BACKGROUND: Arsenic is a common environmental toxin. Exposure to arsenic (particularly its inorganic form) through contaminated food and drinking water is an important public health burden worldwide, and is associated with increased risk of neurotoxicity, congenital anomalies, cancer, and adverse neurodevelopment in children. Arsenic is excreted following methylation reactions, which are mediated by folate. Provision of folate through folic acid supplements could facilitate arsenic methylation and excretion, thereby reducing arsenic toxicity. OBJECTIVES: To assess the effects of provision of folic acid (through fortified foods or supplements), alone or in combination with other nutrients, in lessening the burden of arsenic-related health outcomes and reducing arsenic toxicity in arsenic-exposed populations. SEARCH METHODS: In September 2020, we searched CENTRAL, MEDLINE, Embase, 10 other international databases, nine regional databases, and two trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing the provision of folic acid (at any dose or duration), alone or in combination with other nutrients or nutrient supplements, with no intervention, placebo, unfortified food, or the same nutrient or supplements without folic acid, in arsenic-exposed populations of all ages and genders. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two RCTs with 822 adults exposed to arsenic-contaminated drinking water in Bangladesh. The RCTs compared 400 µg/d (FA400) or 800 µg/d (FA800) folic acid supplements, given for 12 or 24 weeks, with placebo. One RCT, a multi-armed trial, compared FA400 plus creatine (3 g/d) to creatine alone. We judged both RCTs at low risk of bias in all domains. Due to differences in co-intervention, arsenic exposure, and participants' nutritional status, we could not conduct meta-analyses, and therefore, provide a narrative description of the data. Neither RCT reported on cancer, all-cause mortality, neurocognitive function, or congenital anomalies. Folic acid supplements alone versus placebo Blood arsenic. In arsenic-exposed individuals, FA likely reduces blood arsenic concentrations compared to placebo (2 studies, 536 participants; moderate-certainty evidence). For folate-deficient and folate-replete participants who received arsenic-removal water filters as a co-intervention, FA800 reduced blood arsenic levels more than placebo (percentage change (%change) in geometric mean (GM) FA800 -17.8%, 95% confidence intervals (CI) -25.0 to -9.8; placebo GM -9.5%, 95% CI -16.5 to -1.8; 1 study, 406 participants). In one study with 130 participants with low baseline plasma folate, FA400 reduced total blood arsenic (%change FA400 mean (M) -13.62%, standard error (SE) ± 2.87; placebo M -2.49%, SE ± 3.25), and monomethylarsonic acid (MMA) concentrations (%change FA400 M -22.24%, SE ± 2.86; placebo M -1.24%, SE ± 3.59) more than placebo. Inorganic arsenic (InAs) concentrations reduced in both groups (%change FA400 M -18.54%, SE ± 3.60; placebo M -10.61%, SE ± 3.38). There was little to no change in dimethylarsinic acid (DMA) in either group. Urinary arsenic. In arsenic-exposed individuals, FA likely reduces the proportion of total urinary arsenic excreted as InAs (%InAs) and MMA (%MMA) and increases the proportion excreted as DMA (%DMA) to a greater extent than placebo (2 studies, 546 participants; moderate-certainty evidence), suggesting that FA enhances arsenic methylation. In a mixed folate-deficient and folate-replete population (1 study, 352 participants) receiving arsenic-removal water filters as a co-intervention, groups receiving FA had a greater decrease in %InAs (within-person change FA400 M -0.09%, 95% CI -0.17 to -0.01; FA800 M -0.14%, 95% CI -0.21 to -0.06; placebo M 0.05%, 95% CI 0.00 to 0.10), a greater decrease in %MMA (within-person change FA400 M -1.80%, 95% CI -2.53 to -1.07; FA800 M -2.60%, 95% CI -3.35 to -1.85; placebo M 0.15%, 95% CI -0.37 to 0.68), and a greater increase in %DMA (within-person change FA400 M 3.25%, 95% CI 1.81 to 4.68; FA800 M 4.57%, 95% CI 3.20 to 5.95; placebo M -1.17%, 95% CI -2.18 to -0.17), compared to placebo. In 194 participants with low baseline plasma folate, FA reduced %InAs (%change FA400 M -0.31%, SE ± 0.04; placebo M -0.13%, SE ± 0.04) and %MMA (%change FA400 M -2.6%, SE ± 0.37; placebo M -0.71%, SE ± 0.43), and increased %DMA (%change FA400 M 5.9%, SE ± 0.82; placebo M 2.14%, SE ± 0.71), more than placebo. Plasma homocysteine: In arsenic-exposed individuals, FA400 likely reduces homocysteine concentrations to a greater extent than placebo (2 studies, 448 participants; moderate-certainty evidence), in the mixed folate-deficient and folate-replete population receiving arsenic-removal water filters as a co-intervention (%change in GM FA400 -23.4%, 95% CI -27.1 to -19.5; placebo -1.3%, 95% CI -5.3 to 3.1; 1 study, 254 participants), and participants with low baseline plasma folate (within-person change FA400 M -3.06 µmol/L, SE ± 3.51; placebo M -0.05 µmol/L, SE ± 4.31; 1 study, 194 participants). FA supplements plus other nutrient supplements versus nutrient supplements alone In arsenic-exposed individuals who received arsenic-removal water filters as a co-intervention, FA400 plus creatine may reduce blood arsenic concentrations more than creatine alone (%change in GM FA400 + creatine -14%, 95% CI -22.2 to -5.0; creatine -7.0%, 95% CI -14.8 to 1.5; 1 study, 204 participants; low-certainty evidence); may not change urinary arsenic methylation indices (FA400 + creatine: %InAs M 13.2%, SE ± 7.0; %MMA M 10.8, SE ± 4.1; %DMA M 76, SE ± 7.8; creatine: %InAs M 14.8, SE ± 5.5; %MMA M 12.8, SE ± 4.0; %DMA M 72.4, SE ±7.6; 1 study, 190 participants; low-certainty evidence); and may reduce homocysteine concentrations to a greater extent (%change in GM FA400 + creatinine -21%, 95% CI -25.2 to -16.4; creatine -4.3%, 95% CI -9.0 to 0.7; 1 study, 204 participants; low-certainty evidence) than creatine alone. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that FA supplements may benefit blood arsenic concentration, urinary arsenic methylation profiles, and plasma homocysteine concentration versus placebo. There is low-certainty evidence that FA supplements plus other nutrients may benefit blood arsenic and plasma homocysteine concentrations versus nutrients alone. No studies reported on cancer, all-cause mortality, neurocognitive function, or congenital anomalies. Given the limited number of RCTs, more studies conducted in diverse settings are needed to assess the effects of FA on arsenic-related health outcomes and arsenic toxicity in arsenic-exposed adults and children.

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

Reactivation of Chagas disease has been described in immunosuppressed patients, but there is a paucity of literature describing reactivation in patients on immunosuppressive therapies for the treatment of autoimmune rheumatic diseases. We describe a case of Chagas disease reactivation in a woman taking azathioprine and prednisone for limited cutaneous systemic sclerosis (lcSSc). Reactivation manifested as indurated and erythematous cutaneous nodules. Sequencing of a skin biopsy specimen confirmed the diagnosis of Chagas disease. She was treated with benznidazole with clinical improvement in the cutaneous lesions. However, her clinical course was complicated and included disseminated CMV disease and subsequent septic shock due to bacteremia. Our case and review of the literature highlight that screening for Chagas disease should be strongly considered for patients who will undergo immunosuppression for treatment of autoimmune disease if epidemiologically indicated.

Society needs critical nursing services around the clock and, as a result, nurses often work shift work and long work hours (SWLWH). These hours can prevent nurses from getting the seven or more hours of quality sleep each day that experts recommend (Watson, et al., 2015). Nurses on SWLWH are at risk for cardiovascular disease, gastrointestinal and psychological disorders, cancer, type 2 diabetes, injuries, musculoskeletal disorders, all-cause mortality, adverse reproductive outcomes, and difficulty managing chronic diseases (Caruso, et al., 2017; Caruso & Waters, 2008; Gan, et al. 2015; Gu, et al., 2015; DHHS, 2018; IARC Monographs Vol 124 Group, 2019; NIOSH, et al., 2015; Ramin, et al., 2014; Torquati, et al., 2017). Furthermore, tired nurses are at risk for making patient care errors and drowsy driving crashes (Bae & Fabry, 2014; Ftouni, et al., 2013; Geiger-Brown, et al., 2012; Geiger-Brown & Trinkoff, 2010; Lee, et al., 2016; Trinkoff, et al., 2011). The presence of SWLWH is also related to retention issues, including nurses expressing intention-to-leave or quitting the job (Hayes, et al., 2012; Moloney, et al., 2018). These conditions also have contributed to nursing shortages in certain specialties and practice locations (Marć, et al., 2018 ). Shortages are a grave concern, as the population is aging and the need for nurses is projected to strongly increase (Auerbach, Buerhaus, & Staiger, 2017). Thus, interventions to reduce nursing fatigue are sorely needed. The American Academy of Nursing (the Academy) supports efforts to reduce fatigue in nurses through education, workplace policies and management systems, and fatigue countermeasures. The Academy recommends that healthcare services and standard-setting organizations establish policies to address this pervasive workplace hazard, thereby promoting nurses’ health and safety along with patient and public safety.

Background: ME/CFS is a complex and disabling illness with substantial economic burden and functional impairment comparable to heart disease and multiple sclerosis. Many patients with ME/CFS do not receive appropriate healthcare, partially due to lack of diagnostic tests, and knowledge/attitudes/beliefs about ME/CFS. This study was to assess the utility of US ambulatory healthcare data in profiling demographics, co-morbidities, and healthcare in ME/CFS. Methods: Data came from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) in the U.S. Weighted analysis was performed. We examined 9.06 billion adult visits from 2000 to 2009 NAMCS/NHAMCS data. ME/CFS-related visits were identified by ICD-9-CM code, 780.71, up to tertiary diagnosis. Results: We estimated 2.9 million (95% CI: 1.8-3.9 million) ME/CFS-related visits during 2000-2009, with no statistical evidence (p-trend = 0.31) for a decline or increase in ME/CFS-related visits. Internists, general and family practitioners combined provided 52.12% of these visits. Patients with ME/CFS-related visits were mostly in their 40 and 50 s (47.76%), female (66.07%), white (86.95%), metropolitan/urban residents (92.05%), and insured (87.26%). About 71% of ME/CFS patients had co-morbidities, including depression (35.79%), hypertension (31.14%), diabetes (20.30%), and arthritis (14.11%). As one quality indicator, physicians spent more time on ME/CFS-related visits than non-ME/CFS visits (23.62 vs. 19.38 min, p = 0.065). As additional quality indicators, the top three preventive counseling services provided to patients with ME/CFS-related visits were diet/nutrition (8.33%), exercise (8.21%), and smoking cessation (7.24%). Compared to non-ME/CFS visits, fewer ME/CFS-related visits included counseling for stress management (0.75 vs. 3.14%, p = 0.010), weight reduction (0.88 vs. 4.02%, p = 0.002), injury prevention (0.04 vs. 1.64%, p < 0.001), and family planning/contraception (0.17 vs. 1.45%, p = 0.037). Conclusions: Visits coded with ME/CFS did not increase from 2000 to 2009. Almost three quarters of ME/CFS-related visits were made by ME/CFS patients with other co-morbid conditions, further adding to complexity in ME/CFS healthcare. While physicians spent more time with ME/CFS patients, a lower proportion of ME/CFS patients received preventive counseling for weight reduction, stress management, and injury prevention than other patients despite the complexity of ME/CFS. NAMCS/NHAMCS data are useful in evaluating co-morbidities, healthcare utilization, and quality indicators for healthcare in ME/CFS.

The American Academy of Nursing promotes management practices in health care organizations and | strategies in the nurse’s personal life to support sleep | health in nurses and, as a result, an alert nursing | workforce fit to perform their jobs and more able to live | healthy lives. Society requires critical nursing services | around the clock. Consequently, shift work and long | work hours are common in health care organizations | and negatively affect a significant percent of nurses. | Working at night and irregular hours compromise | human physiology dictated by the need for sleep and | circadian rhythms. The challenge that nurses on shift | work face is the need to work at night (when our | physiology promotes sleep) and sleep during the day | (when our physiology promotes activity). When shift | work combines with long work hours (e.g., shifts of | 12 hr or more) and leads to sleep deficiency or disruption to circadian rhythms, the health and safety costs | of this conflict with human physiology are potentially | significant. Sleep deficiency is a broad term that includes inadequate sleep duration, poor sleep quality, | untreated sleep disorders, and mistimed sleep that is | not synchronized with circadian rhythms. Sleep deficiency can affect nurses’ work readiness and health, | safety, and well-being. Evidence is building that long | shifts, shift rotations, double shifts, evening, and night | shifts are associated with multiple short- and longterm health and safety risks to the nurse (National | Institute for Occupational Safety and Health [NIOSH]; | NIOSH, Caruso, Geiger-Brown, Takahashi, Trinkoff, & | Nakata, 2015). Tired nurses are also at risk for making | fatigue-related patient care errors that can endanger | their patients (Bae & Fabry, 2014). These risks also | extend to the nurse’s family, their employer/health | care organization, and the broader society when tired | nurses make errors at work and home or crash their vehicle due to drowsy driving. This complex hazard | requires a variety of personal, workplace, and public | health strategies to reduce these risks. Unfortunately, | persons working in health care organizations may not | fully understand the health and safety risks that are | associated with fatigue and may be unaware of | evidence-based strategies to reduce these risks. Yet | evidence shows that it is possible to limit or modify the | adverse impact of shift work and long work hours on | nurses by improving their sleep and reducing fatigue.

Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.

Fetal hemoglobin (HbF) protects against many but not all of the hematologic and clinical complications of sickle cell anemia.1,2 This protection is dependent on the ability of HbF to hinder deoxyHbS polymerization. HbF level is variable and highly heritable. Previous genetic association studies found single nucleotide polymorphisms (SNPs) in regions of BCL11A (chromosome 2p), in the HBS1L-MYB intergenic polymorphism (HMIP; chromosome 6q), and linked to HBB (chromosome 11p) that were associated with HbF (reviewed in Akinsheye et al1). Our aim was to perform a meta-analysis of genome-wide association studies (GWAS) to find genetic loci with modest effect sizes that were associated with HbF when a larger sample size was examined. | Common SNPs (585, 563 total) from 7 cohorts totaling 2040 patients were meta-analyzed using the software Meta Analysis Helper (METAL)3 with inverse variance method, where effect estimates are weighted in proportion to their precisions.4 The 7 cohorts included in the meta-analysis are: Cooperative Study of Sickle Cell Disease (CSSCD: n = 841), Multicenter Study of Hydroxyurea (MSH: n = 178), Pulmonary Hypertension and the Hypoxic Response in Sickle Cell Disease (PUSH) study (n = 73), Comprehensive Sickle Cell Centers Collaborative Data (C-data) project (n = 127), Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Treatment (Walk-PHaSST) trial (n = 181), Duke University Outcome Modifying Genes study (n = 152), and Silent Infarct Transfusion (SIT) trial (n = 488).

BACKGROUND: The health impacts of pulmonary impairment after tuberculosis (TB) treatment have not been included in assessments of TB burden. Therefore, previous global and national TB burden estimates do not reflect the full consequences of surviving TB. We assessed the burden of TB including pulmonary impairment after tuberculosis in Tarrant County, Texas using Disability-adjusted Life Years (DALYs) METHODS: TB burden was calculated for all culture-confirmed TB patients treated at Tarrant County Public Health between January 2005 and December 2006 using identical methods and life tables as the Global Burden of Disease Study. Years of life-lost were calculated as the difference between life expectancy using standardized life tables and age-at-death from TB. Years lived-with-disability were calculated from age and gender-specific TB disease incidence using published disability weights. Non-fatal health impacts of TB were divided into years lived-with-disability-acute and years lived-with-disability-chronic. Years lived-with-disability-acute was defined as TB burden resulting from illness prior to completion of treatment including the burden from treatment-related side effects. Years lived-with-disability-chronic was defined as TB burden from disability resulting from pulmonary impairment after tuberculosis. RESULTS: There were 224 TB cases in the time period, of these 177 were culture confirmed. These 177 subjects lost a total of 1189 DALYs. Of these 1189 DALYs 23% were from years of life-lost, 2% were from years lived-with-disability-acute and 75% were from years lived-with-disability-chronic. CONCLUSIONS: Our findings demonstrate that the disease burden from TB is greater than previously estimated. Pulmonary impairment after tuberculosis was responsible for the majority of the burden. These data demonstrate that successful TB control efforts may reduce the health burden more than previously recognized.