Latent Tuberculosis Screening Among New Users of a Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drug: Gaps in Screening Overall and Among Janus Kinase Inhibitors.

OBJECTIVE: We combined claims and electronic health record (EHR) data to provide contemporary and accurate estimates of latent tuberculosis (TB) screening among new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) and assess potential gaps in testing by drug type, patient characteristics, and practice. METHODS: Our denominator population was patients in the Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare using a b/tsDMARD in 2018 without a claim or prescription in the year prior. TB screening was assessed in both Medicare and RISE 1 and 3 years before the medication start date. We calculated the proportion screened overall, by medication class, and by practice. We tested for demographic differences in screening using logistic regression. RESULTS: In the year before drug starts, 65.6% of patients had any TB screening; in a 3-year window, 72.9% had any TB screening. Rates of screening within 1 year by drug type were greater or equal to the overall screening rate for most drugs except for JAK inhibitors (JAKis) (46%) and interleukin-17 inhibitors (IL-17is) (11.5%). A lower proportion of Hispanic and Asian patients were screened compared with White patients. Practice screening rates ranged from 20.0% to 92.9% of patients within 1 year. CONCLUSION: We report higher screening rates than have previously been published because of combining claims and EHR data. However, important safety gaps remain, namely, reduced screening among new users of a JAKi or IL-17i and among Asian and Hispanic patients, as well as low-performing practices. Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed.

Frequency of Routine Testing for Coronavirus Disease 2019 (COVID-19) in High-risk Healthcare Environments to Reduce Outbreaks.

Routine asymptomatic testing strategies for COVID-19 have been proposed to prevent outbreaks in high-risk healthcare environments. We used simulation modeling to evaluate the optimal frequency of viral testing. We found that routine testing substantially reduces risk of outbreaks, but may need to be as frequent as twice weekly.

Frequency of routine testing for COVID-19 in high-risk healthcare environments to reduce outbreaks.

Routine asymptomatic testing strategies for COVID-19 have been proposed to prevent outbreaks in high-risk healthcare environments. We used simulation modeling to evaluate the optimal frequency of viral testing. We found that routine testing substantially reduces risk of outbreaks, but may need to be as frequent as twice weekly.

Willingness to Take Multidrug-resistant Tuberculosis (MDR-TB) Preventive Therapy Among Adult and Adolescent Household Contacts of MDR-TB Index Cases: An International Multisite Cross-sectional Study.

BACKGROUND: Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. METHODS: In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. RESULTS: From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). CONCLUSIONS: The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.

Investigating the relationship between weather and violence in Baltimore, Maryland, USA.

BACKGROUND: It is a common refrain at major urban trauma centers that caseloads increase in the heat of the summer. Several previous studies supported this assertion, finding trauma admissions and crime to correlate positively with temperature. We examined links between weather and violence in Baltimore, MD, through trauma presentation to Johns Hopkins Hospital and crime reports filed with the Baltimore Police Department. METHODS: Crime data were obtained from the Baltimore City Police Department from January 1, 2008 to March 31, 2013. Trauma data were obtained from a prospectively collected registry of all trauma patients presenting to Johns Hopkins Hospital from January 1, 2007 to March 31, 2013. Weather data were obtained from the National Climatic Data Center. Correlation coefficients were calculated and negative binomial regression was used to elucidate the independent associations of weather and temporal variables with the trauma and crime data. RESULTS: When adjusting for temporal and meteorological factors, maximum daily temperature was positively associated with total trauma, intentional injury, and gunshot wounds presenting to Johns Hopkins Hospital along with total crime, violent crime, and homicides in Baltimore City. Associations of average wind speed, daily precipitation, and daily snowfall with trauma and crime were far weaker and, when significant, nearly universally negative. CONCLUSION: Maximum daily temperature is the most important weather factor associated with violence and trauma in our study period and location. Our findings suggest potential implications for hospital staffing to be explored in future studies.

Critical role of non-muscle myosin light chain kinase in thrombin-induced endothelial cell inflammation and lung PMN infiltration.

The pathogenesis of acute lung injury (ALI) involves bidirectional cooperation and close interaction between inflammatory and coagulation pathways. A key molecule linking coagulation and inflammation is the procoagulant thrombin, a serine protease whose concentration is elevated in plasma and lavage fluids of patients with ALI and acute respiratory distress syndrome (ARDS). However, little is known about the mechanism by which thrombin contributes to lung inflammatory response. In this study, we developed a new mouse model that permits investigation of lung inflammation associated with intravascular coagulation. Using this mouse model and in vitro approaches, we addressed the role of non-muscle myosin light chain kinase (nmMLCK) in thrombin-induced endothelial cell (EC) inflammation and lung neutrophil (PMN) infiltration. Our in vitro experiments revealed a key role of nmMLCK in ICAM-1 expression by its ability to control nuclear translocation and transcriptional capacity of RelA/p65 in EC. When subjected to intraperitoneal thrombin challenge, wild type mice showed a marked increase in lung PMN infiltration via expression of ICAM-1. However, these responses were markedly attenuated in mice deficient in nmMLCK. These results provide mechanistic insight into lung inflammatory response associated with intravascular coagulation and identify nmMLCK as a critical target for modulation of lung inflammation.

Water consumption patterns and factors contributing to water consumption in arsenic affected population of rural West Bengal, India.

A direct water intake study was conducted for one year, involving 423 individuals from three arsenic (As) affected villages of West Bengal, India. Average direct water intake per person and per unit body weight was found to be 3.12±1.17 L/day and 78.07±47.08 mL/kg/day (± SD), respectively. Average direct water intakes for adult males, adult females and children (age <15 years) were 3.95, 3.03 and 2.14 L/day, respectively. Significant sex differentials were observed between ages 16-55 years. For all participants, a sharp increase in water intake up to 15 years of age was observed followed by a plateau at a higher intake level. Significant monthly, seasonal, regional, and occupational variability was also observed. Another study involving 413 subjects determined the amount of indirect water intake. Average indirect water intake per person was 1.80±0.64 L/day; for adult males, adult females and children, intake was 2.15, 1.81, and 1.10 L/day, respectively. Average total (direct + indirect) water intake was 4.92 L/person/day; for adult males, adult females and children, total intake was 6.10, 4.84, and 3.24 L/person/day, respectively. The overall contribution of indirect water intake to total water consumption was 36.6% for all participants. This study additionally elucidated several factors that contribute to variable water intake, which can lead to better risk characterization of subpopulations and water contaminant ingestion. The study reveals that the water intake rates in the three studied populations in West Bengal are greater than the assumed water intake rates utilized by the World Health Organization (WHO) in the establishment of drinking water quality guidelines; therefore, these assumed intake values may be inappropriate for the study population as well as similar ones.

Environmental arsenic contamination and its health effects in a historic gold mining area of the Mangalur greenstone belt of Northeastern Karnataka, India.

This report summarizes recent findings of environmental arsenic (As) contamination and the consequent health effects in a community located near historic gold mining activities in the Mangalur greenstone belt of Karnataka, India. Arsenic contents in water, hair, nail, soil and food were measured by FI-HG-AAS. Elemental analyses of soils were determined by ICP-MS (inductively coupled plasma-mass spectrometry). Of 59 tube-well water samples, 79% had As above 10 µg L(-1) (maximum 303 µg L(-1)). Of 12 topsoil samples, six were found to contain As greater than 2000 mg kg(-1) possibly indicating the impact of mine tailings on the area. All hair and nail samples collected from 171 residents contained elevated As. Arsenical skin lesions were observed among 58.6% of a total 181 screened individuals. Histopathological analysis of puncture biopsies of suspected arsenical dermatological symptoms confirmed the diagnosis in three out of four patients. Based on the time-course of As-like symptoms reported by the community as well as the presence of overt arsenicosis, it is hypothesized that the primary route of exposure in the study area was via contaminated groundwater; however, the identified high As content in residential soil could also be a significant source of As exposure via ingestion. Additional studies are required to determine the extent as well as the relative contribution of geologic and anthropogenic factors in environmental As contamination in the region. This study report is to our knowledge one of the first to describe overt arsenicosis in this region of Karnataka, India as well as more broadly an area with underlying greenstone geology and historic mining activity.

Status of groundwater arsenic contamination in Bangladesh: a 14-year study report.

Since 1996, 52,202 water samples from hand tubewells were analyzed for arsenic (As) by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS) from all 64 districts of Bangladesh; 27.2% and 42.1% of the tubewells had As above 50 and 10 µg/l, respectively; 7.5% contained As above 300 µg/l, the concentration predicting overt arsenical skin lesions. The groundwater of 50 districts contained As above the Bangladesh standard for As in drinking water (50 µg/l), and 59 districts had As above the WHO guideline value (10 µg/l). Water analyses from the four principal geomorphological regions of Bangladesh showed that hand tubewells of the Tableland and Hill tract regions are primarily free from As contamination, while the Flood plain and Deltaic region, including the Coastal region, are highly As-contaminated. Arsenic concentration was usually observed to decrease with increasing tubewell depth; however, 16% of tubewells deeper than 100 m, which is often considered to be a safe depth, contained As above 50 µg/l. In tubewells deeper than 350 m, As >50 µg/l has not been found. The estimated number of tubewells in 50 As-affected districts was 4.3 million. Based on the analysis of 52,202 hand tubewell water samples during the last 14 years, we estimate that around 36 million and 22 million people could be drinking As-contaminated water above 10 and 50 µg/l, respectively. However for roughly the last 5 years due to mitigation efforts by the government, non-governmental organizations and international aid agencies, many individuals living in these contaminated areas have been drinking As-safe water. From 50 contaminated districts with tubewell As concentrations >50 µg/l, 52% of sampled hand tubewells contained As <10 µg/l, and these tubewells could be utilized immediately as a source of safe water in these affected regions provided regular monitoring for temporal variation in As concentration. Even in the As-affected Flood plain, sampled tubewells from 22 thanas in 4 districts were almost entirely As-safe. In Bangladesh and West Bengal, India the crisis is not having too little water to satisfy our needs, it is the challenge of managing available water resources. The development of community-specific safe water sources coupled with local participation and education are required to slow the current effects of widespread As poisoning and to prevent this disaster from continuing to plague individuals in the future.