The intersection of genomics and big data with public health: Opportunities for precision public health.

Muin Khoury and co-authors discuss anticipated contributions of genomics and other forms of large-scale data in public health.

Opioid Prescribing Rates in Nonmetropolitan and Metropolitan Counties Among Primary Care Providers Using an Electronic Health Record System - United States, 2014-2017.

Drug overdose is the leading cause of unintentional injury-associated death in the United States. Among 70,237 fatal drug overdoses in 2017, prescription opioids were involved in 17,029 (24.2%) (1). Higher rates of opioid-related deaths have been recorded in nonmetropolitan (rural) areas (2). In 2017, 14 rural counties were among the 15 counties with the highest opioid prescribing rates.* Higher opioid prescribing rates put patients at risk for addiction and overdose (3). Using deidentified data from the Athenahealth electronic health record (EHR) system, opioid prescribing rates among 31,422 primary care providers† in the United States were analyzed to evaluate trends from January 2014 to March 2017. This analysis assessed how prescribing practices varied among six urban-rural classification categories of counties, before and after the March 2016 release of CDC's Guideline for Prescribing Opioids for Chronic Pain (Guideline) (4). Patients in noncore (the most rural) counties had an 87% higher chance of receiving an opioid prescription compared with persons in large central metropolitan counties during the study period. Across all six county groups, the odds of receiving an opioid prescription decreased significantly after March 2016. This decrease followed a flat trend during the preceding period in micropolitan and large central metropolitan county groups; in contrast, the decrease continued previous downward trends in the other four county groups. Data from EHRs can effectively supplement traditional surveillance methods for monitoring trends in opioid prescribing and other areas of public health importance, with minimal lag time under ideal conditions. As less densely populated areas appear to indicate both substantial progress in decreasing opioid prescribing and ongoing need for reduction, community health care practices and intervention programs must continue to be tailored to community characteristics.

The Public Health Community Platform, Electronic Case Reporting, and the Digital Bridge.

At the intersection of new technology advancements, ever-changing health policy, and fiscal constraints, public health agencies seek to leverage modern technical innovations and benefit from a more comprehensive and cooperative approach to transforming public health, health care, and other data into action. State health agencies recognized a way to advance population health was to integrate public health with clinical health data through electronic infectious disease case reporting. The Public Health Community Platform (PHCP) concept of bidirectional data flow and knowledge management became the foundation to build a cloud-based system connecting electronic health records to public health data for a select initial set of notifiable conditions. With challenges faced and lessons learned, significant progress was made and the PHCP grew into the Digital Bridge, a national governance model for systems change, bringing together software vendors, public health, and health care. As the model and technology advance together, opportunities to advance future connectivity solutions for both health care and public health will emerge.

Potentially Preventable Deaths Among the Five Leading Causes of Death - United States, 2010 and 2014.

Death rates by specific causes vary across the 50 states and the District of Columbia.* Information on differences in rates for the leading causes of death among states might help state health officials determine prevention goals, priorities, and strategies. CDC analyzed National Vital Statistics System data to provide national and state-specific estimates of potentially preventable deaths among the five leading causes of death in 2014 and compared these estimates with estimates previously published for 2010. Compared with 2010, the estimated number of potentially preventable deaths changed (supplemental material at https://stacks.cdc.gov/view/cdc/42472); cancer deaths decreased 25% (from 84,443 to 63,209), stroke deaths decreased 11% (from 16,973 to 15,175), heart disease deaths decreased 4% (from 91,757 to 87,950), chronic lower respiratory disease (CLRD) (e.g., asthma, bronchitis, and emphysema) deaths increased 1% (from 28,831 to 29,232), and deaths from unintentional injuries increased 23% (from 36,836 to 45,331). A better understanding of progress made in reducing potentially preventable deaths in the United States might inform state and regional efforts targeting the prevention of premature deaths from the five leading causes in the United States.

Declines in Opioid Prescribing After a Private Insurer Policy Change - Massachusetts, 2011-2015.

Overdose deaths involving opioid pain medications are epidemic in the United States, in part because of high opioid prescribing rates and associated abuse of these drugs (1). In 2014, nearly 2 million U.S. residents either abused or were dependent on prescription opioids (2). In Massachusetts, unintentional opioid-related overdose deaths, including deaths involving heroin, increased 45% from 2012 to 2013.* In 2014, the rate of these deaths reached 20.0 per 100,000, nearly 2.5 times higher than the U.S. rate overall (3,4). On July 1, 2012, Blue Cross Blue Shield of Massachusetts (BCBSMA), the largest insurer in the state with approximately 2.8 million members,† implemented a comprehensive opioid utilization program after learning that many of its members were receiving new prescriptions with a >30-day supply of opioids. The 2016 CDC Guideline for Prescribing Opioids for Chronic Pain recommends avoiding opioids as a first-line therapy for chronic pain and limiting quantities when initiating opioids for acute pain (5). CDC analyzed BCBSMA prescription claims data for the period 2011-2015 to assess the effect of the new utilization program on opioid prescribing rates. During the first 3 years after policy implementation, the average monthly prescribing rate for opioids decreased almost 15%, from 34 per 1,000 members to 29. The percentage of BCBSMA members per month with current opioid prescriptions also declined. The temporal association between implementation of the program and statistically significant declines in both prescribing rates and proportion of members using opioids suggests that the BCBSMA initiative played a role in reducing the use of prescription opioids among its members. Public and private insurers in the United States could benefit from developing their own best practices for prescription opioid utilization that ensure accessible pain care, while reducing the risk for dependence and abuse associated with these drugs.

Rapidly building global health security capacity--Uganda demonstration project, 2013.

Increasingly, the need to strengthen global capacity to prevent, detect, and respond to public health threats around the globe is being recognized. CDC, in partnership with the World Health Organization (WHO), has committed to building capacity by assisting member states with strengthening their national capacity for integrated disease surveillance and response as required by International Health Regulations (IHR). CDC and other U.S. agencies have reinforced their pledge through creation of global health security (GHS) demonstration projects. One such project was conducted during March-September 2013, when the Uganda Ministry of Health (MoH) and CDC implemented upgrades in three areas: 1) strengthening the public health laboratory system by increasing the capacity of diagnostic and specimen referral networks, 2) enhancing the existing communications and information systems for outbreak response, and 3) developing a public health emergency operations center (EOC) (Figure 1). The GHS demonstration project outcomes included development of an outbreak response module that allowed reporting of suspected cases of illness caused by priority pathogens via short messaging service (SMS; i.e., text messaging) to the Uganda District Health Information System (DHIS-2) and expansion of the biologic specimen transport and laboratory reporting system supported by the President's Emergency Plan for AIDS Relief (PEPFAR). Other enhancements included strengthening laboratory management, establishing and equipping the EOC, and evaluating these enhancements during an outbreak exercise. In 6 months, the project demonstrated that targeted enhancements resulted in substantial improvements to the ability of Uganda's public health system to detect and respond to health threats.

Strengthening global health security capacity--Vietnam demonstration project, 2013.

Over the past decade, Vietnam has successfully responded to global health security (GHS) challenges, including domestic elimination of severe acute respiratory syndrome (SARS) and rapid public health responses to human infections with influenza A(H5N1) virus. However, new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A(H7N9) present continued challenges, reinforcing the need to improve the global capacity to prevent, detect, and respond to public health threats. In June 2012, Vietnam, along with many other nations, obtained a 2-year extension for meeting core surveillance and response requirements of the 2005 International Health Regulations (IHR). During March-September 2013, CDC and the Vietnamese Ministry of Health (MoH) collaborated on a GHS demonstration project to improve public health emergency detection and response capacity. The project aimed to demonstrate, in a short period, that enhancements to Vietnam's health system in surveillance and early detection of and response to diseases and outbreaks could contribute to meeting the IHR core capacities, consistent with the Asia Pacific Strategy for Emerging Diseases. Work focused on enhancements to three interrelated priority areas and included achievements in 1) establishing an emergency operations center (EOC) at the General Department of Preventive Medicine with training of personnel for public health emergency management; 2) improving the nationwide laboratory system, including enhanced testing capability for several priority pathogens (i.e., those in Vietnam most likely to contribute to public health emergencies of international concern); and 3) creating an emergency response information systems platform, including a demonstration of real-time reporting capability. Lessons learned included awareness that integrated functions within the health system for GHS require careful planning, stakeholder buy-in, and intradepartmental and interdepartmental coordination and communication.

Preventable Premature Deaths from the Five Leading Causes of Death in Nonmetropolitan and Metropolitan Counties, United States, 2010-2022.

Problem/Condition: A 2019 report quantified the higher percentage of potentially excess (preventable) deaths in U.S. nonmetropolitan areas compared with metropolitan areas during 2010-2017. In that report, CDC compared national, regional, and state estimates of preventable premature deaths from the five leading causes of death in nonmetropolitan and metropolitan counties during 2010-2017. This report provides estimates of preventable premature deaths for additional years (2010-2022). Period Covered: 2010-2022. Description of System: Mortality data for U.S. residents from the National Vital Statistics System were used to calculate preventable premature deaths from the five leading causes of death among persons aged <80 years. CDC's National Center for Health Statistics urban-rural classification scheme for counties was used to categorize the deaths according to the urban-rural county classification level of the decedent's county of residence (1: large central metropolitan [most urban], 2: large fringe metropolitan, 3: medium metropolitan, 4: small metropolitan, 5: micropolitan, and 6: noncore [most rural]). Preventable premature deaths were defined as deaths among persons aged <80 years that exceeded the number expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates). Preventable premature deaths were calculated separately for the six urban-rural county categories nationally, the 10 U.S. Department of Health and Human Services public health regions, and the 50 states and the District of Columbia. Results: During 2010-2022, the percentage of preventable premature deaths among persons aged <80 years in the United States increased for unintentional injury (e.g., unintentional poisoning including drug overdose, unintentional motor vehicle traffic crash, unintentional drowning, and unintentional fall) and stroke, decreased for cancer and chronic lower respiratory disease (CLRD), and remained stable for heart disease. The percentages of preventable premature deaths from the five leading causes of death were higher in rural counties in all years during 2010-2022. When assessed by the six urban-rural county classifications, percentages of preventable premature deaths in the most rural counties (noncore) were consistently higher than in the most urban counties (large central metropolitan and fringe metropolitan) for the five leading causes of death during the study period.During 2010-2022, preventable premature deaths from heart disease increased most in noncore (+9.5%) and micropolitan counties (+9.1%) and decreased most in large central metropolitan counties (-10.2%). Preventable premature deaths from cancer decreased in all county categories, with the largest decreases in large central metropolitan and large fringe metropolitan counties (-100.0%; benchmark achieved in both county categories in 2019). In all county categories, preventable premature deaths from unintentional injury increased, with the largest increases occurring in large central metropolitan (+147.5%) and large fringe metropolitan (+97.5%) counties. Preventable premature deaths from CLRD decreased most in large central metropolitan counties where the benchmark was achieved in 2019 and increased slightly in noncore counties (+0.8%). In all county categories, preventable premature deaths from stroke decreased from 2010 to 2013, remained constant from 2013 to 2019, and then increased in 2020 at the start of the COVID-19 pandemic. Percentages of preventable premature deaths varied across states by urban-rural county classification during 2010-2022. Interpretation: During 2010-2022, nonmetropolitan counties had higher percentages of preventable premature deaths from the five leading causes of death than did metropolitan counties nationwide, across public health regions, and in most states. The gap between the most rural and most urban counties for preventable premature deaths increased during 2010-2022 for four causes of death (cancer, heart disease, CLRD, and stroke) and decreased for unintentional injury. Urban and suburban counties (large central metropolitan, large fringe metropolitan, medium metropolitan, and small metropolitan) experienced increases in preventable premature deaths from unintentional injury during 2010-2022, leading to a narrower gap between the already high (approximately 69% in 2022) percentage of preventable premature deaths in noncore and micropolitan counties. Sharp increases in preventable premature deaths from unintentional injury, heart disease, and stroke were observed in 2020, whereas preventable premature deaths from CLRD and cancer continued to decline. CLRD deaths decreased during 2017-2020 but increased in 2022. An increase in the percentage of preventable premature deaths for multiple leading causes of death was observed in 2020 and was likely associated with COVID-19-related conditions that contributed to increased mortality from heart disease and stroke. Public Health Action: Routine tracking of preventable premature deaths based on urban-rural county classification might enable public health departments to identify and monitor geographic disparities in health outcomes. These disparities might be related to different levels of access to health care, social determinants of health, and other risk factors. Identifying areas with a high prevalence of potentially preventable mortality might be informative for interventions.

Clinical research and development of tuberculosis diagnostics: moving from silos to synergy.

The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce to review the state of tuberculosis diagnostics development in adult and pediatric populations.

Challenges and controversies in defining totally drug-resistant tuberculosis.

In March 2012, in response to reports of tuberculosis (TB) resistant to all anti-TB drugs, the World Health Organization convened an expert consultation that identified issues to be resolved before defining a new category of highly drug-resistant TB. Proposed definitions are ambiguous, and extensive drug resistance is encompassed by the already defined extensively drug-resistant (XDR) TB. There is no evidence that proposed totally resistant TB differs from strains encompassed by XDR TB. Susceptibility tests for several drugs are poorly reproducible. Few laboratories can test all drugs, and there is no consensus list of all anti-TB drugs. Many drugs are used off-label for highly drug resistant TB, and new drugs formulated to combat resistant strains would render the proposed category obsolete. Labeling TB strains as totally drug resistant might lead providers to think infected patients are untreatable. These challenges must be addressed before defining a new category for highly drug-resistant TB.

Performance of tuberculosis drug susceptibility testing in U.S. laboratories from 1994 to 2008.

We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994 to 2008, implemented by the U.S. Centers for Disease Control and Prevention (CDC). During that period, a total of 57,733 test results for culture isolates were reported by 216 participating laboratories for the first-line antituberculosis drugs used in the United States-isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Using Clinical Laboratory and Standards Institute (CLSI)-recommended concentrations for one or more of three methods, agar proportion (AP), BACTEC460 (Bactec), and MGIT-960 (MGIT), yielded overall agreement of 97.0% for first-line drugs. For susceptible strains, agreement was 98.4%; for resistant strains, agreement was 91.0%, with significantly lower accuracy (chi-square test, P < 0.0001). For resistant strains, overall agreement by methods was 91.3% for AP, 93.0% for Bactec, and 82.6% for MGIT and by drugs was 92.2% for INH, 91.5% for RMP, 79.0% for EMB, and 97.5% for PZA. For some strains, performance by method varied significantly. Use of duplicate strains in the same shipment and repeat strains over time revealed consistent performance even for strains with higher levels of interlaboratory discordance. No overall differences in performance between laboratories were observed based on volume of testing or type of facility (e.g., health department, hospital, independent). By all methods, decreased performance was observed for strains with low-level INH resistance, RMP resistance, and EMB-resistant strains. These results demonstrate a high level of performance in detection of drug-resistant M. tuberculosis in U.S. laboratories.

SARS-CoV-2 Serologic Assay Needs for the Next Phase of the US COVID-19 Pandemic Response.

BACKGROUND: There is a need for validated and standardized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quantitative immunoglobulin G (IgG) and neutralization assays that can be used to understand the immunology and pathogenesis of SARS-CoV-2 infection and support the coronavirus disease 2019 (COVID-19) pandemic response. METHODS: Literature searches were conducted to identify English language publications from peer-reviewed journals and preprints from January 2020 through November 6, 2020. Relevant publications were reviewed for mention of IgG or neutralization assays for SARS-CoV-2, or both, and the methods of reporting assay results. RESULTS: Quantitative SARS-CoV-2 IgG results have been reported from a limited number of studies; most studies used in-house laboratory-developed tests in limited settings, and only two semiquantitative tests have received US Food and Drug Administration (FDA) Emergency Use Authorization (EUA). As of November 6, 2020, there is only one SARS-CoV-2 neutralization assay with FDA EUA. Relatively few studies have attempted correlation of quantitative IgG titers with neutralization results to estimate surrogates of protection. The number of individuals tested is small compared with the magnitude of the pandemic, and persons tested are not representative of disproportionately affected populations. Methods of reporting quantitative results are not standardized to enable comparisons and meta-analyses. CONCLUSIONS: Lack of standardized SARS-CoV-2 quantitative IgG and neutralization assays precludes comparison of results from published studies. Interassay and interlaboratory validation and standardization of assays will support efforts to better understand antibody kinetics and longevity of humoral immune responses postillness, surrogates of immune protection, and vaccine immunogenicity and efficacy. Public-private partnerships could facilitate realization of these advances in the United States and worldwide.

Increasing proportions of advanced pulmonary tuberculosis reported in the United States: are delays in diagnosis on the rise?

RATIONALE: Delays in the diagnosis of tuberculosis (TB) can result in progression to advanced disease. Patients with pulmonary TB and advanced disease are more likely to transmit disease and fail treatment. OBJECTIVES: To examine clinical, epidemiological, and geographic factors associated with advanced pulmonary TB to further understanding of delayed diagnosis and transmission. METHODS: Pulmonary tuberculosis cases in persons older than 15 years of age reported to the U.S. National Tuberculosis Surveillance System with advanced disease (cavitation on chest radiograph and acid-fast bacilli smear-positive sputum result) were compared with those without advanced disease using trend and binomial regression analysis. MEASUREMENTS AND MAIN RESULTS: There were 35,584 cases of advanced pulmonary tuberculosis (APT) and 125,077 cases of non-APT reported from 1993 through 2006. Proportions of pulmonary TB cases with APT increased from 18.5% in 1993 to 26.1% in 2006, and the increase in the proportion of APT was most notable for national TB rates below 6.6 per 100,000. At the county level, the association between APT and low TB incidence has grown incrementally since 2000. The proportion of APT increased greatest among whites (65.4%), the employed (63.3%), and the U.S. born (59.2%). The prevalence of APT was 44% greater among persons with multidrug-resistant TB compared with those without it. CONCLUSIONS: This study highlights the need for TB diagnosis at early stages of the disease to minimize APT and decrease the risk of transmission. Additional efforts should concentrate on reducing time to treatment initiation in low-incidence areas and among groups traditionally seen as being at low risk for TB disease.

Nontuberculous mycobacteria infections and anti-tumor necrosis factor-alpha therapy.

Patients receiving anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy are at increased risk for tuberculosis and other granulomatous diseases, but little is known about illness caused by nontuberculous mycobacteria (NTM) in this setting. We reviewed the US Food and Drug Administration MedWatch database for reports of NTM disease in patients receiving anti-TNF-alpha therapy. Of 239 reports collected, 105 (44%) met NTM disease criteria. Median age was 62 years; the majority of patients (66, 65%) were female, and most (73, 70%) had rheumatoid arthritis. NTM infections were associated with infliximab (n = 73), etanercept (n = 25), and adalimumab (n = 7); most patients were taking prednisone (n = 68, 65%) or methotrexate (n = 58, 55%) concurrently. Mycobacteria avium (n = 52, 50%) was most commonly implicated, and 9 patients (9%) had died at the time their infections were reported. A high rate of extrapulmonary manifestations (n = 46, 44%) was also reported.

Potentially Excess Deaths from the Five Leading Causes of Death in Metropolitan and Nonmetropolitan Counties - United States, 2010-2017.

PROBLEM/CONDITION: A 2017 report quantified the higher percentage of potentially excess (or preventable) deaths in nonmetropolitan areas (often referred to as rural areas) compared with metropolitan areas. In that report, CDC compared national, regional, and state estimates of potentially excess deaths among the five leading causes of death in nonmetropolitan and metropolitan counties for 2010 and 2014. This report enhances the geographic detail by using the six levels of the 2013 National Center for Health Statistics (NCHS) urban-rural classification scheme for counties and extending estimates of potentially excess deaths by annual percent change (APC) and for additional years (2010-2017). Trends were tested both with linear and quadratic terms. PERIOD COVERED: 2010-2017. DESCRIPTION OF SYSTEM: Mortality data for U.S. residents from the National Vital Statistics System were used to calculate potentially excess deaths from the five leading causes of death among persons aged <80 years. CDC's NCHS urban-rural classification scheme for counties was used to categorize the deaths according to the urban-rural county classification level of the decedent's county of residence (1: large central metropolitan [most urban], 2: large fringe metropolitan, 3: medium metropolitan, 4: small metropolitan, 5: micropolitan, and 6: noncore [most rural]). Potentially excess deaths were defined as deaths among persons aged <80 years that exceeded the number expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates). Potentially excess deaths were calculated separately for the six urban-rural county categories nationally, the 10 U.S. Department of Health and Human Services public health regions, and the 50 states and District of Columbia. RESULTS: The number of potentially excess deaths among persons aged <80 years in the United States increased during 2010-2017 for unintentional injuries (APC: 11.2%), decreased for cancer (APC: -9.1%), and remained stable for heart disease (APC: 1.1%), chronic lower respiratory disease (CLRD) (APC: 1.7%), and stroke (APC: 0.3). Across the United States, percentages of potentially excess deaths from the five leading causes were higher in nonmetropolitan counties in all years during 2010-2017. When assessed by the six urban-rural county classifications, percentages of potentially excess deaths in the most rural counties (noncore) were consistently higher than in the most urban counties (large central metropolitan) for the study period. Potentially excess deaths from heart disease increased most in micropolitan counties (APC: 2.5%) and decreased most in large fringe metropolitan counties (APC: -1.1%). Potentially excess deaths from cancer decreased in all county categories, with the largest decreases in large central metropolitan (APC: -16.1%) and large fringe metropolitan (APC: -15.1%) counties. In all county categories, potentially excess deaths from the five leading causes increased, with the largest increases occurring in large central metropolitan (APC: 18.3%), large fringe metropolitan (APC: 17.1%), and medium metropolitan (APC: 11.1%) counties. Potentially excess deaths from CLRD decreased most in large central metropolitan counties (APC: -5.6%) and increased most in micropolitan (APC: 3.7%) and noncore (APC: 3.6%) counties. In all county categories, potentially excess deaths from stroke exhibited a quadratic trend (i.e., decreased then increased), except in micropolitan counties, where no change occurred. Percentages of potentially excess deaths also differed among and within public health regions and across states by urban-rural county classification during 2010-2017. INTERPRETATION: Nonmetropolitan counties had higher percentages of potentially excess deaths from the five leading causes than metropolitan counties during 2010-2017 nationwide, across public health regions, and in the majority of states. The gap between the most rural and most urban counties for potentially excess deaths increased during 2010-2017 for three causes of death (cancer, heart disease, and CLRD), decreased for unintentional injury, and remained relatively stable for stroke. Urban and suburban counties (large central metropolitan and large fringe metropolitan, medium metropolitan, and small metropolitan) experienced increases in potentially excess deaths from unintentional injury during 2010-2017, leading to a narrower gap between the already high (approximately 55%) percentage of excess deaths in noncore and micropolitan counties. PUBLIC HEALTH ACTION: Routine tracking of potentially excess deaths by urban-rural county classification might help public health departments and decision-makers identify and monitor public health problems and focus interventions to reduce potentially excess deaths in these areas.

Reducing Potentially Excess Deaths from the Five Leading Causes of Death in the Rural United States

In 2014, the all-cause age-adjusted death rate in the United States reached a historic low of 724.6 per 100,000 population (1). However, mortality in rural (nonmetropolitan) areas of the United States has decreased at a much slower pace, resulting in a widening gap between rural mortality rates (830.5) and urban mortality rates (704.3) (1). During 1999­2014, annual age-adjusted death rates for the five leading causes of death in the United States (heart disease, cancer, unintentional injury, chronic lower respiratory disease (CLRD), and stroke) were higher in rural areas than in urban (metropolitan) areas (Figure 1). In most public health regions (Figure 2), the proportion of deaths among persons aged <80 years (U.S. average life expectancy) (2) from the five leading causes that were potentially excess deaths was higher in rural areas compared with urban areas (Figure 3). Several factors probably influence the rural-urban gap in potentially excess deaths from the five leading causes, many of which are associated with sociodemographic differences between rural and urban areas. Residents of rural areas in the United States tend to be older, poorer, and sicker than their urban counterparts (3). A higher proportion of the rural U.S. population reports limited physical activity because of chronic conditions than urban populations (4). Moreover, social circumstances and behaviors have an impact on mortality and potentially contribute to approximately half of the determining causes of potentially excess deaths (5).

Leading Causes of Death in Nonmetropolitan and Metropolitan Areas- United States, 1999-2014.

PROBLEM/CONDITION: Higher rates of death in nonmetropolitan areas (often referred to as rural areas) compared with metropolitan areas have been described but not systematically assessed. PERIOD COVERED: 1999-2014 DESCRIPTION OF SYSTEM: Mortality data for U.S. residents from the National Vital Statistics System were used to calculate age-adjusted death rates and potentially excess deaths for nonmetropolitan and metropolitan areas for the five leading causes of death. Age-adjusted death rates included all ages and were adjusted to the 2000 U.S. standard population by the direct method. Potentially excess deaths are defined as deaths among persons aged <80 years that exceed the numbers that would be expected if the death rates of states with the lowest rates (i.e., benchmark states) occurred across all states. (Benchmark states were the three states with the lowest rates for each cause during 2008-2010.) Potentially excess deaths were calculated separately for nonmetropolitan and metropolitan areas. Data are presented for the United States and the 10 U.S. Department of Health and Human Services public health regions. RESULTS: Across the United States, nonmetropolitan areas experienced higher age-adjusted death rates than metropolitan areas. The percentages of potentially excess deaths among persons aged <80 years from the five leading causes were higher in nonmetropolitan areas than in metropolitan areas. For example, approximately half of deaths from unintentional injury and chronic lower respiratory disease in nonmetropolitan areas were potentially excess deaths, compared with 39.2% and 30.9%, respectively, in metropolitan areas. Potentially excess deaths also differed among and within public health regions; within regions, nonmetropolitan areas tended to have higher percentages of potentially excess deaths than metropolitan areas. INTERPRETATION: Compared with metropolitan areas, nonmetropolitan areas have higher age-adjusted death rates and greater percentages of potentially excess deaths from the five leading causes of death, nationally and across public health regions. PUBLIC HEALTH ACTION: Routine tracking of potentially excess deaths in nonmetropolitan areas might help public health departments identify emerging health problems, monitor known problems, and focus interventions to reduce preventable deaths in these areas.

Severe or fatal liver injury in 50 patients in the United States taking rifampin and pyrazinamide for latent tuberculosis infection.

BACKGROUND: Severe liver injuries were attributed to the rifampin and pyrazinamide (RZ) regimen after it was recommended for treating latent tuberculosis infection. Implicating RZ as the likeliest cause required excluding alternative causes. METHODS: US health departments reported data on patients who died or were hospitalized for liver disease within 1 month after taking RZ for latent tuberculosis infection from October 1998 through March 2004. The circumstances were investigated on site for each case. Illness characteristics, reasons for RZ treatment, doses and frequency of administration of pyrazinamide, monitoring during treatment, and causes of liver injury were determined. RESULTS: Liver injury was attributable to RZ use for all 50 patients reported, 12 of whom died. For 47 patients, RZ was the likeliest cause of liver injury. The median patient age was 44 years (range, 17-73 years). Thirty-two patients (64%) were male. Seven (16%) of 43 patients tested had hepatitis C virus antibodies, 1 (2%) of 45 had chronic hepatitis B, 3 (14%) of 22 had positive results of HIV serologic tests, 34 (71%) of 48 had alcohol use noted, and 33 (66%) of 50 were taking additional hepatotoxic medications. Six patients, 2 of whom died, had no predictors for liver disease. Patients who died were older (median age, 52 vs. 42 years; P=.08) and took a greater number of other medications (median number of medications, 4 vs. 2; P=.05) than did those who recovered, but these 2 factors were correlated (P<.01). Thirty-one patients (62%) were monitored according to guidelines, 9 of whom died. CONCLUSIONS: RZ was the likeliest cause of most of these liver injuries, some of which were fatal in spite of monitoring. Fatality was predicted by age or use of other medications, but none of the cofactors showed promise as a reliable clinical predictor of severe liver injury.

National plan for reliable tuberculosis laboratory services using a systems approach. Recommendations from CDC and the Association of Public Health Laboratories Task Force on Tuberculosis Laboratory Services.

Since the mid-1990s, public health laboratories have improved tuberculosis (TB) test performance, which has contributed to the resumption of the decline in TB incidence in the United States. However, to eliminate TB in the United States, further improvements are needed in laboratory services to support TB treatment, prevention, and control. A critical step is the development of an integrated system that ensures prompt and reliable laboratory testing and flow of information among laboratorians, clinicians, and TB-control officials. Challenges to developing such a system include 1) establishing lines of communication among laboratorians, clinicians, and TB-control officials; 2) expediting reporting of laboratory results, which can avoid delayed or inappropriate treatment and missed opportunities to prevent transmission; 3) developing evidence-based recommendations for use of new laboratory technologies; 4) maintaining staff proficiency in light of declining numbers of specimens to test, workforce shortages, and loss of laboratory expertise; and 5) upgrading laboratory information systems and connecting all partners. The report of the Association of Public Health Laboratories Task Force presents a framework to improve the future of TB laboratory services and describes the role of the laboratory in TB treatment and control, Task Force processes, general principles and benchmarks, and steps for the dissemination of the Task Force recommendations. This MMWR expands on the Task Force report by describing specific actions and performance measures to guide development and implementation of an integrated system for providing TB laboratory services. CDC and the Association of Public Health Laboratories have developed these guidelines so that laboratorians, clinicians, public health officials, administrators, and funding entities can work together to ensure that health-care providers and TB-control officials have the information needed to treat TB patients, prevent TB transmission, and ultimately eliminate TB in the United States.

Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005.

In 1994, CDC published the Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in HealthCare Facilities, 1994. The guidelines were issued in response to 1) a resurgence of tuberculosis (TB) disease that occurred in the United States in the mid-1980s and early 1990s, 2) the documentation of several high-profile health-care--associated (previously termed "nosocomial") outbreaks related to an increase in the prevalence of TB disease and human immunodeficiency virus (HIV) coinfection, 3) lapses in infection control practices, 4) delays in the diagnosis and treatment of persons with infectious TB disease, and 5) the appearance and transmission of multidrug-resistant (MDR) TB strains. The 1994 guidelines, which followed statements issued in 1982 and 1990, presented recommendations for TB infection control based on a risk assessment process that classified health-care facilities according to categories of TB risk, with a corresponding series of administrative, environmental, and respiratory protection control measures. The TB infection control measures recommended by CDC in 1994 were implemented widely in health-care facilities in the United States. The result has been a decrease in the number of TB outbreaks in health-care settings reported to CDC and a reduction in health-care-associated transmission of Mycobacterium tuberculosis to patients and health-care workers (HCWs). Concurrent with this success, mobilization of the nation's TB control programs succeeded in reversing the upsurge in reported cases of TB disease, and case rates have declined in the subsequent 10 years. Findings indicate that although the 2004 TB rate was the lowest recorded in the United States since national reporting began in 1953, the declines in rates for 2003 (2.3%) and 2004 (3.2%) were the smallest since 1993. In addition, TB infection rates greater than the U.S. average continue to be reported in certain racial/ethnic populations. The threat of MDR TB is decreasing, and the transmission of M. tuberculosis in health-care settings continues to decrease because of implementation of infection-control measures and reductions in community rates of TB. Given the changes in epidemiology and a request by the Advisory Council for the Elimination of Tuberculosis (ACET) for review and update of the 1994 TB infection control document, CDC has reassessed the TB infection control guidelines for health-care settings. This report updates TB control recommendations reflecting shifts in the epidemiology of TB, advances in scientific understanding, and changes in health-care practice that have occurred in the United States during the preceding decade. In the context of diminished risk for health-care-associated transmission of M. tuberculosis, this document places emphasis on actions to maintain momentum and expertise needed to avert another TB resurgence and to eliminate the lingering threat to HCWs, which is mainly from patients or others with unsuspected and undiagnosed infectious TB disease. CDC prepared the current guidelines in consultation with experts in TB, infection control, environmental control, respiratory protection, and occupational health. The new guidelines have been expanded to address a broader concept; health-care--associated settings go beyond the previously defined facilities. The term "health-care setting" includes many types, such as inpatient settings, outpatient settings, TB clinics, settings in correctional facilities in which health care is delivered, settings in which home-based health-care and emergency medical services are provided, and laboratories handling clinical specimens that might contain M. tuberculosis. The term "setting" has been chosen over the term "facility," used in the previous guidelines, to broaden the potential places for which these guidelines apply.