medians method. IC was associated with the greatest CR rate of 43%, and CR rates were 33% for VEN + HMA and 13% for HMA. Rates of CR/CRi were comparable for IC (46%) and VEN + HMA (49%) but were lower for HMA (13%). Median OS was uniformly poor across treatments: IC, 6.5 months; VEN + HMA, 6.2 months; and HMA, 6.1 months. For IC, the EFS estimate was 3.7 months; EFS was not reported for VEN + HMA or HMA. The ORR was 41% for IC, 65% for VEN + HMA, and 47% for HMA. DoR was 3.5 months for IC, 5.0 months for VEN + HMA, and was not reported for HMA. CONCLUSIONS: Despite improved responses seen with IC and VEN + HMA compared to HMA, survival was uniformly poor, and clinical benefits were limited across all treatments for patients with newly diagnosed, treatment-naïve TP53m AML, demonstrating a significant need for improved treatment for this difficult-to-treat population.

Azacitidine Monotherapy in Patients With Treatment-Naïve Higher-risk Myelodysplastic Syndrome: A Systematic Literature Review and Meta-analysis.

BACKGROUND: The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes. MATERIALS AND METHODS: We assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for patients treated with AZA monotherapy. Noncomparative meta-analyses were used to summarize effects. RESULTS: The search identified 3250 abstracts, of which 34 publications describing 16 studies (5 RCTs, 3 prospective, and 8 retrospective observational) were included. Across all studies, pooled CR was 16%; PR was 6%; Median OS was 16.4 months; median DOR was 10.1 months; median TTR was 4.6 months. Proportions of grade 3/4 anemia and thrombocytopenia AEs were 10% and 30%. CONCLUSIONS: The effectiveness and efficacy of AZA monotherapy-as measured by CR and median OS-was limited. These findings highlight a significant unmet medical need for effective treatments for patients with higher-risk MDS.

Integrating real-world data to accelerate and guide drug development: A clinical pharmacology perspective.

Pharmaceutical products in the current accelerated drug development landscape can benefit from tools beyond data generated from randomized control trials. We have seen an abundance of real-world data (RWD) and real-world evidence, driven by the digitalization of healthcare systems and an increased awareness that has inspired a heightened interest in their potential use. Literature review suggest leveraging RWD as a promising tool to answer key questions in the areas of clinical pharmacology and translational science. RWD may increase our understanding regarding the impact of intrinsic (e.g., liver, renal impairment, or genetic polymorphisms) and extrinsic (e.g., food consumption or concomitant medications) factors on the clearance of administered drugs. Changes in clearance may lead to clinically relevant changes in drug exposure that may require clinical management strategies, such as change in dose or dosing regimen. RWD can be leveraged to potentially bridge the gaps among research, development, and clinical care. This paper highlights promising areas of how RWD have been used to complement clinical pharmacology throughout various phases of drug development; case examples will include dose/regimen extrapolation, dose adjustments for special populations (organ impairment, pediatrics, etc.), and pharmacokinetic/pharmacodynamic models to assess impact of prognostic factors on outcomes. In addition, this paper will also juxtapose limitations and promises of utilizing RWD to answer key scientific questions in drug development and articulate challenges posed by quality issues, data availability, and integration from various sources as well as the increased need for multidimensional-omics data that can better guide the development of personalized and predictive medicine.

A Retrospective Study of Comorbidities and Complications in Elderly Acute Myeloid Leukemia Patients in the United States.

BACKGROUND: Comorbidities in acute myeloid leukemia (AML) patients have been shown to increase with age. However, few studies have described the disease burden in elderly AML patients, a population generally underrepresented in clinical trials. We aimed to characterize the comorbidities and complications in elderly AML patients. PATIENTS AND METHODS: Patients aged ≥ 65 years with a primary diagnosis of AML were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (2000-2013) and were followed until the end of 2014. AML patients were matched 1:1 to noncancer patients by age, sex, geographic region, and race. A subset of patients with relapsed and/or refractory (R/R) AML was identified by modifying a previously validated algorithm. Baseline comorbidities and complications (eg, infectious, hematologic, cardiovascular) during follow-up were assessed using ICD-9 codes. Cox proportional hazards models were used to determine associations between AML and developing select complications. RESULTS: Compared to matched noncancer controls, AML patients (n = 3911) had higher baseline National Cancer Institute comorbidity index scores (1.81 vs. 1.63, P < .01), higher incidence rates (per 100 person-years) for all events of interest, and a higher risk of developing cardiovascular disease (hazard ratio = 4.61; 95% confidence interval, 4.07-5.21), type 2 diabetes mellitus (hazard ratio = 3.85; 95% confidence interval, 3.35-4.42), and stroke (hazard ratio = 2.60; 95% confidence interval, 2.32-2.92). R/R AML patients were younger, had lower National Cancer Institute comorbidity scores, lower incidence rates of events of interest, and a longer follow-up time compared to non-R/R AML patients. CONCLUSION: Elderly AML patients had more comorbidities and higher rates of complications compared to noncancer controls. Considering comorbidities and complications in elderly AML patients may improve clinical decision making.

Assessing Fever Frequency After Pediatric Live Attenuated Versus Inactivated Influenza Vaccination.

BACKGROUND: Some studies have found a higher frequency of fever with trivalent live attenuated influenza vaccine (LAIV) than with inactivated influenza vaccine (IIV), but quadrivalent LAIV has not been assessed. Understanding fever is important for safety reviews and for parents and providers. In addition, there have been only a limited number of studies in which text messaging was used for vaccine adverse-event (AE) surveillance. METHODS: We conducted a prospective observational study in 3 community clinics in New York City to assess post-influenza vaccination fever in 24- to 59-month-olds during the 2013-2014 season. Enrolled families of children who received quadrivalent LAIV (LAIV4) or IIV (trivalent IIV3 or quadrivalent IIV4) replied to text messages that assessed their temperature on vaccination night and the next 10 nights (days 0 to 10); missing data were collected via telephone and a diary. We compared frequencies of fever (temperature ≥ 100.4°F) according to vaccine group on days 0 to 2 and 3 to 10 by using χ2 and multivariate log-binomial regression adjusted for age, previous influenza vaccination, and vaccine coadministration. We also assessed outcomes using all sources versus only text messages. RESULTS: Most (84.1% [n = 540]) eligible parents enrolled. Fever frequencies on days 0 to 2 did not differ between LAIV4 and any IIV (3.8% vs 5.7%, respectively; adjusted relative risk [aRR] [95% confidence interval], 0.60 [0.25-1.46]), between LAIV4 and IIV4 (4.2% vs 7.1%, respectively; aRR, 0.58 [0.19-1.72]), or between IIV4 and IIV3 (7.1% vs 6.0%, respectively; aRR, 1.02 [0.30-3.46]). The findings were similar when all data sources versus text-message data alone were used. There were no significant differences on days 3 to 10. CONCLUSIONS: Postvaccination fever frequencies were low overall and did not differ according to influenza vaccine type during the 2013-2014 influenza season. The similarity of results when data were limited to text messages lends support to its use for surveillance of vaccine adverse events.

Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000-12.

BACKGROUND: Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS). METHODS: We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV). FINDINGS: Of the 41,792 adverse event reports submitted, 39,568 (95%) were for children younger than 7 years. 38,381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34,880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most commonly coded term for non-serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths (96%) were in children aged 12 months or younger; most (52%) had sudden infant death syndrome as the reported cause of death. The safely profiles of combined IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and OPV and acellular pertussis vaccines were similar. We noted no indication of disproportionate reporting of adverse events after immunisation with IPV-containing vaccines compared with other vaccines between 1990 and 2013. INTERPRETATION: Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV. FUNDING: None.

Relationship between Guillain-Barré syndrome, influenza-related hospitalizations, and influenza vaccine coverage.

Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (P&I) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and P&I temporal clusters were identified using scan statistics. The association between P&I and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly P&I and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p<0.0001). A significant (p=0.001) cluster of P&I hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, P&I hospitalization was significantly associated (p<0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the month of June. P&I hospitalization rates were significantly correlated with hospitalization rates for GBS. Vaccine coverage did not significantly affect the rates of GBS hospitalization at the population level.

Updated recommendations for the use of typhoid vaccine--Advisory Committee on Immunization Practices, United States, 2015.

These revised recommendations of the Advisory Committee on Immunization Practices update recommendations published in MMWR in 1994 and include updated information on the two currently available vaccines and on vaccine safety. They also include an update on the epidemiology of enteric fever in the United States, focusing on increasing drug resistance in Salmonella enterica serotype Typhi, the cause of typhoid fever, as well as the emergence of Salmonella serotype Paratyphi A, a cause of paratyphoid fever, against which typhoid vaccines offer little or no protection.

Using the exhibited generalization approach to evaluate a carbon monoxide alarm ordinance.

Current interests in enhancing the focus of external validity or transferability call for developing practical evaluation approaches and illustrating their applications in this area for meeting the need. This study takes the challenge by introducing an innovative evaluation approach, named the exhibited generalization approach, and applying it in evaluating the carbon monoxide (CO) alarm ordinance passed by Mecklenburg County, North Carolina. The stakeholders specifically asked evaluators to determine the answers to the following two questions: (1) Does the alarm ordinance work? (2) What generalizable information can the Mecklenburg experience provide to other jurisdictions trying to decide if the alarm ordinance's planning, implementation, adoption, and outcomes are transferable to their communities? This study illustrates how to apply the exhibited generalization approach to provide the stakeholders with answers to these questions. Our results indicate that the alarm ordinance was effective in increasing CO alarm ownerships and reducing CO poisoning cases. The evaluation provides potential users and other interested parties with the necessary information on contextual factors and the causal mechanism underlying the CO alarm ordinance, so that these parties and users could decide whether the Mecklenburg alarm ordinance would be transferable to their own communities. Discussions include implications of this study for contributing in further advancing evaluation theory in addressing transferability or external validity issues.

Cumulative risk of Guillain-Barré syndrome among vaccinated and unvaccinated populations during the 2009 H1N1 influenza pandemic.

OBJECTIVES: We sought to assess risk of Guillain-Barré syndrome (GBS) among influenza A (H1N1) 2009 monovalent (pH1N1) vaccinated and unvaccinated populations at the end of the 2009 pandemic. METHODS: We applied GBS surveillance data from a US population catchment area of 45 million from October 15, 2009, through May 31, 2010. GBS cases meeting Brighton Collaboration criteria were included. We calculated the incidence density ratio (IDR) among pH1N1 vaccinated and unvaccinated populations. We also estimated cumulative GBS risk using life table analysis. Additionally, we used vaccine coverage data and census population estimates to calculate denominators. RESULTS: There were 392 GBS cases; 64 (16%) occurred after pH1N1vaccination. The vaccinated population had lower average risk (IDR = 0.83, 95% confidence interval = 0.63, 1.08) and lower cumulative risk (6.6 vs 9.2 cases per million persons, P = .012) of GBS. CONCLUSIONS: Our findings suggest that at the end of the influenza season cumulative GBS risk was less among the pH1N1vaccinated than the unvaccinated population, suggesting the benefit of vaccination as it relates to GBS. The observed potential protective effect on GBS attributed to vaccination warrants further study.

Guillain-Barre syndrome, influenza, and influenza vaccination: the epidemiologic evidence.

Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis worldwide, and is thought to be immune-mediated. It is preceded by upper respiratory or gastrointestinal infection in about two-thirds of cases and is associated with some viral infections, including influenza. GBS has also been associated with the 1976 swine-influenza vaccine. Thereafter, some studies have shown a small increased risk of GBS following receipt of seasonal and 2009 H1N1 monovalent influenza vaccines. Studies over the years have also shown an increased risk of GBS following influenza infection, and the magnitude of risk is several times greater than that following influenza vaccination. Because GBS is rare, and even rarer following vaccination, it is difficult to estimate precise risk. We try to shed light on the complex relationship of GBS and its association with influenza and influenza vaccines over the past 35 years.

Association between birthplace and current asthma: the role of environment and acculturation.

OBJECTIVES: We evaluated associations between current asthma and birthplace among major racial/ethnic groups in the United States. METHODS: We used multivariate logistic regression methods to analyze data on 102,524 children and adolescents and 255,156 adults in the National Health Interview Survey (2001-2009). RESULTS: We found significantly higher prevalence (P < .05) of current asthma among children and adolescents (9.3% vs 5.1%) and adults (7.6% vs 4.7%) born in the 50 states and Washington, DC (US-born), than among those born elsewhere. These differences were among all age groups of non-Hispanic Whites, non-Hispanic Blacks, and Hispanics (excluding Puerto Ricans) and among Chinese adults. Non-US-born adults with 10 or more years of residency in the United States had higher odds of current asthma (odds ratio = 1.55; 95% confidence interval = 1.25, 1.93) than did those who arrived more recently. Findings suggested a similar trend among non-US-born children. CONCLUSIONS: Current asthma status was positively associated with being born in the United States and with duration of residency in the United States. Among other contributing factors, changes in environment and acculturation may explain some of the differences in asthma prevalence.

Number of antigens in early childhood vaccines and neuropsychological outcomes at age 7-10 years.

PURPOSE: Concerns have been raised that children may be receiving too many immunizations under the recommended schedule in the USA. We used a publicly available dataset to evaluate the association between antibody-stimulating proteins and polysaccharides from early childhood vaccines and neuropsychological outcomes at age 7-10 years. METHODS: Children aged 7-10 years from four managed care organizations underwent standardized tests for domain-specific neuropsychological outcomes: general intellectual function, speech and language, verbal memory, attention and executive function, tics, achievement, visual spatial ability, and behavior regulation. Vaccination histories up to 24 months of age were obtained from medical charts, electronic records, and parents' records. Logistic regressions and structural equation modeling (SEM) were used to determine associations between total antigens up to 7, 12, and 24 months and domain-specific outcomes. RESULTS: On average, children (N = 1047) received 7266, 8127, and 10 341 antigens by ages 7, 12, and 24 months, respectively. For adjusted analyses, increase (per 1000) in the number of antigens was not associated with any neuropsychological outcomes. Antigen counts above the 10th percentile, compared with lower counts, were also not associated with any adverse outcomes. However, children with higher antigen counts up to 24 months performed better on attention and executive function tests (odds ratio for lower scores = 0.51, 95% confidence interval = 0.26, 0.99). Similar results were found with SEM analysis (b = 0.08, p = 0.02). CONCLUSIONS: We did not find any adverse associations between antigens received through vaccines in the first two years of life and neuropsychological outcomes in later childhood. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Racial and ethnic disparities in current asthma and emergency department visits: findings from the National Health Interview Survey, 2001-2010.

OBJECTIVES: Racial/ethnic disparities in current asthma prevalence and medical care are a major public health concern. We examined the differences in asthma prevalence and morbidity among major racial/ethnic populations in the US. METHODS: We analyzed data from the 2001-2010 National Health Interview Survey for adults (≥18 years) and children and adolescents (<18 years). Outcome variables were current asthma prevalence, at least one attack in the past 12 months, and at least one asthma-related emergency department/urgent care center (ED/UCC) visit in the past 12 months. We used multivariate logistic regression to calculate the model-adjusted prevalence and risk ratios (ARR). RESULTS: In our study, 9.0% of the children and 7.2% of the adults had current asthma. Non-Hispanic black and Puerto Rican children were more likely to have current asthma (ARR 1.46, 1.66, respectively) and to visit the ED/UCC (ARR 1.61, 1.67, respectively) than non-Hispanic whites. American Indian/Alaskan Native children were more likely to have current asthma (ARR 1.76) than non-Hispanic whites. Mexican/Mexican American children and adults had lower prevalence of current asthma but higher ED/UCC use (adults only) than non-Hispanic whites. Among adults, Puerto Ricans and American Indian/Alaskan Natives were more likely to have current asthma (ARR 1.60, 1.39, respectively) than non-Hispanic whites, and all the studied racial/ethnic groups except Asians were more likely to have visited the ED/UCC than non-Hispanic whites. Adults and children who received emergency care for asthma in the past 12 months more frequently received multiple components of asthma management and control (e.g., taking long-term medication, having an asthma management plan) compared to those without emergency care. CONCLUSIONS: Racial/ethnic differences in current asthma prevalence, asthma attacks, and increased utilization of emergency room visits for asthma among minorities persist among children and adults. Appropriate and effective asthma management and education may lead to better asthma control and reduce emergency care utilization.

National carbon monoxide poisoning surveillance framework and recent estimates.

OBJECTIVES: Unintentional, non-fire-related (UNFR) carbon monoxide (CO) poisoning is a leading cause of poisoning in the United States. A comprehensive national CO poisoning surveillance framework is needed to obtain accurate estimates of CO poisoning burden and guide prevention efforts. This article describes the current national CO poisoning surveillance framework and reports the most recent national estimates. METHODS: We analyzed mortality data from the National Vital Statistics System multiple cause-of-death file, emergency department (ED) and hospitalization data from the Healthcare Cost and Utilization Project's Nationwide Emergency Department Sample and Nationwide Inpatient Sample, hyperbaric oxygen treatment (HBOT) data from HBOT facilities, exposure data from the National Poison Data System, and CO alarm prevalence data from the American Housing Survey and the National Health Interview Survey. RESULTS: In the United States, 2,631 UNFR CO deaths occurred from 1999 to 2004, an average of 439 deaths annually. In 2007, there were 21,304 (71 per one million population) ED visits and 2,302 (eight per one million population) hospitalizations for confirmed cases of CO poisoning. In 2009, 552 patients received HBOT, and from 2000 to 2009, 68,316 UNFR CO exposures were reported to poison centers. Most nonfatal poisonings were among children (<18 years of age) and females; hospitalizations and deaths occurred more frequently among males and elderly people (>65 years of age). More poisonings occurred during winter months and in the Midwest and Northeast. CONCLUSIONS: UNFR CO poisoning poses a significant public health burden. Systematic evaluation of data sources coupled with modification and expansion of the surveillance framework might assist in developing effective prevention strategies.

A review of disaster-related carbon monoxide poisoning: surveillance, epidemiology, and opportunities for prevention.

OBJECTIVES: We conducted a systematic literature review to better understand aspects of disaster-related carbon monoxide (CO) poisoning surveillance and determine potentially effective prevention strategies. METHODS: This review included information from 28 journal articles on disaster-related CO poisoning cases occurring between 1991 and 2009 in the United States. RESULTS: We identified 362 incidents and 1888 disaster-related CO poisoning cases, including 75 fatalities. Fatalities occurred primarily among persons who were aged 18 years or older (88%) and male (79%). Hispanics and Asians accounted for 20% and 14% of fatal cases and 21% and 7% of nonfatal cases, respectively. Generators were the primary exposure source for 83% of fatal and 54% of nonfatal cases; 67% of these fatal cases were caused by indoor generator placement. Charcoal grills were a major source of exposure during winter storms. Most fatalities (94%) occurred at home. Nearly 89% of fatal and 53% of nonfatal cases occurred within 3 days of disaster onset. CONCLUSIONS: Public health prevention efforts could benefit from emphasizing predisaster risk communication and tailoring interventions for racial, ethnic, and linguistic minorities. These findings highlight the need for surveillance and CO-related information as components of disaster preparedness, response, and prevention.

Residential carbon monoxide alarm prevalence and ordinance awareness.

OBJECTIVE: Unintentional carbon monoxide (CO) poisoning is a leading cause of poisoning in the United States. Most poisoning cases occur in residential settings and a working CO alarm may prevent many of these events. The use of a CO alarm is mandated in many parts of the country; however, little is known about the compliance and adoption of such ordinances at the population level. This study determined the prevalence of residential CO alarm and awareness of a 2001 CO alarm ordinance in Mecklenburg County, North Carolina in 2009. METHODS: A random sample of households stratified by housing type (eg, single-family homes, multifamily homes) was included in a cross-sectional survey conducted. One adult respondent from each household was administered a questionnaire that included information on sociodemographic and household characteristics, presence of a CO alarm, and CO alarm ordinance awareness. Data were analyzed using multivariate stratified conditional logistic regression. RESULTS: Among 214 participating households (response rate, 23.4%), 145 (67.8%) reported having a working CO alarm and 79 (36.9%) of the respondents were aware of the CO alarm ordinance. Respondents who were aware of the ordinance had 9 times higher odds (95% confidence interval, 3.3-25.9) of having a CO alarm than those who were unaware. Also, households with an attached garage had more than 2 times higher odds (95% confidence interval, 1.0-6.2) of having a CO alarm than those without an attached garage. Awareness of the CO alarm ordinance was not associated with any sociodemographic (eg, age, sex, race, education, income) or household (eg, home ownership, home construction year) characteristics. CONCLUSIONS: Carbon monoxide alarm prevalence in Mecklenburg County households was higher than the national average and was associated with CO alarm ordinance awareness. Public health efforts might benefit from regulations aimed at population-level adoption of preventive health behaviors.