Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 38 Records) |
Query Trace: Lange M[original query] |
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Delay of innate immune responses following influenza B virus infection affects the development of a robust antibody response in ferrets
Rowe T , Fletcher A , Lange M , Hatta Y , Jasso G , Wentworth DE , Ross TM . mBio 2025 e0236124 ![]() Due to its natural influenza susceptibility, clinical signs, transmission, and similar sialic acid residue distribution, the ferret is the primary animal model for human influenza research. Antibodies generated following infection of ferrets with human influenza viruses are used in surveillance to detect antigenic drift and cross-reactivity with vaccine viruses and circulating strains. Inoculation of ferrets, with over 1,500 human clinical influenza isolates (1998-2019) resulted in lower antibody responses (HI <1:160) to 86% (387 out of 448) influenza B viruses (IBVs) compared to 2.7% (30 out of 1,094) influenza A viruses (IAVs). Here, we show that the immune responses in ferrets inoculated with IBV were delayed and reduced compared to IAV. Innate gene expression in the upper respiratory tract and blood indicated that IAV generated a strong inflammatory response, including an early activation of the interferon (IFN), whereas IBV elicited a delayed and reduced response. Serum levels of cytokines and IFNs were all much higher following IAV infection than IBV infection. Pro-inflammatory, IFN, TH1/TH2, and T-effector proteins were significantly higher in sera of IAV-infected than IBV-infected ferrets over 28 days following the challenge. Serum levels of Type-I/II/III IFNs were detected following IAV infection throughout this period, whereas Type-III IFN was only late for IBV. An early increase in IFN-lambda corresponded to gene expression following IAV infection. Reduced innate immune responses following IBV infection reflected the subsequent delayed and reduced serum antibodies. These findings may help in understanding the antibody responses in humans following influenza vaccination or infection and consideration of potential addition of innate immunomodulators to overcome low responses. IMPORTANCE: The ferret is the primary animal model for human influenza research. Using a ferret model, we studied the differences in both innate and adaptive immune responses following infection with influenza A and B viruses (IAV and IBV). Antibodies generated following infection of ferrets is used for surveillance assays to detect antigenic drift and cross-reactivity with vaccine viruses and circulating influenza strains. IAV infection of ferrets to generate these reagents resulted in a strong antibody response, but IBV infection generated weak antibody responses. In this study using influenza-infected ferrets, we found that IAV resulted in an early activation of the interferon (IFN) and pro-inflammatory response, whereas IBV showed a delay and reduction in these responses. Serum levels of IFNs and other cytokines or chemokines were much higher in ferrets following IAV infection. These reduced innate responses were reflected the subsequent delayed and reduced antibody responses to IBV in the sera. These findings may help in understanding low antibody responses in humans following influenza B vaccination and infection and may warrant the use of innate immunomodulators to overcome these weak responses. |
Human biomonitoring health-based guidance values: A case study of the HB2GV Dashboard and DEHP
Macey K , Lange R , Apel P , Poddalgoda D , Calafat AM , Kolossa-Gehring M , LaKind JS , Melnyk LJ , Nakayama SF , St-Amand A , Pollock T . Int J Hyg Environ Health 2024 263 114490 In 2022, the International Society of Exposure Science (ISES) International Human Biomonitoring (i-HBM) Working Group launched a free, online repository of biomonitoring guidance values referred to as the Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard. The goal of the Dashboard is to assist global human biomonitoring data users (e.g., risk assessors, risk managers) and human biomonitoring programs with a readily available compilation of guidance values for the general population. The Dashboard contains approximately 600 HB2GVs for over 150 chemicals or their metabolites. Although there are many different types of HB2GVs, most are Biomonitoring Equivalents (BEs), Human Biomonitoring (HBM-I and HBM-II) values, or Human Biomonitoring Guidance Values (HBM-GVs). For users new to human biomonitoring, understanding how the different types of HB2GVs are derived and how to interpret those values in the context of human biomonitoring data can be difficult. Therefore, there is a need to inform users of the differences among available guidance values and to help users identify the HB2GV that could be most suitable for their purposes. Here, we summarize the derivation of HB2GVs for a case study chemical, di-(2-ethylhexyl) phthalate (DEHP). We selected DEHP as there are 36 unique HB2GVs available from three of the most common types of guidance values (i.e., BE, HBM-I value, HBM-GV). We also compare the available HB2GVs with a focus on the differences among their derivation methods, relative quality and confidence, and interpretation. This case study provides guidance on the use of existing HB2GVs for health-based interpretation of human biomonitoring data that may be applied to other chemicals. As with any other type of guidance or regulatory value (e.g., RfDs, MRLs), thoughtful selection and use are strongly encouraged. Appropriately interpreting HBM data with the aid of guidance values can result in improved decision making which, ultimately, could lead to better protection of public health. |
Cognitive assessment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a cognitive substudy of the multi-site clinical assessment of ME/CFS (MCAM)
Lange G , Lin JS , Chen Y , Fall EA , Peterson DL , Bateman L , Lapp C , Podell RN , Natelson BH , Kogelnik AM , Klimas NG , Unger ER . Front Neurosci 2024 18 1460157 INTRODUCTION: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience cognitive problems with attention, information processing speed, working memory, learning efficiency, and executive function. Commonly, patients report worsening of cognitive symptoms over time after physical and/or cognitive challenges. To determine, monitor, and manage longitudinal decrements in cognitive function after such exposures, it is important to be able to screen for cognitive dysfunction and changes over time in clinic and also remotely at home. The primary objectives of this paper were: (1) to determine whether a brief computerized cognitive screening battery will detect differences in cognitive function between ME/CFS and Healthy Controls (HC), (2) to monitor the impact of a full-day study visit on cognitive function over time, and (3) to evaluate the impact of exercise testing on cognitive dysfunction. METHODS: This cognitive sub-study was conducted between 2013 and 2019 across seven U.S. ME/CFS clinics as part of the Multi-Site Clinical Assessment of ME/CFS (MCAM) study. The analysis included 426 participants (261 ME/CFS and 165 HC), who completed cognitive assessments including a computerized CogState Brief Screening Battery (CBSB) administered across five timepoints (T0-T4) at the start of and following a full day in-clinic visit that included exercise testing for a subset of participants (182 ME/CFS and 160 HC). Exercise testing consisted of ramped cycle ergometry to volitional exhaustion. The primary outcomes are performance accuracy and latency (performance speed) on the computerized CBSB administered online in clinic (T0 and T1) and at home (T2-T4). RESULTS: No difference was found in performance accuracy between ME/CFS and HCs whereas information processing speed was significantly slower for ME/CFS at most timepoints with Cohen's d effect sizes ranging from 0.3-0.5 (p < 0.01). The cognitive decline over time on all CBSB tasks was similar for patients with ME/CFS independent of whether exercise testing was included in the clinic visit. CONCLUSION: The challenges of a clinic visit (including cognitive testing) can lead to further cognitive deficits. A single short session of intense exercise does not further reduce speed of performance on any CBSB tasks. |
A scoping review to determine if adverse human health effects are associated with use of organophosphates for mosquito control
Tai Z , Connelly CR , Kuczynski Lange S , Foley N , De Leon Rivera J , Lozano S , Nett RJ . J Med Entomol 2024 Organophosphate insecticides are widely used for adult mosquito control. Although proven effective in reducing mosquito populations and limiting arbovirus transmission, public concern exists regarding potential human health effects associated with organophosphate exposure. The aim of this scoping review was to describe any reported human health conditions associated with organophosphates during their use for adult mosquito control in the United States and Canada. Original peer-reviewed articles published in English language journals from 1 January 2000 to 22 May 2024, were obtained by searching from the databases MEDLINE, EMBASE, Agricultural & Environmental Science Collection, CAB Abstracts, and Scopus. The search identified 6,154 screened articles. Following an independent review, 10 studies were identified that described human health conditions associated with organophosphate exposure during adult mosquito control applications. Of the 10 included studies, only two articles were published within the last 11 years (2013 to 22 May 2024). Three types of study design were represented in the included studies: cohort (n = 5), case study (n = 1), and risk assessment (n = 4). The included studies could not determine causality between exposure to adulticides and development of illness or adverse impacts. Exposure to organophosphates did not contribute to an observed increase in metabolic toxicity, hospitalization rates, or self-reported symptoms and exposure. The available and limited evidence indicates that organophosphates can be used safely to control nuisance mosquitoes or mosquitoes that transmit arboviruses. Continued research regarding the human health effects associated with organophosphate applications for adult mosquito control could help evaluate the basis of the public's concerns and inform public health decision-making. |
A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis.
Miotto P , Tessema B , Tagliani E , Chindelevitch L , Starks AM , Emerson C , Hanna D , Kim PS , Liwski R , Zignol M , Gilpin C , Niemann S , Denkinger CM , Fleming J , Warren RM , Crook D , Posey J , Gagneux S , Hoffner S , Rodrigues C , Comas I , Engelthaler DM , Murray M , Alland D , Rigouts L , Lange C , Dheda K , Hasan R , Ranganathan UDK , McNerney R , Ezewudo M , Cirillo DM , Schito M , Köser CU , Rodwell TC . Eur Respir J 2017 50 (6) ![]() A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype-phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6-90.9%), while for isoniazid it was 78.2% (77.4-79.0%) and their specificities were 96.3% (95.7-96.8%) and 94.4% (93.1-95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1-70.6%) for capreomycin to 88.2% (85.1-90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1-92.5%) for moxifloxacin to 99.5% (99.0-99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis. |
Potential indirect effects of the COVID-19 pandemic on use of emergency departments for acute life-threatening conditions - United States, January-May 2020.
Lange SJ , Ritchey MD , Goodman AB , Dias T , Twentyman E , Fuld J , Schieve LA , Imperatore G , Benoit SR , Kite-Powell A , Stein Z , Peacock G , Dowling NF , Briss PA , Hacker K , Gundlapalli AV , Yang Q . Am J Transplant 2020 20 (9) 2612-2617 This article describes a significant decline in emergency department visits for acute life-threatening conditions during the COVID-19 pandemic, suggesting that patients may be delaying or avoiding care or unable to access care during the pandemic. |
Measuring BMI change among children and adolescents
Freedman DS , Goodwin Davies AJ , Phan TT , Cole FS , Pajor N , Rao S , Eneli I , Kompaniyets L , Lange SJ , Christakis DA , Forrest CB . Pediatr Obes 2022 17 (6) e12889 BACKGROUND: Weight control programs for children monitor BMI changes using BMI z-scores that adjust BMI for the sex and age of the child. It is, however, uncertain if BMIz is the best metric for assessing BMI change. OBJECTIVE: To identify which of 6 BMI metrics is optimal for assessing change. We considered a metric to be optimal if its short-term variability was consistent across the entire BMI distribution. SUBJECTS: 285 643 2- to 17-year-olds with BMI measured 3 times over a 10- to 14-month period. METHODS: We summarized each metric's variability using the within-child standard deviation. RESULTS: Most metrics' initial or mean value correlated with short-term variability (|r| ~ 0.3 to 0.5). The metric for which the within-child variability was largely independent (r = 0.13) of the metric's initial or mean value was the percentage of the 50th expressed on a log scale. However, changes in this metric between the first and last visits were highly (r ≥ 0.97) correlated with changes in %95th and %50th. CONCLUSIONS: Log %50 was the metric for which the short-term variability was largely independent of a child's BMI. Changes in log %50th, %95th, and %50th are strongly correlated. |
Investigation of a SARS-CoV-2 B.1.1.529 (Omicron) Variant Cluster - Nebraska, November-December 2021.
Jansen L , Tegomoh B , Lange K , Showalter K , Figliomeni J , Abdalhamid B , Iwen PC , Fauver J , Buss B , Donahue M . MMWR Morb Mortal Wkly Rep 2021 70 (5152) 1782-1784 ![]() The B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) was first detected in specimens collected on November 11, 2021, in Botswana and on November 14 in South Africa;* the first confirmed case of Omicron in the United States was identified in California on December 1, 2021 (1). On November 29, the Nebraska Department of Health and Human Services was notified of six probable cases(†) of COVID-19 in one household, including one case in a man aged 48 years (the index patient) who had recently returned from Nigeria. Given the patient's travel history, Omicron infection was suspected. Specimens from all six persons in the household tested positive for SARS-CoV-2 by reverse transcription-polymerase chain reaction (RT-PCR) testing on December 1, and the following day genomic sequencing by the Nebraska Public Health Laboratory identified an identical Omicron genotype from each specimen (Figure). Phylogenetic analysis was conducted to determine if this cluster represented an independent introduction of Omicron into the United States, and a detailed epidemiologic investigation was conducted. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.(§). |
Interrelationships among age at adiposity rebound, BMI during childhood, and BMI after age 14 years in an electronic health record database
Freedman DS , Goodwin-Davies AJ , Kompaniyets L , Lange SJ , Goodman AB , Phan TT , Rao S , Eneli I , Forrest CB . Obesity (Silver Spring) 2022 30 (1) 201-208 OBJECTIVE: This study compared the importance of age at adiposity rebound versus childhood BMI to subsequent BMI levels in a longitudinal analysis. METHODS: From the electronic health records of 4.35 million children, a total of 12,228 children were selected who were examined at least once each year between ages 2 and 7 years and reexamined after age 14 years. The minimum number of examinations per child was six. Each child's rebound age was estimated using locally weighted regression (lowess), a smoothing technique. RESULTS: Children who had a rebound age < 3 years were, on average, 7 kg/m(2) heavier after age 14 years than were children with a rebound age ≥ 7 years. However, BMI after age 14 years was more strongly associated with BMI at the rebound than with rebound age (r = 0.57 vs. -0.44). Furthermore, a child's BMI at age 3 years provided more information on BMI after age 14 years than did rebound age. In addition, rebound age provided no information on subsequent BMI if a child's BMI at age 6 years was known. CONCLUSIONS: Although rebound age is related to BMI after age 14 years, a child's BMI at age 3 years provides more information and is easier to obtain. |
Longitudinal Trends in Body Mass Index Before and During the COVID-19 Pandemic Among Persons Aged 2-19 Years - United States, 2018-2020.
Lange SJ , Kompaniyets L , Freedman DS , Kraus EM , Porter R , Blanck HM , Goodman AB . MMWR Morb Mortal Wkly Rep 2021 70 (37) 1278-1283 Obesity is a serious health concern in the United States, affecting more than one in six children (1) and putting their long-term health and quality of life at risk.* During the COVID-19 pandemic, children and adolescents spent more time than usual away from structured school settings, and families who were already disproportionally affected by obesity risk factors might have had additional disruptions in income, food, and other social determinants of health.(†) As a result, children and adolescents might have experienced circumstances that accelerated weight gain, including increased stress, irregular mealtimes, less access to nutritious foods, increased screen time, and fewer opportunities for physical activity (e.g., no recreational sports) (2,3). CDC used data from IQVIA's Ambulatory Electronic Medical Records database to compare longitudinal trends in body mass index (BMI, kg/m(2)) among a cohort of 432,302 persons aged 2-19 years before and during the COVID-19 pandemic (January 1, 2018-February 29, 2020 and March 1, 2020-November 30, 2020, respectively). Between the prepandemic and pandemic periods, the rate of BMI increase approximately doubled, from 0.052 (95% confidence interval [CI] = 0.051-0.052 to 0.100 (95% CI = 0.098-0.101) kg/m(2)/month (ratio = 1.93 [95% CI = 1.90-1.96]). Persons aged 2-19 years with overweight or obesity during the prepandemic period experienced significantly higher rates of BMI increase during the pandemic period than did those with healthy weight. These findings underscore the importance of efforts to prevent excess weight gain during and following the COVID-19 pandemic, as well as during future public health emergencies, including increased access to efforts that promote healthy behaviors. These efforts could include screening by health care providers for BMI, food security, and social determinants of health, increased access to evidence-based pediatric weight management programs and food assistance resources, and state, community, and school resources to facilitate healthy eating, physical activity, and chronic disease prevention. |
Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis.
Verweij PE , Brüggemann RJM , Azoulay E , Bassetti M , Blot S , Buil JB , Calandra T , Chiller T , Clancy CJ , Cornely OA , Depuydt P , Koehler P , Lagrou K , de Lange D , Lass-Flörl C , Lewis RE , Lortholary O , Liu PL , Maertens J , Nguyen MH , Patterson TF , Rijnders BJA , Rodriguez A , Rogers TR , Schouten JA , Wauters J , van de Veerdonk FL , Martin-Loeches I . Intensive Care Med 2021 47 (8) 1-16 PURPOSE: Invasive pulmonary aspergillosis (IPA) is increasingly reported in patients with severe coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Diagnosis and management of COVID-19 associated pulmonary aspergillosis (CAPA) are challenging and our aim was to develop practical guidance. METHODS: A group of 28 international experts reviewed current insights in the epidemiology, diagnosis and management of CAPA and developed recommendations using GRADE methodology. RESULTS: The prevalence of CAPA varied between 0 and 33%, which may be partly due to variable case definitions, but likely represents true variation. Bronchoscopy and bronchoalveolar lavage (BAL) remain the cornerstone of CAPA diagnosis, allowing for diagnosis of invasive Aspergillus tracheobronchitis and collection of the best validated specimen for Aspergillus diagnostics. Most patients diagnosed with CAPA lack traditional host factors, but pre-existing structural lung disease and immunomodulating therapy may predispose to CAPA risk. Computed tomography seems to be of limited value to rule CAPA in or out, and serum biomarkers are negative in 85% of patients. As the mortality of CAPA is around 50%, antifungal therapy is recommended for BAL positive patients, but the decision to treat depends on the patients' clinical condition and the institutional incidence of CAPA. We recommend against routinely stopping concomitant corticosteroid or IL-6 blocking therapy in CAPA patients. CONCLUSION: CAPA is a complex disease involving a continuum of respiratory colonization, tissue invasion and angioinvasive disease. Knowledge gaps including true epidemiology, optimal diagnostic work-up, management strategies and role of host-directed therapy require further study. |
Baseline Asymptomatic Malaria Infection and Immunogenicity of rVSVG-ZEBOV-GP Vaccine: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)
Mahon BE , Simon J , Widdowson MA , Samai M , Rogier E , Legardy-Williams J , Liu K , Schiffer J , Lange J , DeByle C , Pinner R , Schuchat A , Slutsker L , Goldstein S . J Infect Dis 2021 224 (11) 1907-1915 BACKGROUND: The effect of malaria infection on rVSVΔG-ZEBOV-GP (ERVEBO®) immunogenicity is unknown. METHODS: The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-6 Ebola epidemic. In STRIVE's immunogenicity sub-study, participants provided blood samples at baseline, 1, 6, and 9-12 months. Anti-glycoprotein (GP) binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by PCR. RESULTS: Overall, 506 participants enrolled in the immunogenicity sub-study and had ≥1 post-vaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73(14.6%). All GP-ELISA and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants seroresponded by GP-ELISA (≥2-fold rise AND ≥200 EU/ml), while 81.5% seroresponded by PRNT (≥4-fold rise) at ≥1 post-vaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months. CONCLUSION: Asymptomatic adults with and without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower. |
A longitudinal comparison of alternatives to CDC BMI z-scores for children with very high BMIs
Freedman DS , Goodwin Davies AJ , Kompaniyets L , Lange SJ , Goodman AB , Tam Phan TL , Cole FS , Dempsey A , Pajor N , Eneli I , Christakis DA , Forrest CB . J Pediatr 2021 235 156-162 OBJECTIVE: The current CDC BMI z-scores are inaccurate for BMIs ≥ 97(th) percentile. We, therefore, considered 5 alternatives that can be used across the entire BMI distribution: modified BMIz, %CDC95th percentile, extended BMIz, %median, and %median adjusted for the dispersion of BMIs. STUDY DESIGN: We illustrate the behavior of the metrics among children of different ages and BMIs. We then compared the longitudinal tracking of the BMI metrics in electronic health record (EHR) data from 1.17 million children in PEDSnet using the intraclass correlation coefficient (ICC) to determine if one metric was superior. RESULTS: Our examples show that using CDC BMIz for high BMIs can result in nonsensical results. All alternative metrics showed higher tracking than CDC BMIz among children with obesity. Of the alternatives, modified BMIz performed poorly among children with severe obesity, and %median performed poorly among children who did not have obesity at their first visit. The highest ICCs were generally seen for extended BMIz, adjusted %median, and %CDC95(th) percentile. CONCLUSIONS: Based on the examples of differences in the BMI metrics, the longitudinal tracking results, and current familiarity BMI z-scores and percentiles, extended BMIz and extended BMI percentile may be suitable replacements for the current z-scores and percentiles. These metrics are identical to those in the CDC growth charts for BMIs < 95(th) percentile and are superior for very high BMIs. Researchers' familiarity with the current CDC z-scores and clinicians with the CDC percentiles may ease the transition to the extended BMI scale. |
Body Mass Index and Risk for COVID-19-Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death - United States, March-December 2020.
Kompaniyets L , Goodman AB , Belay B , Freedman DS , Sucosky MS , Lange SJ , Gundlapalli AV , Boehmer TK , Blanck HM . MMWR Morb Mortal Wkly Rep 2021 70 (10) 355-361 Obesity* is a recognized risk factor for severe COVID-19 (1,2), possibly related to chronic inflammation that disrupts immune and thrombogenic responses to pathogens (3) as well as to impaired lung function from excess weight (4). Obesity is a common metabolic disease, affecting 42.4% of U.S. adults (5), and is a risk factor for other chronic diseases, including type 2 diabetes, heart disease, and some cancers.(†) The Advisory Committee on Immunization Practices considers obesity to be a high-risk medical condition for COVID-19 vaccine prioritization (6). Using data from the Premier Healthcare Database Special COVID-19 Release (PHD-SR),(§) CDC assessed the association between body mass index (BMI) and risk for severe COVID-19 outcomes (i.e., hospitalization, intensive care unit [ICU] or stepdown unit admission, invasive mechanical ventilation, and death). Among 148,494 adults who received a COVID-19 diagnosis during an emergency department (ED) or inpatient visit at 238 U.S. hospitals during March-December 2020, 28.3% had overweight and 50.8% had obesity. Overweight and obesity were risk factors for invasive mechanical ventilation, and obesity was a risk factor for hospitalization and death, particularly among adults aged <65 years. Risks for hospitalization, ICU admission, and death were lowest among patients with BMIs of 24.2 kg/m(2), 25.9 kg/m(2), and 23.7 kg/m(2), respectively, and then increased sharply with higher BMIs. Risk for invasive mechanical ventilation increased over the full range of BMIs, from 15 kg/m(2) to 60 kg/m(2). As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity. These findings highlight the clinical and public health implications of higher BMIs, including the need for intensive COVID-19 illness management as obesity severity increases, promotion of COVID-19 prevention strategies including continued vaccine prioritization (6) and masking, and policies to ensure community access to nutrition and physical activities that promote and support a healthy BMI. |
Associations between food policy councils and policies that support healthy food access: A national survey of community policy supports
Lange SJ , Calancie L , Onufrak SJ , Reddy KT , Palmer A , Warnock AL . Nutrients 2021 13 (2) 1-13 Food policy councils (FPCs) are one form of community coalition that aims to address challenges to local food systems and enhance availability, accessibility, and affordability of healthy foods for local residents. We used data from the 2014 National Survey of Community-Based Policy and Environmental Supports for Healthy Eating and Active Living, a nationally representative survey of US municipalities (n = 2029), to examine the prevalence of FPCs and cross-sectional associations between FPCs and four types of supports for healthy food access (approaches to help food stores, practices to support farmers markets, transportation-related supports, and community planning documents). Overall, 7.7% of municipalities reported having a local or regional FPC. FPCs were more commonly reported among larger municipalities with ≥50,000 people (29.2%, 95% Confidence Interval (CI): 21.6, 36.8) and western region municipalities (13.2%, 95% CI: 9.6, 16.8). After multivariable adjustment, municipalities with FPCs had significantly higher odds of having all four types of supports, compared to those without FPCs (adjusted odds ratio (aOR) range: 2.4–3.4). Among municipalities with FPCs (n = 156), 41% reported having a local government employee or elected official as a member, and 46% had a designated health or public health representative. Although FPCs were uncommon, municipalities that reported having a local or regional FPC were more likely to report having supports for healthy food access for their residents. |
Percentage of adolescents meeting federal fruit and vegetable intake recommendations - Youth Risk Behavior Surveillance System, United States, 2017
Lange SJ , Moore LV , Harris DM , Merlo CL , Lee SH , Demissie Z , Galuska DA . MMWR Morb Mortal Wkly Rep 2021 70 (3) 69-74 According to the 2020-2025 Dietary Guidelines for Americans, persons should consume fruits and vegetables as part of a healthy eating pattern to reduce their risk for diet-related chronic diseases, such as cardiovascular disease, type 2 diabetes, some cancers, and obesity.* A healthy diet is important for healthy growth in adolescence, especially because adolescent health behaviors might continue into adulthood (1). The U.S. Department of Agriculture (USDA) recommends minimum daily intake of 1.5 cups of fruit and 2.5 cups of vegetables for females aged 14-18 years and 2 cups of fruit and 3 cups of vegetables for males aged 14-18 years.(†) Despite the benefits of fruit and vegetable consumption, few adolescents consume these recommended amounts (2-4). In 2013, only 8.5% of high school students met the recommendation for fruit consumption, and only 2.1% met the recommendation for vegetable consumption (2). To update the 2013 data, CDC analyzed data from the 2017 national and state Youth Risk Behavior Surveys (YRBSs) to describe the percentage of students who met intake recommendations, overall and by sex, school grade, and race/ethnicity. The median frequencies of fruit and vegetable consumption nationally were 0.9 and 1.1 times per day, respectively. Nationally, 7.1% of students met USDA intake recommendations for fruits (95% confidence interval [CI] = 4.0-10.3) and 2.0% for vegetables (upper 95% confidence limit = 7.9) using previously established scoring algorithms. State-specific estimates of the percentage of students meeting fruit intake recommendations ranged from 4.0% (Connecticut) to 9.3% (Louisiana), and the percentage meeting vegetable intake recommendations ranged from 0.6% (Kansas) to 3.7% (New Mexico). Additional efforts to expand the reach of existing school and community programs or to identify new effective strategies, such as social media approaches, might help address barriers and improve adolescent fruit and vegetable consumption. |
Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis
Bisson GP , Bastos M , Campbell JR , Bang D , Brust JC , Isaakadis P , Lange C , Menzies D , Migliori GB , Pape JW , Palmero D , Baghei P , Tabarsi P , Viiklepp P , Vilbrun S , Walsh J , Marks SM . Lancet 2020 396 (10248) 402-411 BACKGROUND: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. METHODS: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. FINDINGS: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. INTERPRETATION: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America. |
Race/Ethnicity, Underlying Medical Conditions, Homelessness, and Hospitalization Status of Adult Patients with COVID-19 at an Urban Safety-Net Medical Center - Boston, Massachusetts, 2020.
Hsu HE , Ashe EM , Silverstein M , Hofman M , Lange SJ , Razzaghi H , Mishuris RG , Davidoff R , Parker EM , Penman-Aguilar A , Clarke KEN , Goldman A , James TL , Jacobson K , Lasser KE , Xuan Z , Peacock G , Dowling NF , Goodman AB . MMWR Morb Mortal Wkly Rep 2020 69 (27) 864-869 As of July 5, 2020, approximately 2.8 million coronavirus disease 2019 (COVID-19) cases and 130,000 COVID-19-associated deaths had been reported in the United States (1). Populations historically affected by health disparities, including certain racial and ethnic minority populations, have been disproportionally affected by and hospitalized with COVID-19 (2-4). Data also suggest a higher prevalence of infection with SARS-CoV-2, the virus that causes COVID-19, among persons experiencing homelessness (5). Safety-net hospitals,(dagger) such as Boston Medical Center (BMC), which provide health care to persons regardless of their insurance status or ability to pay, treat higher proportions of these populations and might experience challenges during the COVID-19 pandemic. This report describes the characteristics and clinical outcomes of adult patients with laboratory-confirmed COVID-19 treated at BMC during March 1-May 18, 2020. During this time, 2,729 patients with SARS-CoV-2 infection were treated at BMC and categorized into one of the following mutually exclusive clinical severity designations: exclusive outpatient management (1,543; 56.5%), non-intensive care unit (ICU) hospitalization (900; 33.0%), ICU hospitalization without invasive mechanical ventilation (69; 2.5%), ICU hospitalization with mechanical ventilation (119; 4.4%), and death (98; 3.6%). The cohort comprised 44.6% non-Hispanic black (black) patients and 30.1% Hispanic or Latino (Hispanic) patients. Persons experiencing homelessness accounted for 16.4% of patients. Most patients who died were aged >/=60 years (81.6%). Clinical severity differed by age, race/ethnicity, underlying medical conditions, and homelessness. A higher proportion of Hispanic patients were hospitalized (46.5%) than were black (39.5%) or non-Hispanic white (white) (34.4%) patients, a finding most pronounced among those aged <60 years. A higher proportion of non-ICU inpatients were experiencing homelessness (24.3%), compared with homeless patients who were admitted to the ICU without mechanical ventilation (15.9%), with mechanical ventilation (15.1%), or who died (15.3%). Patient characteristics associated with illness and clinical severity, such as age, race/ethnicity, homelessness, and underlying medical conditions can inform tailored strategies that might improve outcomes and mitigate strain on the health care system from COVID-19. |
Potential Indirect Effects of the COVID-19 Pandemic on Use of Emergency Departments for Acute Life-Threatening Conditions - United States, January-May 2020.
Lange SJ , Ritchey MD , Goodman AB , Dias T , Twentyman E , Fuld J , Schieve LA , Imperatore G , Benoit SR , Kite-Powell A , Stein Z , Peacock G , Dowling NF , Briss PA , Hacker K , Gundlapalli AV , Yang Q . MMWR Morb Mortal Wkly Rep 2020 69 (25) 795-800 On March 13, 2020, the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. Subsequently, states enacted stay-at-home orders to slow the spread of SARS-CoV-2, the virus that causes COVID-19, and reduce the burden on the U.S. health care system. CDC* and the Centers for Medicare & Medicaid Services (CMS)(dagger) recommended that health care systems prioritize urgent visits and delay elective care to mitigate the spread of COVID-19 in health care settings. By May 2020, national syndromic surveillance data found that emergency department (ED) visits had declined 42% during the early months of the pandemic (1). This report describes trends in ED visits for three acute life-threatening health conditions (myocardial infarction [MI, also known as heart attack], stroke, and hyperglycemic crisis), immediately before and after declaration of the COVID-19 pandemic as a national emergency. These conditions represent acute events that always necessitate immediate emergency care, even during a public health emergency such as the COVID-19 pandemic. In the 10 weeks following the emergency declaration (March 15-May 23, 2020), ED visits declined 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis, compared with the preceding 10-week period (January 5-March 14, 2020). EDs play a critical role in diagnosing and treating life-threatening conditions that might result in serious disability or death. Persons experiencing signs or symptoms of serious illness, such as severe chest pain, sudden or partial loss of motor function, altered mental state, signs of extreme hyperglycemia, or other life-threatening issues, should seek immediate emergency care, regardless of the pandemic. Clear, frequent, highly visible communication from public health and health care professionals is needed to reinforce the importance of timely care for medical emergencies and to assure the public that EDs are implementing infection prevention and control guidelines that help ensure the safety of their patients and health care personnel. |
The effect of comorbid medical and psychiatric diagnoses on chronic fatigue syndrome
Natelson BH , Lin JS , Lange G , Khan S , Stegner A , Unger ER . Ann Med 2019 51 1-18 OBJECTIVE: To determine if presence of co-existing medically unexplained syndromes or psychiatric diagnoses affect symptom frequency, severity or activity impairment in Chronic Fatigue Syndrome. PATIENTS: Sequential Chronic Fatigue Syndrome patients presenting in one clinical practice. DESIGN: Participants underwent a psychiatric diagnostic interview and were evaluated for fibromyalgia, irritable bowel syndrome and/or multiple chemical sensitivity. RESULTS: Current and lifetime psychiatric diagnosis was common (68%) increasing mental fatigue/health but not other illness variables and not with diagnosis of other medically unexplained syndromes. 81% of patients had at least one of these conditions with about a third having all three co-existing syndromes. Psychiatric diagnosis was not associated with their diagnosis. Increasing the number of these unexplained conditions was associated with increasing impairment in physical function, pain and rates of being unable to work. CONCLUSIONS: Patients with Chronic Fatigue Syndrome should be evaluated for current psychiatric conditions because of their impact on patient quality of life, but they do not act as a symptom multiplier for the illness. Other co-existing medically unexplained syndromes are more common than psychiatric co-morbidities in patients presenting for evaluation of medically unexplained fatigue and are also more associated with increased disability and the number and severity of symptoms. Key Messages When physicians see patients with medically unexplained fatigue, they often infer that this illness is due to an underlying psychiatric problem. This paper shows that the presence of co-existing psychiatric diagnoses does not impact on any aspect of the phenomenology of medically unexplained fatigue also known as chronic fatigue syndrome. Therefore, psychiatric status is not an important causal contributor to CFS. In contrast, the presence of other medically unexplained syndromes [irritable bowel syndrome; fibromyalgia and/or multiple chemical sensitivity] do impact on the illness such that the more of these that co-exist the more health-related burdens the patient has. |
Data for decision-making: Exploring the division of nutrition, physical activity, and obesity's data, trends, and maps
Lange SJ , Moore LV , Galuska DA . Prev Chronic Dis 2019 16 E131 Public health practitioners need quick and easy access to reliable surveillance data to monitor states' progress over time, compare benchmarks nationally or among states, and make strategic decisions about priorities and resources. Data, Trends, and Maps (DTM) at https://www.cdc.gov/nccdphp/dnpao/data-trends-maps/index.html is a free, online interactive database that houses and displays data on nutrition, physical activity, breastfeeding, and obesity that practitioners can use for public health action. Created in 2015 by the Centers for Disease Control and Prevention's (CDC) Division of Nutrition, Physical Activity, and Obesity, DTM was updated and relaunched in April 2017 with the capability to customize and download data sets directly; DTM also has other user-friendly features, such as visualization options. Since its relaunch, DTM has received more than 386,000 page views from approximately 110,000 unique visitors. However, the potential exists for more widespread use of DTM if more public health practitioners understood what the site offered and how others have used it in the field. Here, we explain how public health practitioners can explore the most recent state-level data on nutrition, physical activity, breastfeeding, and obesity and use this data to inform programmatic and policy efforts to prevent and control chronic diseases. We demonstrate 3 different ways practitioners can visualize data (ie, Explore by Location, Explore by Topic, and the Open Data Portal) and present 3 real-world examples to highlight DTM's utility as a public health tool. |
Epidemiological aspects of travel-related systemic endemic mycoses: a GeoSentinel analysis, 1997-2017
Salzer HJF , Stoney RJ , Angelo KM , Rolling T , Grobusch MP , Libman M , Lopez-Velez R , Duvignaud A , Asgeirsson H , Crespillo-Andujar C , Schwartz E , Gautret P , Bottieau E , Jordan S , Lange C , Hamer DH . J Travel Med 2018 25 (1) Background: International travel has increased in the past few decades, placing more travellers at risk of acquiring systemic endemic mycoses. There are limited published data on systemic endemic mycoses among international travellers. We report epidemiological characteristics of non-migrant, international travellers who acquired systemic endemic mycoses during travel. Methods: We analysed records of non-migrant international travellers with a confirmed diagnosis of histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis or talaromycosis reported from 1997 through 2017 to GeoSentinel, a global surveillance network now consisting of 70 travel or tropical medicine centres in 31 countries. Results: Sixty-nine records met the inclusion criteria. Histoplasmosis was most frequently reported; the 51 travellers with histoplasmosis had the lowest median age (30 years; range: 8-85) and shortest median duration of travel (12 days; range: 5-154). Coccidioidomycosis was reported in 14 travellers; travellers with coccidioidomycosis were older (median 62 years; range: 22-78) and had the longest median number of days between return from travel and presentation to a GeoSentinel site (55 days; range: 17-273). Almost all travellers with coccidioidomycosis were exposed in the USA. Other systemic endemic mycoses were less frequently reported, including blastomycosis (three travellers) and talaromycosis (one traveller). Conclusions: Although relatively rare, systemic endemic mycoses should be considered as potential travel-related infections in non-migrant international travellers. Epidemiological exposures should be used to guide diagnostic evaluations and treatment. |
Local government retail incentives for healthier food retailers in the USA, 2014
Lange SJ , Moore LV , Galuska DA . Public Health Nutr 2019 22 (13) 1-9 OBJECTIVE: National public health organizations recommend that local governments improve access to healthy foods. One way is by offering incentives for food retailer development and operation, but little is known about incentive use nationwide. We aimed to describe the national prevalence of local government reported incentives to increase access to healthy food options in three major food retail settings (farmers' markets, supermarkets, and convenience or corner (smaller) stores) overall and by municipality characteristics. DESIGN: Cross-sectional study using data from the 2014 National Survey of Community-Based Policy and Environmental Supports for Healthy Eating and Active Living. SETTING: USA, nationally representative survey of 2029 municipalities. PARTICIPANTS: Municipal officials (e.g. city/town managers or planners; n 1853). RESULTS: Overall, 67 % of municipalities reported incentives to support farmers' markets, 34 % reported incentives to encourage opening new supermarkets, and 14 % reported incentives to help existing convenience or corner stores. Municipality characteristics significantly associated with incentive use were larger population size (all settings), location in Midwest v. West (supermarkets, smaller stores), higher poverty level (farmers' markets) and </=50 % of the population non-Hispanic White (supermarkets, smaller stores). The most commonly reported individual incentives were permission of sales on city property for farmers' markets, tax credits for supermarkets and linkage to revitalization projects for smaller stores. CONCLUSIONS: Most municipalities offered food retail incentives for farmers' markets, but fewer used incentives to open new supermarkets or assist existing smaller stores. National data can set benchmarks, provide relative comparisons for communities and identify areas for improvement. |
Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase.
Ezewudo M , Borens A , Chiner-Oms A , Miotto P , Chindelevitch L , Starks AM , Hanna D , Liwski R , Zignol M , Gilpin C , Niemann S , Kohl TA , Warren RM , Crook D , Gagneux S , Hoffner S , Rodrigues C , Comas I , Engelthaler DM , Alland D , Rigouts L , Lange C , Dheda K , Hasan R , McNerney R , Cirillo DM , Schito M , Rodwell TC , Posey J . Sci Rep 2018 8 (1) 15382 ![]() ![]() Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis. |
Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis
Ahmad N , Ahuja SD , Akkerman OW , Alffenaar JC , Anderson LF , Baghaei P , Bang D , Barry PM , Bastos ML , Behera D , Benedetti A , Bisson GP , Boeree MJ , Bonnet M , Brode SK , Brust JCM , Cai Y , Caumes E , Cegielski JP , Centis R , Chan PC , Chan ED , Chang KC , Charles M , Cirule A , Dalcolmo MP , D'Ambrosio L , de Vries G , Dheda K , Esmail A , Flood J , Fox GJ , Frechet-Jachym M , Fregona G , Gayoso R , Gegia M , Gler MT , Gu S , Guglielmetti L , Holtz TH , Hughes J , Isaakidis P , Jarlsberg L , Kempker RR , Keshavjee S , Khan FA , Kipiani M , Koenig SP , Koh WJ , Kritski A , Kuksa L , Kvasnovsky CL , Kwak N , Lan Z , Lange C , Laniado-Laborin R , Lee M , Leimane V , Leung CC , Leung EC , Li PZ , Lowenthal P , Maciel EL , Marks SM , Mase S , Mbuagbaw L , Migliori GB , Milanov V , Miller AC , Mitnick CD , Modongo C , Mohr E , Monedero I , Nahid P , Ndjeka N , O'Donnell MR , Padayatchi N , Palmero D , Pape JW , Podewils LJ , Reynolds I , Riekstina V , Robert J , Rodriguez M , Seaworth B , Seung KJ , Schnippel K , Shim TS , Singla R , Smith SE , Sotgiu G , Sukhbaatar G , Tabarsi P , Tiberi S , Trajman A , Trieu L , Udwadia ZF , van der Werf TS , Veziris N , Viiklepp P , Vilbrun SC , Walsh K , Westenhouse J , Yew WW , Yim JJ , Zetola NM , Zignol M , Menzies D . Lancet 2018 392 (10150) 821-834 BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America. |
Reflections on the State of the Art series on TB and migration, and the way forward
Shah S , Lange C , Lonnroth K . Int J Tuberc Lung Dis 2018 22 (8) 829 OVER THE PAST YEAR, the Grey Journal has taken a bold step towards recognizing the critical importance of migrant health as a public health priority. Since the launch of the State of the Art (SoA) series on TB and migration in August 2017, the challenge of global migration for TB care and prevention has not diminished. Millions have experienced migration—either voluntarily or forced—due to economic hardship, military conflicts, or other disasters.1 Migration has been a fundamental human experience since the beginning of time and is undoubtedly likely to continue. Therefore, as the SoA series has demonstrated, addressing migrant-specific health needs is a shared responsibility of the global health community that entails not only efforts in low-burden countries that receive the majority of migrants, but also strengthening of TB care and prevention in high-burden countries to lower overall TB incidence and minimize risk in future migrants. |
Benefit of the shorter MDR TB treatment regimen in California and modified eligibility criteria
Barry PM , Lowenthal P , True L , Henry L , Schack G , Wendorf K , Flood J , Shah N . Am J Respir Crit Care Med 2017 196 (11) 1488-1489 As consultants for multidrug-resistant (MDR) tuberculosis (TB) cases in California, we read with interest the correspondence from Varaine and colleagues (1) and Lange and colleagues (2) regarding the new World Health Organization–recommended shorter treatment for MDR TB (3). As Varaine and colleagues noted, the importance for short-course treatment eligibility of resistance to drugs other than injectables and fluoroquinolones remains unclear in the recommendations (1). This has implications for both programs that do and those that do not routinely perform susceptibility testing to all second-line drugs. One specific question is whether or not patients who have Mycobacterium tuberculosis organisms that are resistant to ethionamide but have only low-level isoniazid resistance are eligible. Considering these patients eligible makes sense, given the drugs included in the shorter regimen. High-dose isoniazid is likely to be active against organisms with low-level isoniazid resistance, commonly associated with a mutation in the inhA gene that also confers resistance to ethionamide (4–6). The efficacy of high-dose isoniazid for organisms with low-level isoniazid resistance is under study (ClinicalTrials.gov identifier: NCT01936831). Ethionamide is more likely to be active against M. tuberculosis organisms with high-level resistance to isoniazid, associated with a mutation in katG, and that are less commonly resistant to ethionamide (5). The shorter regimen includes both ethionamide and high-dose isoniazid and therefore is likely to be effective against both of these common MDR TB resistance patterns. Lange and colleagues reported that fewer than 8% of patients in Europe with MDR TB would be eligible to be treated with the shorter regimen but did not include information about how many patients’ organisms had low-level isoniazid resistance or an inhA mutation (2). |
Multi-site clinical assessment of myalgic encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and implementation of a prospective/retrospective rolling cohort study
Unger ER , Lin JS , Tian H , Natelson BH , Lange G , Vu D , Blate M , Klimas NG , Balbin EG , Bateman L , Allen A , Lapp CW , Springs W , Kogelnik AM , Phan CC , Danver J , Podell RN , Fitzpatrick T , Peterson DL , Gottschalk CG , Rajeevan MS . Am J Epidemiol 2017 185 (8) 617-626 In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1. |
State-of-the-art series on tuberculosis and migration
Lonnroth K , Shah NS , Lange C . Int J Tuberc Lung Dis 2016 20 (10) 1280-1281 The world health organization’s (WHO’s) global tuberculosis (TB) strategy targets a 90% reduction in global incidence by 2035.1 Low-incidence countries—presently a group of predominantly wealthy nations—are already preparing to move towards TB elimination, defined by less than 1 case per 1 million population.2 Rapid decline of TB, as well as eventual elimination, will not be possible unless TB care and prevention is seen as a shared responsibility across countries. In the age of increasing globalization and migration, no single country or region can successfully move towards TB elimination unless there is a substantial and sustainable global reduction in TB burden. We have been reminded of this by the recent increase in TB incidence in the two low-incidence countries that have received the largest number of asylum seekers during the ongoing wave of migration to Western Europe: in 2015, Germany and Sweden experienced an increase of 30%3 and 22%,4 respectively. | Migration is a fundamental phenomenon of human existence. Throughout history it has been a driver of societal change, economic growth, knowledge-sharing, innovation, and development of language and culture. It has also caused tension and conflicts. With the increasing ease of travel, improved connectivity, and interlinked world economy, the world is experiencing an acceleration of migration that is likely to continue. Although most of it is voluntary and planned, economic hardship, military conflicts, and other disasters force people to migrate. Bearing these conditions in mind, TB control must include variables of globalization and migration in the equation. |
Programmatic management of drug-resistant tuberculosis: An updated research agenda
Mitnick CD , Rodriguez CA , Hatton ML , Brigden G , Cobelens F , Grobusch MP , Horsburgh R , Lange C , Lienhardt C , Oren E , Podewils LJ , Seaworth B , van den Hof S , Daley CL , Gebhard AC , Wares F . PLoS One 2016 11 (5) e0155968 INTRODUCTION: There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. METHODS: Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. RESULTS: Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust. DISCUSSION: Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. CONCLUSION: There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB. |
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