In May 2023, the Detroit Health Department was notified of four cases of invasive nontypeable Haemophilus influenzae (Hi) disease among students attending the same elementary school and grade, all with illness onsets within 7 days. Three patients were hospitalized, and one died. Most U.S. cases of invasive Hi disease are caused by nontypeable strains. No vaccines against nontypeable or non-type b Hi strains are currently available. Chemoprophylaxis is not typically recommended in response to nontypeable Hi cases; however, because of the high attack rate (four cases among 46 students; 8.7%), rifampin prophylaxis was recommended for household contacts of patients with confirmed cases and for all students and staff members in the school wing where confirmed cases occurred. Only 10.8% of students for whom chemoprophylaxis was recommended took it, highlighting gaps in understanding among caregivers and health care providers about persons for whom chemoprophylaxis was recommended. Public health authorities subsequently enhanced communication and education to the school community, improved coordination with health care partners, and established mass prophylaxis clinics at the school. This outbreak highlights the potential for nontypeable Hi to cause serious illness and outbreaks and the need for chemoprophylaxis guidance for nontypeable Hi disease. Achieving high chemoprophylaxis coverage requires education, communication, and coordination with community and health care partners.

Background Triatomine bugs, the vectors of Chagas disease, associate with vertebrate hosts in highly diverse ecotopes. When these blood-sucking bugs adapt to new microhabitats, their phenotypes may change. Although understanding phenotypic variation is key to the study of adaptive evolution and central to phenotype-based taxonomy, the drivers of phenotypic change and diversity in triatomines remain poorly understood.Methods/Findings We combined a detailed phenotypic appraisal (including morphology and morphometrics) with mitochondrial cytb and nuclear ITS2 DNA-sequence analyses to study Rhodnius ecuadoriensis populations from across the species’ range. We found three major, naked-eye phenotypic variants. Southern-Andean bugs (SW Ecuador/NW Peru) from house and vertebrate-nest microhabitats are typical, light-colored, small bugs with short heads/wings. Northern-Andean bugs (W Ecuador wet-forest palms) are dark, large bugs with long heads/wings. Finally, northern-lowland bugs (coastal Ecuador dry-forest palms) are light-colored and medium-sized. Wing and (size-free) head shapes are similar across Ecuadorian populations, regardless of habitat or naked-eye phenotype, but distinct in Peruvian bugs. Bayesian phylogenetic and multispecies-coalescent DNA-sequence analyses strongly suggest that Ecuadorian and Peruvian populations are two independently-evolving lineages, with little within-lineage structuring/differentiation.Conclusions We report sharp naked-eye phenotypic divergence of genetically similar Ecuadorian R. ecuadoriensis (house/nest southern-Andean vs. palm-dwelling northern bugs; and palm-dwelling Andean vs. lowland); and sharp naked-eye phenotypic similarity of typical, yet genetically distinct, southern-Andean bugs from house and nest (but not palm) microhabitats (SW Ecuador vs. NW Peru). This remarkable phenotypic diversity within a single nominal species likely stems from microhabitat adaptations possibly involving predator-driven selective pressure (yielding substrate-matching camouflage coloration) and a shift from palm-crown to vertebrate-nest microhabitats (yielding smaller bodies and shorter heads and wings). These findings shed new light on the origins of phenotypic diversity in triatomines, warn against excess reliance on phenotype-based triatomine-bug taxonomy, and confirm the Triatominae as an informative model-system for the study of phenotypic change under ecological pressure.Author summary Triatomine bugs feed on the blood of vertebrates including humans and transmit the parasite that causes Chagas disease. The bugs, of which 150+ species are known, are highly diverse in size, shape, and color. Some species look so similar that they are commonly confused, whereas a few same-species populations look so different that they were thought to be separate species. Despite the crucial role of naked-eye phenotypes in triatomine-bug identification and classification (which are essential for vector control-surveillance), the origins of this variation remain unclear. Here, we describe a striking case of phenotypic divergence, with genetically similar bugs looking very different from one another, and phenotypic convergence, with bugs from two genetically distinct populations (likely on their way to speciation) looking very similar – and all within a single nominal species, Rhodnius ecuadoriensis. Phenotypically divergent populations occupy different ecological regions (wet vs. dry) and microhabitats (palm-crowns vs. vertebrate nests), whereas convergent populations occupy man-made and nest (but not palm) microhabitats. These findings suggest that triatomines can ‘respond’ to ecological novelty by changing their external, naked-eye phenotypes as they adapt to new microhabitats. We therefore warn that phenotypic traits such as overall size or color may confound triatomine-bug species identification and classification.

Chemical control of vectors depends on the effective application of formulated insecticides. In this study we evaluated formulated larvicides using a larval bioassay against susceptible Aedes aegypti. The estimated larvicide lethal concentrations for 50% mortality (LC50s) were 25.7 μg/liter (Natular 2EC), 3.13 μg/liter (Abate 4E), 0.43 μg/liter (Altosid), 0.03 μg/liter (Nyguard), and 500.6 ITU/liter (VectoBac12AS containing Bacillus thuringiensis israelensis). Sublethal effects were identified and documented from adults that survived exposure to these estimated LC50s (body size and sex proportion). We observed changes in net growth as measured by adult wing lengths. For those larvae exposed to estimated LC50s, the average size of adults was between 0.1% and 10.6% smaller for males and between 1.1% and 13.6% smaller for females compared to controls. Sex proportions varied between larvicides, but some were significantly different from the control, favoring greater survival of females than males.

OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. METHODS: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. RESULTS: ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. CONCLUSIONS: Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.

BACKGROUND: Triatomine bugs, the vectors of Chagas disease, associate with vertebrate hosts in highly diverse ecotopes. It has been proposed that occupation of new microhabitats may trigger selection for distinct phenotypic variants in these blood-sucking bugs. Although understanding phenotypic variation is key to the study of adaptive evolution and central to phenotype-based taxonomy, the drivers of phenotypic change and diversity in triatomines remain poorly understood. METHODS/RESULTS: We combined a detailed phenotypic appraisal (including morphology and morphometrics) with mitochondrial cytb and nuclear ITS2 DNA sequence analyses to study Rhodnius ecuadoriensis populations from across the species' range. We found three major, naked-eye phenotypic variants. Southern-Andean bugs primarily from vertebrate-nest microhabitats (Ecuador/Peru) are typical, light-colored, small bugs with short heads/wings. Northern-Andean bugs from wet-forest palms (Ecuador) are dark, large bugs with long heads/wings. Finally, northern-lowland bugs primarily from dry-forest palms (Ecuador) are light-colored and medium-sized. Wing and (size-free) head shapes are similar across Ecuadorian populations, regardless of habitat or phenotype, but distinct in Peruvian bugs. Bayesian phylogenetic and multispecies-coalescent DNA sequence analyses strongly suggest that Ecuadorian and Peruvian populations are two independently evolving lineages, with little within-lineage phylogeographic structuring or differentiation. CONCLUSIONS: We report sharp naked-eye phenotypic divergence of genetically similar Ecuadorian R. ecuadoriensis (nest-dwelling southern-Andean vs palm-dwelling northern bugs; and palm-dwelling Andean vs lowland), and sharp naked-eye phenotypic similarity of typical, yet genetically distinct, southern-Andean bugs primarily from vertebrate-nest (but not palm) microhabitats. This remarkable phenotypic diversity within a single nominal species likely stems from microhabitat adaptations possibly involving predator-driven selection (yielding substrate-matching camouflage coloration) and a shift from palm-crown to vertebrate-nest microhabitats (yielding smaller bodies and shorter and stouter heads). These findings shed new light on the origins of phenotypic diversity in triatomines, warn against excess reliance on phenotype-based triatomine-bug taxonomy, and confirm the Triatominae as an informative model system for the study of phenotypic change under ecological pressure .

OBJECTIVE: To assess the cost-effectiveness (CE) of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, as implemented in the Action for Health in Diabetes study. RESEARCH DESIGN AND METHODS: Data were from 4,827 participants during their first 9 years of the study participation from 2001 to 2012. Information on Health Utilities Index Mark 2 (HUI-2) and HUI-3, Short-Form 6D (SF-6D), and Feeling Thermometer (FT), cost of delivering the interventions, and health expenditures was collected during the study. CE was measured by incremental CE ratios (ICERs) in costs per quality-adjusted life year (QALY). Future costs and QALYs were discounted at 3% annually. Costs were in 2012 U.S. dollars. RESULTS: Over the 9 years studied, the mean cumulative intervention costs and mean cumulative health care expenditures were $11,275 and $64,453 per person for ILI and $887 and $68,174 for DSE. Thus, ILI cost $6,666 more per person than DSE. Additional QALYs gained by ILI were not statistically significant measured by the HUIs and were 0.07 and 0.15, respectively, measured by SF-6D and FT. The ICERs ranged from no health benefit with a higher cost based on HUIs to $96,458/QALY and $43,169/QALY, respectively, based on SF-6D and FT. CONCLUSIONS: Whether ILI was cost-effective over the 9-year period is unclear because different health utility measures led to different conclusions.

OBJECTIVE: This study evaluated weight changes after cessation of the 10-year intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study. It was hypothesized that ILI participants would be more likely to gain weight during the 2-year observational period following termination of weight-loss-maintenance counseling than would participants in the diabetes support and education (DSE) control group. METHODS: Look AHEAD was a randomized controlled trial that compared the effects of ILI and DSE on cardiovascular morbidity and mortality in participants with overweight/obesity and type 2 diabetes. Look AHEAD was converted to an observational study in September 2012. RESULTS: Two years after the end of the intervention (EOI), ILI and DSE participants lost a mean (SE) of 1.2 (0.2) kg and 1.8 (0.2) kg, respectively (P = 0.003). In addition, 31% of ILI and 23.9% of DSE participants gained >/= 2% (P < 0.001) of EOI weight, whereas 36.3% and 45.9% of the respective groups lost >/= 2% of EOI weight (P = 0.001). Two years after the EOI, ILI participants reported greater use of weight-control behaviors than DSE participants. CONCLUSIONS: Both groups lost weight during the 2-year follow-up period, but more ILI than DSE participants gained >/= 2% of EOI weight. Further understanding is needed of factors that affected long-term weight change in both groups.

OBJECTIVE: To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]). METHODS: This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes. RESULTS: Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P </= 0.001) in the ILI group. CONCLUSIONS: Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design.

Background: Lifestyle interventions have been shown to improve physical function over the short term; however, whether these benefits are sustainable is unknown. The long-term effects of an intensive lifestyle intervention (ILI) on physical function were assessed using a randomized post-test design in the Look AHEAD trial. Methods: Overweight and obese (body mass index >/= 25 kg/m2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes enrolled in Look AHEAD, a trial evaluating an ILI designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including a 4- and 400-m walk, lower extremity physical performance (expanded Short Physical Performance Battery, SPPBexp), and grip strength approximately 11 years postrandomization and 1.5 years after the intervention was stopped (n = 3,783). Results: Individuals randomized to ILI had lower odds of slow gait speed (<0.8 m/s) compared to those randomized to DSE (adjusted OR [95% CI]: 0.84 [0.71 to 0.99]). Individuals randomized to ILI also had faster gait speed over 4- and 400-m (adjusted mean difference [95% CI]: 0.019 [0.007 to 0.031] m/s, p = .002, and 0.023 [0.012 to 0.034] m/sec, p < .0001, respectively) and higher SPPBexp scores (0.037 [0.011 to 0.063], p = .005) compared to those randomized to DSE. The intervention effect was slightly larger for SPPBexp scores among older versus younger participants (0.081 [0.038 to 0.124] vs 0.013 [-0.021 to 0.047], p = .01). Conclusions: An intensive lifestyle intervention has modest but significant long-term benefits on physical function in overweight and obese middle-aged and older adults with type 2 diabetes. ClinicalTrials.gov Identifier: NCT00017953.

Triatoma brasiliensis species complex was defined as a monophyletic group of the species: T. brasiliensis, T. juazeirensis, T. melanica, and T. sherlocki. An alternative grouping scheme proposed the concept of "Brasiliensis subcomplex" which included the former species together with T. melanocephala, T. petrocchiae, T. lenti, T. tibiamaculata, and T. vitticeps. To evaluate the relationship among these taxa we combined the results obtained with four mitochondrial genes (12S, 16S, COI and Cytb, adding to 1811bp) and geometric morphometric analysis of wings and heads. Panstrongylus megistus was included in the analysis as it was previously found related to T. tibiamaculata, T. melanocephala and T. vitticeps. The results of both molecular and morphometric approaches clearly grouped the species analyzed into two monophyletic units, supported by both genetic and wing variability. The first one (G1) comprises the four species originally included in the T. brasiliensis species complex plus T. lenti and T. petrocchiae. The second group (G2) was composed by T. melanocephala, T. tibiamaculata and T. vitticeps, and remarkably, P. megistus if considering wing variability and phylogenetic results. Nevertheless, geometric morphometrics of heads provided a quantitative measurement that discriminates Panstrongylus from the Triatoma species based on the position of the antennal insertion relative to eyes, as it is used as the generic distinctive character. The discrepancy among approaches questions the validity of this character to define Panstrongylus genus. Independently of the chosen group definition -"T. brasiliensis species complex" or "Brasiliensis subcomplex"-we propose to delimit it to species of G1 that are all associated with the Caatinga biome in the Brazilian Northeast. G2 are the ones associated with the Atlantic Forest biome.

Prospective cohort studies are important tools for identifying causes of disease. However, these studies are susceptible to attrition. When information collected after enrollment is through interview or exam, attrition leads to missing information for nonrespondents. The Agricultural Health Study enrolled 52,394 farmers in 1993-1997 and collected additional information during subsequent interviews. Forty-six percent of enrolled farmers responded to the 2005-2010 interview; 7% of farmers died prior to the interview. We examined whether response was related to attributes measured at enrollment. To characterize potential bias from attrition, we evaluated differences in associations between smoking and incidence of 3 cancer types between the enrolled cohort and the subcohort of 2005-2010 respondents, using cancer registry information. In the subcohort we evaluated the ability of inverse probability weighting (IPW) to reduce bias. Response was related to age, state, race/ethnicity, education, marital status, smoking, and alcohol consumption. When exposure and outcome were associated and case response was differential by exposure, some bias was observed; IPW conditional on exposure and covariates failed to correct estimates. When response was nondifferential, subcohort and full-cohort estimates were similar, making IPW unnecessary. This example provides a demonstration of investigating the influence of attrition in cohort studies using information that has been self-reported after enrollment.

Despite clear evidence that structured weight loss interventions reduce diabetes incidence in high-risk adults, it is unclear whether such benefits extend to prevention of cardiovascular disease (CVD) and other diabetes complications, and this controversy has influenced the scope of recommendations for lifestyle interventions.1 Although results from the Da Qing Diabetes Prevention Follow-up Study2 in China showed reduced CVD mortality, and findings from the Diabetes Prevention Program study3 showed reduced microvascular disease, these benefits were limited to women. Perhaps the biggest source of doubt about the role of weight loss on cardiovascular disease outcomes has come from the Look AHEAD study, which was the largest randomised controlled trial designed specifically to test the effect of lifestyle-based weight loss on CVD incidence in people with type 2 diabetes, and achieved perhaps the largest long-term cumulative weight loss ever for a major trial.4 Although the study showed benefits of the weight loss intervention on diverse outcomes, including chronic kidney disease, disability, depression, and sleep quality, there was no significant effect on CVD, which remains the single largest cause of morbidity and mortality in most adult populations.5, 6, 7

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow-up continued for a median of 11.3 years at 16 academic centers. 5145 persons aged 45 - 76 with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self-report and confirmed with central adjudication of medical records.The baseline mean age of participants was 59 years, 60% were women, 63% were Caucasian, and the mean BMI was 36 kg/m2 . Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. 731 participants had a confirmed incident fracture (358 in DSE v. 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR = 1.39, 95% CI 1.02, 1.89).An intensive lifestyle intervention resulting in long term weight loss in overweight / obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted. This article is protected by copyright. All rights reserved.

OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) trial was a randomized controlled clinical trial to compare the effects of 10 years of intensive lifestyle intervention (ILI) with a control condition of diabetes support and education (DSE) on health outcomes in over 5,000 participants with type 2 diabetes. The ILI had significantly greater weight losses than DSE throughout the trial. The goal of this analysis is to describe the cost of delivering the intervention. METHODS: The ILI was designed to promote weight loss and increase physical activity. It involved a combination of group plus individual intervention sessions, with decreasing frequency of contact over the 10 years. The intervention incorporated a variety of strategies, including meal replacement products, to improve weight loss outcomes. The costs of intervention delivery were derived from staff surveys of effort and from records of intervention materials from the 16 US academic clinical trial sites. Costs were calculated from the payer perspective and presented in 2012 dollars. RESULTS: During the first year, when intervention delivery was most intensive, the annual cost of intervention delivery, averaged (standard deviation) across clinical sites, was $2,864.6 ($513.3) per ILI participant compared with $202.4 ($76.6) per DSE participant. As intervention intensity declined, costs decreased, such that from years 5 to 9 of the trial, the annual cost of intervention was $1,119.8 ($227.7) per ILI participant and $102.9 ($33.0) per DSE participant. Staffing accounted for the majority of costs throughout the trial, with meal replacements and materials to promote adherence accounting for smaller shares. CONCLUSIONS: The sustained weight losses produced by the Look AHEAD intervention were supported by intervention costs that were within the range of other weight loss programmes. Future work will include an evaluation of the cost-effectiveness of the ILI and will contain additional follow-up data.

For this study, we abstracted data on 693 avian fossil specimens from 398 publications to determine preservation biases in the avian fossil record. Our results show that dissociated wing and leg bones are the most commonly preserved avian skeletal elements and they are preferentially preserved in environments of high erosion and reworking potential—notably continental shelf marine environments. Using bivariate descriptive displays and multivariable regression analyses, we investigated the trends and associations between well-preserved avian specimens (i.e., fully- or partially-articulated) and a variety of taphonomic factors, including depositional environment, body size, and palaeoclimate. The regression model shows that well-preserved specimens are independently associated with depositional environments of low reworking potential commensurate with low energy systems, warm and humid climates, and smaller bird body size. Our results also indicate that fossils of smaller birds are less common than those of larger birds, but they are more often well-preserved. Bivariate analyses revealed that five times as many articulated specimens are found in warm and humid climates as in cool or dry climates, and this association persists in the multivariable regression model. Warm climates, the strongest predictor of better skeletal preservation, may be underestimated as a source of taphonomic bias in the avian fossil record, possibly because of the indirect nature of climate effects. Rapid burial events, such as volcanic ash accumulations and mudflows, are recognised for their influence on preservation, but climate-related storm events may be more important to avian taphonomy than previously understood. Our analyses indicate that geologic processes leading to high quality preservation of avian fossils are closely associated with climate. Additional studies, based both on fossils and modern taphonomic experiments, with improved collection of climate-related data, are needed to advance our understanding of avian taphonomy.

BACKGROUND: Numerous important characteristics of adult arthropods are related to their size; this is influenced by conditions experienced as immatures. Arthropods cultured in the laboratory for research, or mass-reared for novel control methods, must therefore be of a standard size range and known quality so that results are reproducible. METHODS: A simple two-step technique to assess laboratory culture methods was demonstrated using the mosquito Anopheles gambiae s.s. as a model. First, the ranges of key development outcomes were determined using various diet levels. The observed outcomes described the physiologically constrained limits. Secondly, the same outcomes were measured when using a standard operating procedure (SOP) for comparison with the determined ranges. RESULTS: The standard method resulted in similar development rates to those of high and medium diets, wing length between those resulting from the high and medium diets, and larval survival exceeding all benchmark diet level values. The SOP used to produce experimental material was shown to produces high-quality material, relative to the biologically constrained limits. CONCLUSIONS: The comparison between all possible phenotypic outcomes, as determined by biological constraints, with those outcomes obtained using a given rearing protocol is termed "benchmarking". A method is here demonstrated which could be easily adapted to other arthropods, to objectively assess important characters obtained, and methods used, during routine culture that may affect outcomes of research.

OBJECTIVE: To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial. RESEARCH DESIGN AND METHODS: A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years. RESULTS: ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385-7,175); however, these were not evident among individuals with a history of cardiovascular disease. CONCLUSIONS: Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs.

BACKGROUND: In a phase 3, randomized clinical trial (PREVENT TB) of 8053 people with latent tuberculosis infection, 12 once-weekly doses of rifapentine and isoniazid had good efficacy and tolerability. Children received higher rifapentine milligram per kilogram doses than adults. In the present pharmacokinetic study (a component of the PREVENT TB trial), rifapentine exposure was compared between children and adults. METHODS: Rifapentine doses in children ranged from 300 to 900 mg, and adults received 900 mg. Children who could not swallow tablets received crushed tablets. Sparse pharmacokinetic sampling was performed with 1 rifapentine concentration at 24 hours after drug administration (C24). Rifapentine area under concentrationtime curve (AUC) was estimated from a nonlinear, mixed effects regression model (NLME). RESULTS: There were 80 children (age: median, 4.5 years; range, 2-11 years) and 77 adults (age: median, 40 years; all >18 years) in the study. The geometric mean rifapentine milligram per kilogram dose was greater in children than in adults (children, 23 mg/kg; adults, 11 mg/kg). Rifapentine geometric mean AUC and C24 were 1.3-fold greater in children (all children combined) than in adults. Children who swallowed whole tablets had 1.3-fold higher geometric mean AUC than children who received crushed tablets, and children who swallowed whole tablets had a 1.6-fold higher geometric mean AUC than adults. The higher rifapentine doses in children were well tolerated. To obtain rifapentine exposures comparable in children to adults, dosing algorithms modeled by NLME were developed. CONCLUSIONS: A 2-fold greater rifapentine dose for all children resulted in a 1.3-fold higher AUC compared to adults administered a standard dose. Use of higher weight-adjusted rifapentine doses for young children are warranted to achieve systemic exposures that are associated with successful treatment of latent tuberculosis infection in adults.

SETTING: Twenty tuberculosis (TB) clinics in the United States and Canada. OBJECTIVE: To evaluate the efficacy and safety of a 6- month intermittent regimen of rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB) in human immunodeficiency virus (HIV) negative patients with culture-confirmed pulmonary or extra-pulmonary tuberculosis and either isoniazid (INH) resistance or INH intolerance. DESIGN: Patients were enrolled in a single-arm clinical trial to receive intermittent dosing after at least 14 initial daily doses of RMP+PZA+EMB. Treatment was continued twice (BIW) or thrice weekly (TIW) per physician/patient preference for a total of 6 months, with 2 years of follow-up for relapse after treatment. RESULTS: From 1999 to 2004, 98 patients were enrolled, 78 with reported INH resistance and 20 with INH intolerance. BIW dosing was used in 77 and TIW in 21. Study treatment was completed in 73 (74%). Reasons for discontinuation were hepatic adverse events (n = 12), other adverse effects (n = 3) and other reasons (n = 10). Failure (n = 1) and relapse (n = 2) occurred in 3 (3.5%, 95%CI 1.2-9.8) of 86 patients eligible for efficacy analysis, all occurring in patients with cavitary, acid-fast bacilli smear-positive pulmonary TB. CONCLUSIONS: Intermittent RMP+PZA+EMB appears to be effective in HIV-negative patients, but the regimen is poorly tolerated, possibly due to the prolonged use of PZA. Alternative regimens of lower toxicity are needed.

OBJECTIVE: To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people. METHODS: SLE cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist-judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002-2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age-standardized rates were computed, and capture-recapture was performed to estimate underascertainment of cases. RESULTS: The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0-6.1) and 72.8 (95% CI 70.8-74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture-recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males. Among incident cases, the mean +/- SD age at diagnosis was 39.3 +/- 16.6 years. Black SLE patients had a higher proportion of renal disease and end-stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean +/- SD 34.4 +/- 14.9 years versus 41.9 +/- 21.3 years; P = 0.05). CONCLUSION: SLE prevalence was higher than has been described in most other population-based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2-fold increases in SLE incidence and prevalence, and increased proportions of renal disease and progression to ESRD as compared to white patients.

BACKGROUND: Group A Streptococcus (GAS) is an important bacterial cause of life-threatening illness among the elderly. Public health officials investigated a protracted GAS outbreak in a skilled nursing facility in Georgia housing patients requiring 24-hour nursing or rehabilitation, to prevent additional cases. METHODS: We defined a case as illness in a skilled nursing facility resident with onset after January 2009 with GAS isolated from a usually sterile (invasive) or nonsterile site (noninvasive). Cases were "recurrent" if >1 month elapsed between episodes. We evaluated infection control practices, performed a GAS carriage study, emm-typed available GAS isolates, and conducted a case-control study of risk factors for infection. RESULTS: Three investigations, spanning 36 months, identified 19 residents with a total of 24 GAS infections: 15 invasive (3 recurrent) and 9 noninvasive (2 recurrent) episodes. All invasive cases required hospitalization; 4 patients died. Seven residents were GAS carriers. All invasive cases and resident carrier isolates were type emm 11.0. We observed hand hygiene lapses, inadequate infection documentation, and more frequent wound care staff turnover on wing A versus wing B. Risk factors associated with infection in multivariable analysis included living on wing A (odds ratio [OR], 3.4; 95% confidence interval [CI], .9-16.4) and having an indwelling line (OR, 5.6; 95% CI, 1.2-36.4). Cases ceased following facility-wide chemoprophylaxis in July 2012. CONCLUSIONS: Staff turnover, compromised skin integrity in residents, a suboptimal infection control program, and lack of awareness of infections likely contributed to continued GAS transmission. In widespread, prolonged GAS outbreaks in skilled nursing facilities, facility-wide chemoprophylaxis may be necessary to prevent sustained person-to-person transmission.

A wildlife hospital and rehabilitation center in northwestern United States received several big brown bats with necrosuppurative osteomyelitis in multiple joints. Wing and joint tissues were positive by PCR for poxvirus. Thin-section electron microscopy showed poxvirus particles within A-type inclusions. Phylogenetic comparison supports establishment of a new genus of Poxviridae.

BACKGROUND: Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS: In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS: The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS: An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).

CONTEXT: The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear. OBJECTIVE: To examine the association of a long-term intensive weight-loss intervention with the frequency of remission from type 2 diabetes to prediabetes or normoglycemia. DESIGN, SETTING, AND PARTICIPANTS: Ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001-April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes. INTERVENTIONS: Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n=2241) or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n=2262). MAIN OUTCOME MEASURES: Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A(1c) <6.5% with no antihyperglycemic medication). RESULTS Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 (net difference, -7.9%; 95% CI, -8.3% to -7.6%) and at year 4 (-3.9%; 95% CI, -4.4% to -3.5%) and had greater fitness increases at year 1 (net difference, 15.4%; 95% CI, 13.7%-17.0%) and at year 4 (6.4%; 95% CI, 4.7%-8.1%) (P <.001 for each). The ILI group was significantly more likely to experience any remission (partial or complete), with prevalences of 11.5% (95% CI, 10.1%-12.8%) during the first year and 7.3% (95% CI, 6.2%-8.4%) at year 4, compared with 2.0% for the DSE group at both time points (95% CIs, 1.4%-2.6% at year 1 and 1.5%-2.7% at year 4) (P <.001 for each). Among ILI participants, 9.2% (95% CI, 7.9%-10.4%), 6.4% (95% CI, 5.3%-7.4%), and 3.5% (95% CI, 2.7%-4.3%) had continuous, sustained remission for at least 2, at least 3, and 4 years, respectively, compared with less than 2% of DSE participants (1.7% [95% CI, 1.2%-2.3%] for at least 2 years; 1.3% [95% CI, 0.8%-1.7%] for at least 3 years; and 0.5% [95% CI, 0.2%-0.8%] for 4 years). CONCLUSIONS: In these exploratory analyses of overweight adults, an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education. However, the absolute remission rates were modest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00017953.

BACKGROUND: Since 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB. METHODS: We analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred. RESULTS: The overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (P <.001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were greatest in terms of percentage deviation from expected among persons who had been in the United States less than 2 years. Among U.S.-born persons, the declines in percentage deviation from expected were greatest among homeless persons and substance users. Independent information systems (NTSS, TB prescription claims, and public health laboratories) reported similar patterns of declines. Genotyping data did not suggest sudden decreases in recent transmission. CONCLUSIONS: Our assessments show that the decline in reported TB was not an artifact of changes in surveillance methods; rather, similar declines were found through multiple data sources. While the steady decline of TB cases before 2009 suggests ongoing improvement in TB control, we were not able to identify any substantial change in TB control activities or TB transmission that would account for the abrupt decline in 2009. It is possible that other multiple causes coincident with economic recession in the United States, including decreased immigration and delayed access to medical care, could be related to TB declines. Our findings underscore important needs in addressing health disparities as we move towards TB elimination in the United States.

BACKGROUND: Lifestyle interventions produce shortterm improvements in glycemia and cardiovascular disease (CVD) risk factors in individuals with type 2 diabetes mellitus, but no long-term data are available. We examined the effects of lifestyle intervention on changes in weight, fitness, and CVD risk factors during a 4-year study. METHODS: The Look AHEAD (Action for Health in Diabetes) trial is a multicenter randomized clinical trial comparing the effects of an intensive lifestyle intervention (ILI) and diabetes support and education (DSE; the control group) on the incidence of major CVD events in 5145 overweight or obese individuals (59.5% female; mean age, 58.7 years) with type 2 diabetes mellitus. More than 93% of participants provided outcomes data at each annual assessment. RESULTS: Averaged across 4 years, ILI participants had a greater percentage of weight loss than DSE participants (-6.15% vs -0.88%; P < .001) and greater improvements in treadmill fitness (12.74% vs 1.96%; P < .001), hemoglobin A1c level (-0.36% vs -0.09%; P < .001), systolic (-5.33 vs -2.97 mm Hg; P < .001) and diastolic (-2.92 vs -2.48 mm Hg; P=.01) blood pressure, and levels of high-density lipoprotein cholesterol (3.67 vs 1.97 mg/dL; P < .001) and triglycerides (-25.56 vs -19.75 mg/dL; P < .001). Reductions in low-density lipoprotein cholesterol levels were greater in DSE than ILI participants (-11.27 vs -12.84 mg/dL; P=.009) owing to greater use of medications to lower lipid levels in the DSE group. At 4 years, ILI participants maintained greater improvements than DSE participants in weight, fitness, hemoglobin A1c levels, systolic blood pressure, and highdensity lipoprotein cholesterol levels. CONCLUSIONS: Intensive lifestyle intervention can produce sustained weight loss and improvements in fitness, glycemic control, and CVD risk factors in individuals with type 2 diabetes. Whether these differences in risk factors translate to reduction in CVD events will ultimately be addressed by the Look AHEAD trial. TRIAL REGISTRATION: clinicaltrials.gov IDENTIFIER: NCT00017953 2010 American Medical Association. All rights reserved.