Trends in Sickle Cell Disease-Related Mortality in the United States, 1979 to 2017.

STUDY OBJECTIVE: We provide an updated assessment of trends in sickle cell disease (SCD)-related mortality, a significant source of mortality in the United States among black persons, using 1979 to 2017 US mortality data. METHODS: SCD-related deaths were identified with International Classification of Diseases codes. Because SCD-related death is rare in other races, the analysis focused on black decedents. Age-specific and average annual SCD-related death rates were calculated. Causes of death codes were categorized into 20 groups relevant to SCD outcomes. SCD-related deaths were compared with non-SCD-related deaths after matching on race, sex, age group, and year of death. RESULTS: There were 25,665 SCD-related deaths reported among blacks in the United States from 1979 through 2017. During that period, the annual SCD-related death rate declined in children and increased in adults, and the median age at death increased from 28 to 43 years. Acute causes of death, such as infection and cerebrovascular complications, were more common in younger age groups. Chronic complications were more common in adults. SCD-related deaths were more likely to be related to acute cardiac, pulmonary, and cerebrovascular complications; acute infections; and chronic cardiac and pulmonary complications and renal disorders; and less likely to be related to drug overdose and chronic infections than non-SCD-related deaths. CONCLUSION: These data indicate SCD-related deaths are now more likely to be related to chronic complications of the disease than to acute complications. More research regarding prevention and treatment of chronic complications of SCD is necessary because persons with SCD are living longer.

Estimation of Undiagnosed Naegleria fowleri Primary Amebic Meningoencephalitis, United States1.

Primary amebic meningoencephalitis is an acute, rare, typically fatal disease. We used epidemiologic risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit the typical pattern for primary amebic meningoencephalitis; we estimated an annual average of 16 deaths (8 male, 8 female) in the United States.

Infant and maternal risk factors related to necrotising enterocolitis-associated infant death in the United States.

AIM: To evaluate necrotising enterocolitis (NEC)-associated infant death and identify risk factors related to NEC infant death in the United States. METHODS: The United States Period Linked Birth/Infant Death data for 2010-2013 were utilised to determine risk factors associated with NEC infant death. Infant mortality rates (IMRs) were calculated and a retrospective matched case-control analysis was performed. An infant case was defined as having the International Classification of Diseases, Tenth Revision code for NEC listed on the death record. Controls were matched on birthweight and randomly selected. Conditional multivariable logistic regression models stratified by birthweight were conducted to determine risk factors for NEC infant death. RESULTS: The average annual NEC IMR was 12.5 deaths per 100 000 live births and was higher among very low birthweight (VLBW) compared to normal birthweight infants and among black compared to white infants. For VLBW infants, the multivariable analysis identified male sex, five-minute Apgar score of less than 7, and white infants born to a mother who is less than or equal to 19 years of age to be related with NEC-associated infant death. CONCLUSION: Paediatricians should be aware of the factors related to NEC-associated infant death to reduce the number of infants at greatest risk for NEC and focus on racial disparities.

Chronic Liver Disease-Associated Hospitalizations Among Adults with Diabetes, National Inpatient Sample, 2001-2012.

OBJECTIVE: Many people with diabetes have a variety of diabetes-related complications. Among the variety of conditions associated with diabetes, however, liver diseases are less well recognized. As such, we aimed to describe chronic liver disease (CLD)-associated hospitalization rates among U.S. adults with diabetes from 2001-2012. METHODS: We used a nationally representative database of hospitalizations, the National Inpatient Sample, to determine CLD-associated hospitalization rates among U.S. adults aged ≥ 18 years with and without diabetes, from 2001-2012. Hospitalizations listing an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for CLD on the discharge record were selected for analysis and were further classified by diabetes status based on concurrent presence of a diabetes ICD-9-CM code. We calculated average annual age-adjusted hospitalization rates and 95% confidence intervals (CIs), and conducted a test for trend. RESULTS: For 2001-2012, the total age-adjusted CLD-associated hospitalization rate among adults with diabetes (1,680.9 per 100,000 population; 95% CI 1,577.2, 1,784.6) was approximately four times the rate of adults without diabetes (424.2 per 100,000 population; 95% CI 413.4, 435.1). Total age-adjusted hospitalization rates of adults with and without diabetes increased 59% and 48%, respectively, from 2001-2002 to 2011-2012 (p<0.001). Hepatitis C- and chronic hepatitis and cirrhosis-associated hospitalizations comprised the largest proportion of total CLD-associated hospitalizations among adults with and without diabetes. CONCLUSION: Providers should be aware of the potential existence of CLD among adults with diabetes and counsel patients on preventive methods to avoid progressive liver damage.

Incidence and prevalence of Parkinson's disease among Navajo people living in the Navajo nation.

Parkinson's disease (PD) is largely unstudied among American Indians. Unique populations might harbor clues to elusive causes. We describe the incidence and prevalence of PD among Navajo people residing in the Navajo Nation, home to the largest American Indian tribe in the United States. We analyzed 2001-2011 inpatient and outpatient visit data for Navajo people obtained from the Indian Health Service, which provides health care to American Indian people living on the Navajo Reservation. Cases were defined by at least two inpatient or outpatient visits with the diagnosis of PD. Crude and age-adjusted incidence and prevalence rates were calculated overall as well as by age, sex, region of residence, and time period. Five hundred twenty-four Navajo people with median age-at-onset of 74.0 years were diagnosed with PD during the study period, yielding an average annual crude incidence rate of 22.5/100,000. Age-specific incidence was 232.0 for patients 65 years of age or older and 302.0 for 80 years of age or older. Age-adjusted incidence was 35.9 overall (238.1 for ≥65 years), was higher in men than in women (47.5 vs. 27.7; P<0.001), varied by region (P=0.03), and was similar between time periods (2002-2004 vs. 2009-2011). The age-adjusted point prevalence rate was 261.0. The rate of PD among Navajo People appears to be as high as or higher than rates reported in many other populations. Rates increased to the highest age group, consistent with population-based studies. Further investigation is warranted to examine risk factors for PD in this remote population.

Molluscum contagiosum in a pediatric American Indian population: incidence and risk factors.

BACKGROUND: Molluscum contagiosum virus (MCV) causes an innocuous yet persistent skin infection in immunocompetent individuals and is spread by contact with lesions. Studies point to atopic dermatitis (AD) as a risk factor for MCV infection; however, there are no longitudinal studies that have evaluated this hypothesis. METHODS: Outpatient visit data from fiscal years 2001-2009 for American Indian and Alaska Native (AI/AN) children were examined to describe the incidence of molluscum contagiosum (MC). We conducted a case-control study of patients <5 years old at an Indian Health Service (IHS) clinic to evaluate dermatological risk factors for infection. RESULTS: The incidence rate for MC in children <5 years old was highest in the West and East regions. MC cases were more likely to have a prior or co-occurring diagnosis of eczema, eczema or dermatitis, impetigo, and scabies (p<0.05) compared to controls; 51.4% of MC cases had a prior or co-occurring diagnosis of eczema or dermatitis. CONCLUSIONS: The present study is the first demonstration of an association between AD and MC using a case-control study design. It is unknown if the concurrent high incidence of eczema and MC is related, and this association deserves further investigation.

Trends in encephalitis-associated deaths in the United States, 1999-2008.

BACKGROUND: While encephalitis may be caused by numerous infectious, immune and toxic processes, the etiology often remains unknown. METHODS: We analyzed multiple cause-of-death mortality data during 1999-2008 for the USA, using the 10th revision of International Classification of Diseases codes for encephalitis, listed anywhere on the death record, including 'specified' and 'unspecified' encephalitis. Annual and average annual age-adjusted and age-specific death rates were calculated. RESULTS: For 1999-2008, 12,526 encephalitis-associated deaths were reported with 68.5% as unspecified encephalitis. The average annual age-adjusted encephalitis-associated death rate was 4.3 per 1 million persons, 1.3 for specified and 2.9 for unspecified encephalitis. Annual encephalitis-associated death rates had a significant downward trend (p < 0.01). The most common specified encephalitis deaths were herpesviral encephalitis (36.7%), Toxoplasma meningoencephalitis (27.8%) and Listeria meningitis/meningoencephaltis (6.8%). HIV was colisted with 15.0% of encephalitis-associated deaths, 58.4% of these with a specified code. CONCLUSION: Encephalitis-associated death rates decreased during 1999-2008, and herpesvirus was the most commonly identified infectious agent associated with encephalitis deaths. The high proportion of unspecified encephalitis deaths highlights the continued challenge of laboratory confirmation for causes of encephalitis and the importance of monitoring trends to assess the impact of new diagnostics and guide potential interventions.

Risk factors for infectious disease death among infants in the United States.

BACKGROUND: Infectious diseases (IDs) are an important cause of infant mortality in the United States. This study describes maternal and infant characteristics associated with infant ID deaths in the United States. METHODS: Infant deaths with an ID underlying cause of death occurring in the United States were examined using the 2008-2009 Period Linked Birth/Infant Death public use data files. Average annual ID infant mortality rates for singleton infants were calculated. A retrospective case-control study was conducted to determine infant and maternal risk factors for infant ID death among low (LBW) and normal (NBW) birth weight groups. Controls were defined as infants surviving to the end of their birth year. Risk factors for infant ID deaths were determined through multivariable logistic regression. RESULTS: An estimated 3843 infant ID deaths occurred in the United States during 2008-2009, an overall ID infant mortality rate of 47.5 deaths per 100,000 live births. The mortality rate for LBW and NBW infants were 514.8 and 15.5, respectively. Male sex, younger maternal age (<25 years), a live birth order of fourth or more and low 5-minute Apgar score were associated with increased ID death among LBW and NBW infants. Additionally, black maternal race was associated with increased ID death among LBW infants, and having an unmarried mother was associated with increased ID death among NBW infants. CONCLUSIONS: Awareness of associations with infant ID death should help in development of further strategic measures to reduce infant ID morbidity and mortality.

Epidemiology of asthma hospitalizations among American Indian and Alaska Native people and the general United States population.

BACKGROUND: Asthma, a common chronic disease among adults and children in the United States, results in nearly one-half million hospitalizations annually. There has been no evaluation of asthma hospitalizations for American Indian and Alaska Native (AI/AN) people since a previous study using data for 1988-2002. In this study, we describe the epidemiology and trends for asthma hospitalizations among AI/AN people and the general US population for 2003-2011. METHODS: Hospital discharge records with a first-listed diagnosis of asthma for 2003-2011 were examined for AI/AN people, using Indian Health Service (IHS) data, and for the general US population, using the Nationwide Inpatient Sample. Average annual crude and age-adjusted hospitalization rates were calculated. RESULTS: The average annual asthma hospitalization rates for AI/AN people and the general US population decreased from 2003-2005 to 2009-2011 (32% and 11% [SE, 3%], respectively). The average annual age-adjusted rate for 2009-2011 was lower for AI/AN people (7.6 per 10,000 population) compared with the general US population (13.2 per 10,000; 95% CI, 12.8-13.6). Age-specific AI/AN rates were highest among infants and children 1 to 4 years of age. IHS regional rates declined in all regions except Alaska. CONCLUSIONS: Asthma hospitalization rates are decreasing for AI/AN people and the general US population despite increasing prevalence rates. AI/AN people experienced a substantially lower age-adjusted asthma hospitalization rate compared with the general US population. Although the rates for AI/AN infants and children 1 to 4 years of age have declined substantially, they remain higher compared with other age groups. Improved disease management and awareness should help to further decrease asthma hospitalizations, particularly among young children.

Encephalitis-associated hospitalizations among American Indians and Alaska Natives.

Encephalitis produces considerable morbidity in the United States, but morbidity rates among American Indian/Alaska Native (AI/AN) people have not been described. Hospitalization records listing an encephalitis diagnosis were analyzed by using Indian Health Service direct/contract inpatient data. For 1998-2010, there were 436 encephalitis-associated hospitalizations among AI/AN people, an average annual age-adjusted hospitalization rate of 3.1/100,000 population. The rate for infants (11.9) was more than double that for any other age group. Death occurred for 4.1% of hospitalizations. Consistent with reports for the general U.S. population, the rate was high among infants and most (53.9%) hospitalizations were of unexplained etiology. The average annual rate during the study period appeared lower than for the general U.S. population, due particularly to lower rates in the elderly. Future community-based surveillance and mortality studies are needed to confirm these findings and examine reasons underlying the low rates of encephalitis in AI/AN people.

Burden of encephalitis-associated hospitalizations in the United States, 1998-2010.

OBJECTIVE: To estimate the burden of encephalitis-associated hospitalizations in the United States for 1998-2010. METHODS: Using the Nationwide Inpatient Sample, a nationally representative database of hospitalizations, estimated numbers and rates of encephalitis-associated hospitalizations for 1998-2010 were calculated. Etiology and outcome of encephalitis-associated hospitalizations were examined, as well as accompanying diagnoses listed along with encephalitis on the discharge records. Total hospital charges (in 2010 US dollars) were assessed. RESULTS: An estimated 263,352 (standard error: 3,017) encephalitis-associated hospitalizations occurred in the United States during 1998-2010, which corresponds to an average of 20,258 (standard error: 232) encephalitis-associated hospitalizations per year. A fatal outcome occurred in 5.8% (95% confidence interval [CI]: 5.6%-6.0%) of all encephalitis-associated hospitalizations and in 10.1% (95% CI: 9.2%-11.2%) and 17.1% (95% CI: 14.6%-20.0%) of encephalitis-associated hospitalizations in which a code for HIV or a tissue or organ transplant was listed, respectively. The proportion of encephalitis-associated hospitalizations in which an etiology for encephalitis was specified was 50.3% (95% CI: 49.6%-51.0%) and that for which the etiology was unspecified was 49.7% (95% CI: 49.0%-50.4%). Total charges for encephalitis-associated hospitalizations in 2010 were an estimated $2.0 billion. CONCLUSIONS: Encephalitis remains a major public health concern in the United States. Among the large number of encephalitis-associated hospitalizations for which an etiology is not reported may be novel infectious and noninfectious forms of encephalitis. Associated conditions such as HIV or transplantation increase the risk of a fatal outcome from an encephalitis-associated hospitalization and should be monitored.

Changes in knowledge of bat rabies and human exposure among United States cavers.

The purpose of the study was to evaluate changes in the knowledge of bat rabies and human exposure among United States cavers during the last decade. A survey was distributed among cavers who attended the National Speleological Society convention in 2000 and those who attended in 2010. In 2000 and 2010, 392 and 108 cavers, respectively, responded to the questionnaire. Eighty-five per cent of respondents in 2000 indicated a bat bite as a risk for rabies compared with all respondents in 2010 (P < 0.0001 controlling for age). The proportion of respondents indicating that they were advised to receive rabies pre-exposure prophylaxis (PreEP) because of caving increased (17% and 29%; P = 0.03 controlling for age). Among these, PreEP was received by 56% and 45%. Although recognition of the risk of rabies exposure from bats is important, the proportion of cavers acting on current recommendations regarding PreEP does not appear to have improved in the past decade.

Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).

Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 10(8) PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo-treated controls that survived infection. Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans.

Amyotrophic lateral sclerosis/motor neuron disease deaths in the United States, 1999-2009.

Our objective was to examine trends and epidemiology of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) associated deaths in the United States. ALS/MND associated death rates and trends in the United States for 1999-2009 were examined using the multiple cause-of-death mortality data. Age-specific and age-adjusted death rates were calculated. For 1999-2009, the average annual age-adjusted death rate was 2.17/100,000 persons. The age-specific rate increased with age until 75-79 years. Males experienced a higher death rate than females. There was no definitive trend in the annual ALS/MND associated death rate, although analyses suggested a possible decrease (p = 0.05); however, the rate increased for persons 20-49 years of age and declined for persons ≥ 65 years of age. The annual rate for males decreased whereas the rate for females showed no change. In conclusion, the suggested decreasing annual ALS/MND associated death rate for 1999-2009 contrasts with earlier reports indicating that the incidence and death rate of ALS were increasing. While the ALS/MND associated death rate slightly increased among adults 20-49 years of age, rates declined among two subpopulations at higher risk for ALS/MND--males and persons ≥ 65 years of age. Continued monitoring of ALS/MND mortality data and additional epidemiological studies will be important to further elucidate these epidemiological trends.

Incidence of amyotrophic lateral sclerosis among American Indians and Alaska natives.

IMPORTANCE: More thorough evaluation of amyotrophic lateral sclerosis (ALS) and motor neuron disease in unique populations could provide clues to etiologies for these idiopathic conditions, and educational programs for American Indian and Alaska Native (AI/AN) people and health care professionals on reservations could improve awareness, understanding, diagnosis, and treatment. In the ongoing search for susceptibility genes, studying particular racial groups, such as AI/ANs,might facilitate the identification of new mutations. OBJECTIVE: To provide better understanding of ALS and secondarily of motor neuron disease among AI/AN people by estimating the incidence and prevalence among AI/ANs served by the Indian Health Service health care system. DESIGN AND SETTING: Analysis of electronic records for AI/ANs with ALS and with motor neuron disease separately for the calendar years 2002-2009 using inpatient and outpatient visit data from the Indian Health Service, which provides health care to eligible AI/ANs nationwide. PARTICIPANTS: Cases were defined by at least 2 inpatient or outpatient visits with the diagnosis. MAIN OUTCOME MEASURES: Crude and age-adjusted incidence and prevalence rates were calculated. RESULTS: Seventy-one AI/ANs were diagnosed with ALS, yielding an average annual crude incidence rate of 0.63 cases per 100 000 and an age-adjusted incidence of 0.92. The median age at onset was 56.0 years and was higher among women than men (62.0 vs 55.0 years; P=.06). Age-specific incidence increased to 70 to 74 years. The crude and age-adjusted point prevalence rates were 2.00 and 4.12, respectively. The crude and age-adjusted incidence rates for motor neuron disease were 1.08 and 1.50, respectively. The annual rates were unchanged across the study period. CONCLUSIONS AND RELEVANCE: The incidence of ALS among AI/ANs appears to be lower than that reported for white populations, a finding congruent with reports of other minority populations. Community-based studies are important to confirm these findings and to examine reasons for the low rate of ALS among AI/ANs.

Parkinson's disease among American Indians and Alaska natives: a nationwide prevalence study.

BACKGROUND: The objective of this study was to determine the prevalence of Parkinson's disease (PD) among American Indian and Alaska Native (AI/AN) people. METHODS: We analyzed records for AI/AN people between 2002 and 2009 using inpatient and outpatient visit data from the Indian Health Service. Crude and age-adjusted prevalence, using the 2000 projected US population as the standard, was determined overall and by age group, sex, period, and region. RESULTS: An estimated 2613 AI/AN people carried the diagnosis of PD (crude prevalence, 143.8/100,000). Prevalence increased with age through 84 years. The age-adjusted rate was 355.7 and was higher among men than women (P < .0001). Rates differed by region (P < .0001). CONCLUSIONS: Parkinson's disease is prevalent among AI/AN people. The prevalence increases with age, varies by geographic region, and is higher among men than women. Community-based studies are needed to define incidence, examine risk factors, and determine reasons for sex and regional differences in PD among AI/AN people.

Risk factors for diarrhea-associated infant mortality in the United States, 2005-2007.

BACKGROUND: Diarrhea-associated deaths among US children increased from the mid-1980s through 2006, particularly among infants. Understanding risk factors for diarrhea-associated death could improve prevention strategies. METHODS: Records of singleton infants with diarrhea listed anywhere on the death certificate were selected from the US Linked Birth/Infant Death data for the period, 2005 to 2007; characteristics of these infants were compared with those of infants who survived their first year. RESULTS: During 2005 to 2007, 1087 diarrhea-associated infant deaths were reported; 86% occurred among low birth weight (LBW, <2500 g) infants. Compared with normal birth weight (NBW, ≥2500 g) infants, LBW infants had a greater mortality rate (risk ratio: 91.9, 95% confidence interval: 77.4-109.0) and younger median age at death (7 versus 15 weeks, P<0.0001). The most common codiagnoses for diarrhea-associated death among LBW and NBW infants were sepsis (26%) and volume depletion (20%), respectively. Among LBW infants, 97% of diarrhea-associated deaths occurred in inpatient settings, whereas 27% of NBW infant deaths occurred in outpatient settings and 5.3% in the decedent's home. Male sex, black race, unmarried status and low 5-minute Apgar score (<7) increased mortality odds among LBW infants whereas, among NBW infants, low 5-minute Apgar score, black race, young maternal age (<25 years) and high birth order (third or more) increased mortality odds. CONCLUSIONS: Efforts to reduce diarrhea-associated morality should focus on understanding and improving management of diarrhea in vulnerable LBW infants. For prevention of diarrhea-associated deaths in NBW infants, educating mothers who fit the high-risk profile regarding home hydration therapy and timely access to medical treatment is important.