Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

High Fluctuation Between Anticoagulants,Frequent Off-Label Dosing,and No Difference Concerning Outcomes: Results of a Real-Life Cohort Study

BackgroundRecently published studies indicated a high proportion of patients taking direct oral anticoagulants (DOACs) are off-label under- or overdosed. The present study aimed at investigating whether off-label dosages are corrected over time and whether off-label doses are associated with differences in bleeding rates, ischemic stroke, or venous thromboembolism.MethodsIn this retrospective cohort study, patients presenting to our emergency department between January 1 and December 31, 2018, with therapeutic oral anticoagulation were included (ie, vitamin-K antagonists [VKAs], rivaroxaban, apixaban, edoxaban, and dabigatran) and follow-up for a maximum of 2 years until December 31, 2019, was made. Detailed chart reviews were performed for each case concerning characteristics, indication, bleeding complications, or changes in the used substance or dosage.ResultsWe reviewed 2588 consultations of 1228 patients receiving therapeutic oral anticoagulation. During the maximum follow-up period of 2 years vitamin K antagonists and rivaroxaban lost the largest proportions in favor of apixaban. The overall distribution of dosage correctness remained almost unimproved (correct dosing in 62.5%, underdosing in 23.6%, coverdosing in 13.9%).The corresponding outcomes did not differ with respect to bleeding events, ischemic stroke, or venous thromboembolism among various anticoagulants as well as between correct and off-label doses.ConclusionsA rising proportion of existing oral anticoagulation regimes was changed to apixaban, while the proportion of off-label dosages of all oral anticoagulants remained stable. No difference in bleeding rates, de novo strokes, or thromboembolisms was found between anticoagulants as well as between correct and off-label doses.     

The human gut microbiome and health inequities

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host–gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.     

Reductions in NO2 burden over north equatorial Africa from decline in biomass burning in spite of growing fossil fuel use, 2005 to 2017

Socioeconomic development in low- and middle-income countries has been accompanied by increased emissions of air pollutants, such as nitrogen oxides [NO_x: nitrogen dioxide (NO₂) + nitric oxide (NO)], which affect human health. In sub-Saharan Africa, fossil fuel combustion has nearly doubled since 2000. At the same time, landscape biomass burning—another important NO_x source—has declined in north equatorial Africa, attributed to changes in climate and anthropogenic fire management. Here, we use satellite observations of tropospheric NO₂ vertical column densities (VCDs) and burned area to identify NO₂ trends and drivers over Africa. Across the northern ecosystems where biomass burning occurs—home to hundreds of millions of people—mean annual tropospheric NO₂ VCDs decreased by 4.5% from 2005 through 2017 during the dry season of November through February. Reductions in burned area explained the majority of variation in NO₂ VCDs, though changes in fossil fuel emissions also explained some variation. Over Africa’s biomass burning regions, raising mean GDP density (USD⋅km⁻²) above its lowest levels is associated with lower NO₂ VCDs during the dry season, suggesting that economic development mitigates net NO₂ emissions during these highly polluted months. In contrast to the traditional notion that socioeconomic development increases air pollutant concentrations in low- and middle-income nations, our results suggest that countries in Africa’s northern biomass-burning region are following a different pathway during the fire season, resulting in potential air quality benefits. However, these benefits may be lost with increasing fossil fuel use and are absent during the rainy season.

Socioeconomic development and population growth in low- and middle-income countries have been widely associated with increased environmental degradation, including rapid increases in emissions of air pollutants (1–3). In contrast, in countries with a high per capita gross domestic product (GDP), various socioeconomic, institutional, and regulatory factors often cause economic growth to be accompanied by reductions of some pollutant emissions, though these emissions may simply be outsourced to lower income countries (4). The relationship between income level and environmental pressure—known as the Environmental Kuznets Curve—has often been conceptualized as an inverted U-shaped curve, but a wide array of functional relationships is possible (3). For emissions of air pollutants, the relationship has generally been described as an inverted U-shaped curve, though carbon dioxide generally does not follow such a curve (3, 5). Some researchers argue that low- and middle-income countries can mitigate or shorten the period of rapid emissions growth that tends to accompany socioeconomic development for at least some pollutants (4). Africa, and sub-Saharan Africa in particular, is characterized by countries with low but growing per capita GDP and rapid population growth, which have been linked to increases in emissions of carbon dioxide and particulate matter (6). As these countries continue their trajectories of economic development, emissions of air pollutants from fossil fuel and biofuel combustion are expected to experience explosive growth (7).Nitrogen dioxide (NO₂) is a reactive gas and air pollutant with a lifetime in the atmosphere on the order of hours (8). In the atmosphere, NO₂ interconverts rapidly with nitric oxide (NO), and the two species are collectively referred to as NO_x. NO₂ itself is toxic, is regulated by the US Environmental Protection Agency, and has been associated with premature mortality and asthma [though its direct effects on health are not clear (9) and it may instead function as a proxy for other pollutants, such as ozone and aerosols that have direct health and mortality impacts (10)]. NO_x is also a key precursor to the formation of tropospheric ozone (O₃), which is damaging to both crop productivity and human health; anthropogenic O₃ contributes to roughly half a million premature deaths annually, of which nearly 20,000 are in Africa (11). In addition, NO_x is involved in reactions with atmospheric ammonia (NH₃) to form nitrate aerosols, which contribute to particulate matter pollution (12) as well as in reactions with volatile organic compounds (VOCs), which form organic nitrates (13). Because of the short lifetime of NO₂, and because it can function as an indicator for other pollutants, it can serve as an indicator of overall changes in air quality.NO and NO₂ are emitted from a variety of natural and anthropogenic sources. Fossil fuel combustion and anthropogenic alterations to soils through fertilization or livestock management are the primary sources of NO_x in many parts of the world. In sub-Saharan Africa (excluding South Africa), fossil fuel combustion and fertilizer use has been considerably lower than elsewhere, and natural soils and biomass burning have historically been more important sources (14). This is true even in Nigeria (15), which experiences substantial emissions of VOCs from the oil and gas industry (16). NO_x emissions from Lagos have been shown to be either lower than (15) or comparable to other megacities (17), and NO₂ concentrations are generally low during the rainy season, but air quality can become heavily degraded during the biomass burning season (15, 18). However, fossil fuel combustion in the region nearly doubled between 2000 and 2016 (19) and associated emissions of NO_x are projected to increase sixfold by 2030 in the absence of regulation, as compared to 2005 levels (7).This increase in fossil fuel combustion is occurring against the backdrop of Africa’s unique, fire-prone savanna ecosystems, home to 70% of the global area burned each year (20). Biomass burning in Africa is estimated to be responsible for NO_x emissions of roughly 4 Tg N⋅yr⁻¹, equivalent to about half of all NO_x emissions for the continent (21), and one third to half of NO_x emissions from biomass burning globally (21–23). The majority of biomass burning in Africa occurs in northern and southern bands of savanna, savanna-forest mosaic, and woodland ecoregions, with a seasonality that follows the migration of the intertropical convergence zone.The early part of the 21st century has been accompanied by a global decline in burned area, with some of the largest declines occurring in Africa’s northern fire band (24). Some of the burned area decline in the northern fire band can be attributed to changes in precipitation that, in turn, affect the quantity and moisture content of available fuels (24–26). However, active anthropogenic suppression of fire has also played an important role (24, 25). Burning is thought to be used as a management strategy—among other uses, humans ignite fires to mineralize nutrients, improve grazing, and reduce fuel loads and the potential for large, uncontrolled fires (27). Increased population density and the introduction of agricultural land into African savanna landscapes—reflecting socioeconomic transitions from traditional nomadic pastoralist lifestyles (28)—have been associated with a sharp decrease in burned area as people either reduce ignition or suppress fires to protect villages and farms, with a reduction in the amount of pasture area to be maintained (25).Unfortunately, sub-Saharan Africa remains a severely understudied region—for example, agricultural soil NO fluxes have only been measured directly for two sites (29, 30), and surface air quality monitoring is extremely limited compared to other parts of the world (31). Remote sensing products provide an important tool for filling some of these data gaps. The short NO₂ lifetime in the planetary boundary layer makes it possible to use satellite observations to directly evaluate emissions sources, especially in regions with high temperatures, which tend to shorten the NO₂ lifetime, and in relatively polluted regions, where total column densities and surface emissions are highly correlated (ref. 8 and references therein). Although recent remote sensing work has evaluated long-term trends in NO₂ concentrations around the world, recent trends in the biomass burning region of northern Africa have not been explicitly evaluated, and the relative impacts of socioeconomic development—the possibility of reduced NO_x emissions because of anthropogenic fire suppression and of increasing NO_x emissions from growing fossil fuel use—remain unknown. In general, studies on global trends in NO₂ tend not to focus on Africa, likely because the regions with the highest NO₂ concentrations are in China, Europe, and the United States (e.g., refs. 1, 21). Some earlier studies observed a decline in NO₂ VCDs over north equatorial Africa (32, 33), but others did not (34). These and other large-scale studies (e.g., refs. 8, 34, 35) did not identify mechanisms for the observed NO₂ dynamics, but rather focused on understanding anthropogenic influences on trends in other regions.Indoor air pollution from biomass combustion for fuel is an important health concern (36). We do not focus on this source. Biofuel combustion is responsible for emissions of 0.6 Tg NO annually across all of Africa (37), which is less than 10% of the magnitude of landscape biomass burning emissions estimated by the Global Fire Emissions Database version 4s [GFED4s (38)] and represents a much smaller proportion of NO_x emissions from landscape biomass burning regions during the dry season.Here, we use observations of NO₂ by the Ozone Monitoring Instrument [OMI (39)] and burned area from the Moderate Resolution Imaging Spectroradiometer [MODIS (40)] to demonstrate that the recent decline in burned area in the productive savannas of north equatorial Africa—home to over 275 million people—is associated with large declines in tropospheric NO₂ VCDs during the biomass burning season from 2005 through 2017, though positive trends explained in part by increasing fossil fuel combustion were observed in other seasons, especially over Nigeria.     

Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.      

Impact of a Letter-Grade Program on Restaurant Sanitary Conditions and Diner Behavior in New York City

Objectives. We evaluated the impact of the New York City restaurant letter-grading program on restaurant hygiene, food safety practices, and public awareness.Methods. We analyzed data from 43 448 restaurants inspected between 2007 and 2013 to measure changes in inspection score and violation citations since program launch in July 2010. We used binomial regression to assess probability of scoring 0 to 13 points (A-range score). Two population-based random-digit-dial telephone surveys assessed public perceptions of the program.Results. After we controlled for repeated restaurant observations, season of inspection, and chain restaurant status, the probability of scoring 0 to 13 points on an unannounced inspection increased 35% (95% confidence interval [CI] = 31%, 40%) 3 years after compared with 3 years before grading. There were notable improvements in compliance with some specific requirements, including having a certified kitchen manager on site and being pest-free. More than 91% (95% CI = 88%, 94%) of New Yorkers approved of the program and 88% (95% CI = 85%, 92%) considered grades in dining decisions in 2012.Conclusions. Restaurant letter grading in New York City has resulted in improved sanitary conditions on unannounced inspection, suggesting that the program is an effective regulatory tool.Restaurant food safety is increasingly important, with almost half of the US food dollar spent on restaurant food1 and about one third of caloric intake from foods prepared outside the home.2 In New York City (NYC), residents eat out nearly 1 billion times each year.3 Although most diners do not get sick, foodborne pathogens cause millions of preventable illnesses in the United States annually.4 The exact proportion of restaurant-attributable foodborne illness is unknown, but national surveillance in the United States found that two thirds of reported foodborne outbreaks from 1998 through 2008 occurred in the restaurant or deli setting,5 and consumption of food prepared outside the home has been linked to an increased risk of sporadic foodborne diseases.6Regular inspection of restaurants for food safety is a core function of local health authorities, guided by the US Food and Drug Administration (FDA) Food Code.7 Although all states have sanitation codes modeled after the FDA Food Code,8 implementation methods vary by jurisdiction. The NYC Department of Health and Mental Hygiene (hereafter, Health Department) is charged with inspecting restaurants, coffee shops, bars, nightclubs, employee or university cafeterias, bakeries, and fixed-site food stands (hereafter, restaurants). Its inspection program uses a scoring system to measure compliance with the NYC Health Code, which is updated regularly to maintain consistency with the FDA Food Code and the New York State Sanitary Code. Restaurants are entitled to an impartial review of inspection results by an administrative tribunal, which can improve an assigned score and reduce associated monetary fines.Before letter grading, the Health Department aimed to inspect restaurants at least once per year and imposed monetary fines for violations cited at inspections. Inspection results were available on the Health Department Web site. However, financial disincentives and the Web site posting were insufficient to drive improvements across the industry, with most restaurants cited for multiple public health hazards. Mean inspection scores and restaurant sanitary conditions were stagnant (D. Kass, email communication, February 2009).In an effort to improve restaurant food safety and increase transparency of inspection information, the Health Department launched its letter-grade program on July 27, 2010. The program uses public disclosure of inspection scores in the form of letter grades at point of decision-making; a more finely tuned, risk-based inspection schedule; and financial incentives to encourage high food-safety standards. It began after an 18-month planning process that included a public announcement of the intent to begin letter grading; meetings with restaurant industry representatives, food safety experts, and regulators from a jurisdiction with a restaurant sanitary grade program; promulgation of 2 regulations subject to notice and comment; and training and education for restaurateurs. The process was covered by the media, and by July 2010, restaurateurs were aware of the program and anticipating the launch.9,10We evaluated the impact of the restaurant letter-grade program by assessing (1) hygiene and food-safety practices as characterized by inspection outcomes before and after program implementation and (2) public response to the program measured by 2 population-based telephone surveys.