Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation.
...To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation.
An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711).
Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa.
1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection.
Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring.
The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event-monitoring devices for self-administration. The main secondary outcome was adverse events.
Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration-with-reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups.
Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically.
These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible.
Centers for Disease Control and Prevention.
Rising atmospheric carbon dioxide (CO2), primarily from human fossil fuel combustion, reduces ocean pH and causes wholesale shifts in seawater carbonate chemistry. The process of ocean acidification ...is well documented in field data, and the rate will accelerate over this century unless future CO2 emissions are curbed dramatically. Acidification alters seawater chemical speciation and biogeochemical cycles of many elements and compounds. One well-known effect is the lowering of calcium carbonate saturation states, which impacts shell-forming marine organisms from plankton to benthic molluscs, echinoderms, and corals. Many calcifying species exhibit reduced calcification and growth rates in laboratory experiments under high-CO2 conditions. Ocean acidification also causes an increase in carbon fixation rates in some photosynthetic organisms (both calcifying and noncalcifying). The potential for marine organisms to adapt to increasing CO2 and broader implications for ocean ecosystems are not well known; both are high priorities for future research. Although ocean pH has varied in the geological past, paleo-events may be only imperfect analogs to current conditions.
Children and youth with special health care needs (CYSHCN) and their families continue to face challenges in accessing health care and other services in an integrated, family-centered, ...evidence-informed, culturally responsive system. More than 12 million, or almost 86%, of CYSHCN ages 1-17 years do not have access to a well-functioning system of services. Further, the inequities experienced by CYSHCN and their families, particularly those in under-resourced communities, highlight the critical need to address social determinants of health and our nation's approach to delivering health care. To advance the system and prioritize well-being and optimal health for CYSHCN, the Health Resources and Services Administration's Maternal and Child Health Bureau, with input from diverse stakeholders, developed a set of core principles and actionable strategies for the field. This article presents principles and strategies in the Blueprint for Change: Guiding Principles for a System of Services for CYSHCN and Their Families (Blueprint for Change), which acknowledges the comprehensive needs of CYSHCN, a changing health care system, and the disparities experienced by many CYSHCN. Four critical areas drive the Blueprint for Change: health equity, family and child well-being and quality of life, access to services, and financing of services. Although discussed separately, these critical areas are inherently interconnected and intend to move the field forward at the community, state, and federal levels. Addressing these critical areas requires a concerted, holistic, and integrated approach that will help us achieve the goal that CYSHCN enjoy a full life from childhood through adulthood and thrive in a system that supports their families and their social, health, and emotional needs, ensuring their dignity, autonomy, independence, and active participation in their communities.
Abstract
Background
Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug ...reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP.
Methods
We analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated.
Results
Among 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19–3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19–3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15–4.42).
Conclusions
Although most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve.
Clinical Trials Registration. NCT01582711.
We found that patients commonly reported symptoms while receiving 3-month daily rifapentine plus isoniazid for latent tuberculosis infection, which were typically mild and resolved on their own. Systemic drug reactions occurred but did not always lead to discontinuation of treatment.
CONTEXT Noninvasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. In some countries this testing has ...transitioned to clinical care, despite the absence of a formal assessment of performance. OBJECTIVE To document overall test performance of noninvasive fetal sex determination using cell-free fetal DNA and to identify variables that affect performance. DATA SOURCES Systematic review and meta-analysis with search of PubMed (January 1, 1997-April 17, 2011) to identify English-language human studies reporting primary data. References from review articles were also searched. STUDY SELECTION AND DATA EXTRACTION Abstracts were read independently to identify studies reporting primary data suitable for analysis. Covariates included publication year, sample type, DNA amplification methodology, Y chromosome sequence, and gestational age. Data were independently extracted by 2 reviewers. RESULTS From 57 selected studies, 80 data sets (representing 3524 male-bearing pregnancies and 3017 female-bearing pregnancies) were analyzed. Overall performance of the test to detect Y chromosome sequences had the following characteristics: sensitivity, 95.4% (95% confidence interval CI, 94.7%-96.1%) and specificity, 98.6% (95% CI, 98.1%-99.0%); diagnostic odds ratio (OR), 885; positive predictive value, 98.8%; negative predictive value, 94.8%; area under curve (AUC), 0.993 (95% CI, 0.989-0.995), with significant interstudy heterogeneity. DNA methodology and gestational age had the largest effects on test performance. Methodology test characteristics were AUC, 0.988 (95% CI, 0.979-0.993) for polymerase chain reaction (PCR) and AUC, 0.996 (95% CI, 0.993-0.998) for real-time quantitative PCR (RTQ-PCR) (P = .02). Gestational age test characteristics were AUC, 0.989 (95% CI, 0.965-0.998) (<7 weeks); AUC, 0.994 (95% CI, 0.987-0.997) (7-12 weeks); AUC, 0.992 (95% CI, 0.983-0.996) (13-20 weeks); and AUC, 0.998 (95% CI, 0.990-0.999) (>20 weeks) (P = .02 for comparison of diagnostic ORs across age ranges). RTQ-PCR (sensitivity, 96.0%; specificity, 99.0%) outperformed conventional PCR (sensitivity, 94.0%; specificity, 97.3%). Testing after 20 weeks (sensitivity, 99.0%; specificity, 99.6%) outperformed testing prior to 7 weeks (sensitivity, 74.5%; specificity, 99.1%), testing at 7 through 12 weeks (sensitivity, 94.8%; specificity, 98.9%), and 13 through 20 weeks (sensitivity, 95.5%; specificity, 99.1%). CONCLUSIONS Despite interstudy variability, performance was high using maternal blood. Sensitivity and specificity for detection of Y chromosome sequences was greatest using RTQ-PCR after 20 weeks' gestation. Tests using urine and tests performed before 7 weeks' gestation were unreliable.
Recent studies have proposed that millennial-scale reorganization of the ocean-atmosphere circulation drives increased upwelling in the Southern Ocean, leading to rising atmospheric carbon dioxide ...levels and ice age terminations. Southward migration of the global monsoon is thought to link the hemispheres during deglaciation, but vital evidence from the southern sector of the vast Australasian monsoon system is yet to emerge. Here we present a 230thorium-dated stalagmite oxygen isotope record of millennial-scale changes in Australian-Indonesian monsoon rainfall over the last 31,000 years. The record shows that abrupt southward shifts of the Australian-Indonesian monsoon were synchronous with North Atlantic cold intervals 17,600-11,500 years ago. The most prominent southward shift occurred in lock-step with Heinrich Stadial 1 (17,600-14,600 years ago), and rising atmospheric carbon dioxide. Our findings show that millennial-scale climate change was transmitted rapidly across Australasia and lend support to the idea that the 3,000-year-long Heinrich 1 interval could have been critical in driving the last deglaciation.
Several studies have evaluated whether the distribution of natural environments differs between marginalized and privileged neighborhoods. However, most studies restricted their analyses to a single ...or handful of cities and used different natural environment measures.
We evaluated whether natural environments are inequitably distributed based on socioeconomic status (SES) and race/ethnicity in the contiguous United States.
We obtained SES and race/ethnicity data (2015-2019) for all U.S. Census tracts. For each tract, we calculated the Normalized Different Vegetation Index (NDVI) for 2020, NatureScore (a proprietary measure of the quantity and quality of natural elements) for 2019, park cover for 2020, and blue space for 1984-2018. We used generalized additive models with adjustment for potential confounders and spatial autocorrelation to evaluate associations of SES and race/ethnicity with NDVI, NatureScore, park cover, and odds of containing blue space in all tracts (
) and in urban tracts (
). To compare effect estimates, we standardized NDVI, NatureScore, and park cover so that beta coefficients presented a percentage increase or decrease of the standard deviation (SD).
Tracts with higher SES had higher NDVI, NatureScore, park cover, and odds of containing blue space. For example, urban tracts in the highest median household income quintile had higher NDVI 44.8% of the SD (95% CI: 42.8, 46.8) and park cover 16.2% of the SD (95% CI: 13.5, 19.0) compared with urban tracts in the lowest median household income quintile. Across all tracts, a lower percentage of non-Hispanic White individuals and a higher percentage of Hispanic individuals were associated with lower NDVI and NatureScore. In urban tracts, we observed weak positive associations between percentage non-Hispanic Black and NDVI, NatureScore, and park cover; we did not find any clear associations for percentage Hispanics.
Multiple facets of the natural environment are inequitably distributed in the contiguous United States. https://doi.org/10.1289/EHP11164.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Introduction: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic ...medical conditions is limited.
Methods: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB.
Findings: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI 1.4, 1.9), PTB (aRR 1.4, 95% CI 1.3, 1.4), and early term birth (aRR 1.1, 95% CI 1.1, 1.2). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity.
Interpretation: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons.
Funding: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) K12 HD052163 and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.
PDF
