Youth experiencing homelessness (YEH) and sexual and gender minority (SGM) YEH may be at increased risk for infectious diseases due to living arrangements, risk behaviors, and barriers to healthcare access that are dissimilar to those of housed youth and older adults experiencing homelessness. To better understand infectious diseases among YEH populations, we synthesized findings from 12 peer-reviewed articles published between 2012 to 2020 which enumerated YEH or SGM YEH infectious disease burden in locations across the U.S. or Canada. Pathogens presented in the studies were limited to sexually transmitted infections (STIs) and bloodborne infections (BBI). Only three studies enumerated infectious diseases among SGM YEH. There was a dearth of comparison data by housing status (ex., sheltered versus unsheltered youth), SGM identity, or other relevant counterfactual groups in the identified studies. We also introduce three publicly available, national-level surveillance datasets from the U.S. or Canada that quantify certain STIs, BBIs, and tuberculosis among YEH, which may be used for future disease burden assessments. Our review calls for more comprehensive YEH-centered research that includes multimodal data collection and timely disease surveillance to improve estimates of infectious diseases among this vulnerable population.

During March-April 2023, a total of 51 persons reported mild to severe gastrointestinal illness after eating at restaurant A in Bozeman, Montana. The outbreak resulted in multiple severe outcomes, including three hospitalizations and two deaths. After an inspection and temporary restaurant closure, the Montana Department of Public Health and Human Services and Montana's Gallatin City-County Health Department collaborated with CDC to conduct a matched case-control study among restaurant patrons to help identify the source of the outbreak. Consumption of morel mushrooms, which are generally considered edible, was strongly associated with gastrointestinal illness. A dose-response relationship was identified, and consumption of raw morel mushrooms was more strongly associated with illness than was consumption of those that were at least partially cooked. In response to the outbreak, educational public messaging regarding morel mushroom preparation and safety was shared through multiple media sources. The investigation highlights the importance of prompt cross-agency communication and collaboration, the utility of epidemiologic studies in foodborne disease outbreak investigations, and the need for additional research about the impact of morel mushroom consumption on human health. Although the toxins in morel mushrooms that might cause illness are not fully understood, proper preparation procedures, including thorough cooking, might help to limit adverse health effects.

Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a larger set of literature searches conducted to synthesize results from longitudinal studies of potentially modifiable risk factors for childhood ADHD, we present meta-analytic results from 66 studies that examined the associations between early chemical exposures and later ADHD diagnosis or symptoms. Studies were eligible for inclusion if the chemical exposure occurred at least 6 months prior to measurement of ADHD diagnosis or symptomatology. Included papers were published between 1975 and 2019 on exposure to anesthetics (n = 5), cadmium (n = 3), hexachlorobenzene (n = 4), lead (n = 22), mercury (n = 12), organophosphates (n = 7), and polychlorinated biphenyls (n = 13). Analyses are presented for each chemical exposure by type of ADHD outcome reported (categorical vs. continuous), type of ADHD measurement (overall measures of ADHD, ADHD symptoms only, ADHD diagnosis only, inattention only, hyperactivity/impulsivity only), and timing of exposure (prenatal vs. childhood vs. cumulative), whenever at least 3 relevant effect sizes were available. Childhood lead exposure was positively associated with ADHD diagnosis and symptoms in all analyses except for the prenatal analyses (odds ratios (ORs) ranging from 1.60 to 2.62, correlation coefficients (CCs) ranging from 0.14 to 0.16). Other statistically significant associations were limited to organophosphates (CC = 0.11, 95% confidence interval (CI): 0.03-0.19 for continuous measures of ADHD outcomes overall), polychlorinated biphenyls (CC = 0.08, 95% CI: 0.02-0.14 for continuous measures of inattention as the outcome), and both prenatal and childhood mercury exposure (CC = 0.02, 95% CI: 0.00-0.04 for continuous measures of ADHD outcomes overall for either exposure window). Our findings provide further support for negative impacts of prenatal and/or childhood exposure to certain chemicals and raise the possibility that primary prevention and targeted screening could prevent or mitigate ADHD symptomatology. Furthermore, these findings support the need for regular review of regulations as our scientific understanding of the risks posed by these chemicals evolves.

CONTEXT: Lacrimators are used by individuals for personal defense and by police for crowd control during periods of civil unrest. Increased public awareness about their use has raised concerns about their application and safety. OBJECTIVE: To characterize patterns of lacrimator exposures in the United States, we describe temporal trends of calls to poison centers by demographics, substances, medical outcomes, exposure sites, and scenarios. METHODS: A retrospective data analysis was performed for all single-substance lacrimator exposures in the United States reported to the National Poison Data System between 2000 and 2021. Descriptive analyses were performed to examine demographic characteristics, geographic distribution, product types and medical outcomes associated with lacrimator exposures. RESULTS: A total of 107,149 lacrimator exposure calls were identified. There was an overall decrease in calls per year, from 6,521 calls in 2000 to 2,520 in 2020, followed by an increase to 3,311 calls in 2021. A declining trend was observed independent of total poison center call volume. Oleoresin capsicum was the most commonly reported substance (81,990, 76.5%). Individuals ages 19 years and younger accounted for 62% of calls, but adults ages 20 and over were more likely to develop major clinical effects (odds ratio 3.03; 95% confidence interval 1.91-4.81; P < 0.0001). The most common exposure site was "own residence," followed by schools. School exposures accounted for 15.8% of exposures in children ages 6-12 years and 37.7% in adolescents. Among calls with documented scenarios, 19.7% involved unintentional exposures due to children accessing lacrimators. CONCLUSION: Lacrimator exposure calls to United States poison centers decreased from 2000 to 2021. Most calls pertain to oleoresin capsicum and individuals ages 19 and younger. Improper storage allowing children to have access to these chemicals, is a common scenario. Public safety interventions such as education about safe storage and use of lacrimators, improved product design, or regulatory changes may prevent unintentional exposures.

Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence(1-3) resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.

On July 26, 2022, a pediatric nephrologist alerted The Gambia's Ministry of Health (MoH) to a cluster of cases of acute kidney injury (AKI) among young children at the country's sole teaching hospital, and on August 23, 2022, MoH requested assistance from CDC. CDC epidemiologists arrived in The Gambia, a West African country, on September 16 to assist MoH in characterizing the illness, describing the epidemiology, and identifying potential causal factors and their sources. Investigators reviewed medical records and interviewed caregivers to characterize patients' symptoms and identify exposures. The preliminary investigation suggested that various contaminated syrup-based children's medications contributed to the AKI outbreak. During the investigation, MoH recalled implicated medications from a single international manufacturer. Continued efforts to strengthen pharmaceutical quality control and event-based public health surveillance are needed to help prevent future medication-related outbreaks.

BACKGROUND: Kratom, a psychoactive substance, use is an evolving research area that needs more studies to augment the limited literature. Our study examines the association between kratom use categories and mental health and substance use disorders in the U.S. METHODS: We used the 2020 National Survey on Drug Use and Health data (N = 32,893), a cross-sectional survey data, on the U.S. population aged 12 years or older. We used STATA/SE version 16 to perform a multinomial logistic regression analysis to assess our study aims. RESULTS: Bisexuals, compared to heterosexuals, had higher risks of kratom use within the past 30 days (relative risk ratio [RRR]= 2.47, 95% CI= 1.07, 5.71). Major depressive episode was positively associated with kratom use more than 30 days ago (RRR= 2.04, 95% CI= 1.24, 3.34). This association was also observed for mild (RRR= 2.04, 95% CI= 1.38, 3.02), moderate (RRR= 2.25, 95% CI= 1.13, 4.51), or severe alcohol use disorder (RRR= 1.88, 95% CI= 1.05, 3.36); and mild (RRR= 1.98, 95% CI= 1.27, 3.11), moderate (RRR= 2.38, 95% CI= 1.27, 4.45), or severe marijuana use disorder (RRR= 2.13, 95% CI= 1.02, 4.47). Illicit drug other than marijuana use disorder was associated positively with kratom use more than 30 days ago (RRR= 2.81, 95% CI= 1.85, 4.26) and kratom use within the past 30 days (RRR= 5.48, 95% CI= 1.50, 20.02). CONCLUSIONS: Our findings suggested that identifying as bisexual, experiencing depression, alcohol use disorder, or illicit drug use disorder increased the risks of kratom use. There is a need to consider mental health and substance use disorders and sexual identity in kratom use interventions and policies geared toward reducing or preventing kratom use.

COVID-19 outbreaks have been reported in homeless shelters across the United States (1). Many persons experiencing homelessness are older adults or persons with underlying medical conditions, placing them at increased risk for severe COVID-19–associated illness. The proportion of persons experiencing homelessness who are fully vaccinated against COVID-19 in the United States is currently unknown. Many persons experiencing homelessness express a willingness to receive the COVID-19 vaccine (2,3).

Understanding COVID-19 vaccine acceptability among clients and staff of homeless shelters can inform public health efforts focused on communicating with and educating this population about COVID-19 vaccines and thus improve vaccine uptake. The objective of this study was to assess COVID-19 vaccine acceptability and uptake among people in homeless shelters in Detroit, Michigan. A cross-sectional study was conducted from February 9 to 23, 2021. Seventeen homeless shelters were surveyed: seven male-only, three male/female, and seven women and family shelters. All clients and staff aged ≥18 years and able to complete a verbal survey in English or with a translator were eligible to participate; of the 168 individuals approached, 26 declined, leaving a total sample of 106 clients and 36 staff participating in the study. The median client and staff ages were 44 and 54 years, respectively. Most participants (>80%) identified as non-Hispanic Black or African American. Sixty-one (57.5%) clients and 27 (75.5%) staff had already received or planned to receive a COVID-19 vaccination. Twelve (11.3%) clients and four (11.1%) staff were unsure, and 33 (31.1%) clients and five (13.9%) staff did not plan to get vaccinated. Reasons for hesitancy were concerns over side effects (29 clients [64.4%] and seven staff [77.8%]) and unknown long-term health impacts (26 clients [57.8%] and six staff [66.7%]). More than half of the clients had already received or planned to receive the vaccine. Continuing efforts such as vaccine education for hesitant clients and staff and having accessible vaccine events for this population may improve acceptability and uptake.

BACKGROUND: Following the West African Ebola virus disease (EVD) outbreak of 2013-2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. METHODOLOGY/PRINCIPAL FINDINGS: Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. CONCLUSIONS/SIGNIFICANCE: The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.

IN RESPONSE: We thank Drs. Newton and Yeh and Dr. Schattner for emphasizing the need to further understand the relationship between influenza virus infection and acute cardiovascular events. In our analysis based on ICD codes, 4412 patients hospitalized with laboratory-confirmed influenza had acute IHD. Among these, 4.6% had ST-segment elevation MI, 43.6% had non–ST-segment elevation MI, 12% had acute MI without specification of the presence of ST-segment elevation, and 38.4% had other acute IHD not otherwise specified; only 1.4% of patients had unstable angina as the only evidence of acute IHD. For patients with MI, we were unable to further differentiate between type I or II MI because of limitations of the ICD coding system. As for in-hospital outcomes among those with MI, patients in all 3 categories had a similar length of stay (median of 5 days). However, those with ST-segment elevation predictably had the highest percentage of intensive care unit admissions (59.7%), mechanical ventilatory support (32.6%), and in-hospital mortality (26.7%).

Accidental consumption of poisonous mushrooms can result in serious illness and death (1). Reports of severe poisonings from consumption of foraged mushrooms for food or hallucinogenic purposes increased during 1999-2016 (2), and approximately 7,500 poisonous mushroom ingestions were reported annually to poison control centers across the United States (1). To estimate the frequency of emergency department (ED) visits, hospitalizations, and severe adverse outcomes associated with accidental poisonous mushroom ingestion in the United States, CDC analyzed 2016 data from the Healthcare Cost and Utilization Project's* Nationwide Emergency Department Sample (HCUP-NEDS) and National Inpatient Sample (HCUP-NIS) databases as well as 2016-2018 data from three IBM MarketScan sources: Commercial Claims and Encounters (CCAE), Medicare Supplemental and Coordination of Benefits (Medicare), and Multi-State Medicaid databases. During 2016, 1,328 (standard error [SE] = 100) ED visits and 100 (SE = 22) hospitalizations (HCUP data) were associated with accidental poisonous mushroom ingestion. Among 556 patients with a diagnosis of accidental poisonous mushroom ingestion, 48 (8.6%) patients experienced a serious adverse outcome during 2016-2018 (MarketScan data). Serious adverse outcomes were more common among Medicaid-insured patients than among patients with commercial insurance or Medicare (11.5% versus 6.7%, p = 0.049). Because most mushroom poisonings are preventable, wild mushrooms should not be consumed unless they are identified by an expert; increased public health messaging about the potential dangers of mushroom poisoning is needed.

Konopka-Anstadt Jennifer L, Campagnoli Ray, Vincent Annelet, Shaw Jing, Wei Ling, Wynn Nhien T, Smithee Shane E, Bujaki Erika, Te Yeh Ming, Laassri Majid, Zagorodnyaya Tatiana, Weiner Amy J, Chumakov Konstantin, Andino Raul, Macadam Andrew, Kew Olen, Burns Cara C. NPJ vaccines 2020 Mar 5(1) 26

Enormous progress has been made in global efforts to eradicate poliovirus, using live-attenuated Sabin oral poliovirus vaccine (OPV). However, as the incidence of disease due to wild poliovirus has declined, vaccine-derived poliovirus (VDPV) has emerged in areas of low-vaccine coverage. Coordinated global cessation of routine, type 2 Sabin OPV (OPV2) use has not resulted in fewer VDPV outbreaks, and continued OPV use in outbreak-response campaigns has seeded new emergences in low-coverage areas. The limitations of existing vaccines and current eradication challenges warranted development of more genetically stable OPV strains, most urgently for OPV2. Here, we report using codon deoptimization to further attenuate Sabin OPV2 by changing preferred codons across the capsid to non-preferred, synonymous codons. Additional modifications to the 5' untranslated region stabilized known virulence determinants. Testing of this codon-deoptimized new OPV2 candidate (nOPV2-CD) in cell and animal models demonstrated that nOPV2-CD is highly attenuated, grows sufficiently for vaccine manufacture, is antigenically indistinguishable from Sabin OPV2, induces neutralizing antibodies as effectively as Sabin OPV2, and unlike Sabin OPV2 is genetically stable and maintains an attenuation phenotype. In-human clinical trials of nOPV2-CD are ongoing, with potential for nOPV strains to serve as critical vaccine tools for achieving and maintaining polio eradication.

PURPOSE: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN: Retrospective cohort study. METHODS: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM(R) MarketScan(R) Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES: Data related to testing, treatment, and direct medical costs. RESULTS: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV. CONCLUSIONS: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies.

BACKGROUND: Despite strong evidence and national policy supporting type 2 diabetes prevention, little is known about type 2 diabetes prevention in the primary care setting. OBJECTIVE: Our objective was to assess primary care physicians' knowledge and practice regarding perceived barriers and potential interventions to improving management of prediabetes. DESIGN: Cross-sectional mailed survey. PARTICIPANTS: Nationally representative random sample of US primary care physicians (PCPs) identified from the American Medical Association Physician Masterfile. MAIN MEASURES: We assessed PCP knowledge, practice behaviors, and perceptions related to prediabetes. We performed chi-square and Fisher's exact tests to evaluate the association between PCP characteristics and the main survey outcomes. KEY RESULTS: In total, 298 (33%) eligible participants returned the survey. PCPs had limited knowledge of risk factors for prediabetes screening, laboratory diagnostic criteria for prediabetes, and management recommendations for patients with prediabetes. Only 36% of PCPs refer patients to a diabetes prevention lifestyle change program as their initial management approach, while 43% discuss starting metformin for prediabetes. PCPs believed that barriers to type 2 diabetes prevention are both at the individual level (e.g., patients' lack of motivation) and at the system level (e.g., lack of weight loss resources). PCPs reported that increased access to and insurance coverage of type 2 diabetes prevention programs and coordination of referral of patients to these resources would facilitate type 2 diabetes preventive efforts. CONCLUSIONS: Addressing gaps in PCP knowledge may improve the identification and management of people with prediabetes, but system-level changes are necessary to support type 2 diabetes prevention in the primary care setting.

In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

BACKGROUND: Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. METHODS: We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). FINDINGS: We screened 137 EVD survivors from June 2016 - August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0years (IQR 17-35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 - Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P<0.001). INTERPRETATION: EBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.

The 2013-2016 West African Ebola virus disease (EVD) outbreak has been the largest in history with 28,616 cases and 11,310 deaths in the highest transmission countries of Sierra Leone, Guinea, and Liberia.1 Reports of uveitis have emerged in EVD survivors.2-3 Herein we discuss clinical features, multimodality imaging, and long-term management of aggressive, sight-threatening panuveitis, in an EVD survivor, providing insight into the pathogenesis of this condition.

Among the survivors of Ebola virus disease (EVD), complications that include uveitis can develop during convalescence, although the incidence and pathogenesis of EVD-associated uveitis are unknown. We describe a patient who recovered from EVD and was subsequently found to have severe unilateral uveitis during convalescence. Viable Zaire ebolavirus (EBOV) was detected in aqueous humor 14 weeks after the onset of EVD and 9 weeks after the clearance of viremia.

OBJECTIVE: Pertussis causes significant morbidity among adults, children, and especially infants. Since 2006, pertussis vaccination has been recommended for women after delivery. We conducted a prospective, controlled evaluation of in-hospital postpartum pertussis vaccination of birth mothers from October 2009 through July 2010 to evaluate the effectiveness of hospital-based procedures in increasing postpartum vaccination. STUDY DESIGN: The intervention and comparison hospitals are private community facilities, each with 2000-6000 births/year. At the intervention hospital, physician opt-in orders for tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) before discharge were implemented in November 2009, followed by standing orders in February 2010. The comparison hospital maintained standard practice. Randomly selected hospital charts of women after delivery were reviewed for receipt of Tdap and demographic data. We evaluated postpartum Tdap vaccination rates and conducted multivariate analyses to evaluate characteristics that are associated with vaccination. We reviewed 1264 charts (658 intervention hospital; 606 comparison hospital) from women with completed deliveries. RESULTS: Tdap postpartum vaccination was 0% at both hospitals at baseline. In the intervention hospital, the introduction of the opt-in order was followed by an increase in postpartum vaccination to 18%. The introduction of the standing order approach was followed by a further increase to 69% (P < .0001). No postpartum Tdap vaccinations were documented in the comparison hospital. Postpartum Tdap vaccination in the intervention hospital did not differ by demographic characteristics. CONCLUSION: In-hospital ordering procedures substantially increased Tdap vaccination coverage in women after delivery. Opt-in orders increased coverage that increased substantially with standing orders.

OBJECTIVE: To assess the economic benefits associated with hospital-based postpartum Tdap (combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination. METHODS: A decision tree model was constructed to calculate the potential cost-benefit of this strategy from both a health care system and a societal perspective. Probabilities and costs were derived from published literature, data reported to Centers for Disease Control and Prevention, and recommendations from expert panels. The maternal vaccination protection period for infants was defined as 7 months, and 10 years of waning immunity following Tdap for birth mothers was estimated in the model. All cost estimates were inflated to year 2012 US dollars and discounted at a 3% annual discount rate. RESULTS: In the base case from a societal perspective, the expected costs per vaccinated and unvaccinated mother were estimated at $129.27 and $187.97, respectively, suggesting an expected net benefit of $58.70 per vaccinated mother. The overall societal benefits in the cohort of 3.6 million U.S. birth mothers ranged from $52.8-126.8 million, depending on the vaccination coverage level. If including direct medical costs only, the strategy would not generate net savings from a health care system perspective. Annual incidence of pertussis in birth mothers and Tdap efficacy exhibited substantial impact on the model as shown in one-way and two-way sensitivity analyses. CONCLUSIONS: Although postpartum Tdap vaccination is not cost-beneficial from a health care system perspective in the base case, this strategy is likely to generate net benefits from a societal perspective.

Central line-associated bloodstream infection (CLABSI) rates are an important measure of health care quality. However, reputational or financial risks associated with public reporting and disclosure of hospital CLABSI rates may introduce reporting biases, including intentional underreporting. To assess systematic case misclassification of CLABSI to secondary bloodstream infection (BSI; ie, intentional underreporting of CLABSI), the authors assessed data reported to the National Healthcare Safety Network by hospitals in Pennsylvania, the only state in which both CLABSI and secondary BSI reporting are mandatory. CLABSI rates decreased over the 2-year analysis period, but the authors found no evidence of increasing secondary BSI rates, suggesting that systematic case misclassification is not widespread.

BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2.503 billion) to 2010 (2.490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). METHODS: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. FINDINGS: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0.37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. INTERPRETATION: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. FUNDING: Bill & Melinda Gates Foundation.

OBJECTIVE: To estimate the potential economic benefits associated with hospital-based postpartum influenza vaccination. METHODS: We constructed a decision analysis model to estimate the potential cost benefit of this strategy from both a societal perspective and a third-party perspective. We included a hypothetical cohort of 1.47 million U.S. postpartum women, assuming an influenza season beginning September 1 and ending April 30. Probabilities and costs were derived from published literature, Centers for Disease Control and Prevention data, and expert recommendations. We used one-way and two-way sensitivity analyses. All cost estimates were inflated to year 2010 U.S. dollars and discounted at a 3% annual discount rate. RESULTS: From the societal perceptive, the expected costs per vaccinated and unvaccinated mother were $328.45 and $341.02 respectively, resulting in an expected net benefit of $12.57 per vaccinated mother. The overall savings in the cohort were predicted to range from $3.69 to $14.75 million, depending on the vaccination coverage rate. This strategy would be cost-beneficial, holding all other variables to the base case, if the annual maternal influenza attack rate is more than 2.8%, influenza vaccine efficacy is more than 47%, or if vaccine acquisition and administration cost per dose are less than $32.78. The strategy would not generate net savings from the third-party perspective. Sensitivity analyses were robust, but disease incidence and vaccine efficacy were important drivers. CONCLUSION: Our model suggests that postpartum influenza vaccination is a cost-beneficial approach for prevention of maternal and infantile influenza from a societal perspective. LEVEL OF EVIDENCE: III.

BACKGROUND: Pharmacogenomic epidemiology (PGxE) assesses the range of responses to pharmacologic agents in relation to genetic variation in population groups. We analyzed publication trends to describe the emerging field of PGxE. METHODS: We analyzed PGxE literature published from 2001 to 2007 by using the HuGE Navigator, a curated database of abstracts on human genome epidemiology extracted from PubMed. We summarized trends by gene and study design and, for the 4 most cited genes, by associated health outcomes and drugs. RESULTS: In all, 1,855 PGxE articles were indexed from 2001 through 2007, with annual publications increasing more than 15-fold during this period. Observational studies outnumbered clinical trials by a ratio of 10 to 1 (1,660 vs. 178). Just 4 genes together accounted for nearly one-fifth of all publications: ABCB1, CYP2C9, CYP2C19, and CYP2D6. For these 4 genes, the most frequently cited therapeutic category was antineoplastic agent, followed by anticoagulant, antiulcer, and antidepressant. Warfarin was the single most frequently cited drug. CONCLUSIONS: The field of PGxE is growing rapidly, encompassing a large spectrum of diseases and drugs important in clinical practice. Systematic tracking and synthesis of the published literature in PGxE can help identify promising applications and guide translation research.