Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection.

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.

Effects of Sea Salt Aerosol Emissions for Marine Cloud Brightening on Atmospheric Chemistry: Implications for Radiative Forcing.

Marine cloud brightening (MCB) is proposed to offset global warming by emitting sea salt aerosols to the tropical marine boundary layer, which increases aerosol and cloud albedo. Sea salt aerosol is the main source of tropospheric reactive chlorine (Cl y ) and bromine (Br y ). The effects of additional sea salt on atmospheric chemistry have not been explored. We simulate sea salt aerosol injections for MCB under two scenarios (212-569 Tg/a) in the GEOS-Chem global chemical transport model, only considering their impacts as a halogen source. Globally, tropospheric Cl y and Br y increase (20-40%), leading to decreased ozone (-3 to -6%). Consequently, OH decreases (-3 to -5%), which increases the methane lifetime (3-6%). Our results suggest that the chemistry of the additional sea salt leads to minor total radiative forcing compared to that of the sea salt aerosol itself (~2%) but may have potential implications for surface ozone pollution in tropical coastal regions.

Validity of electrical impedance myography to estimate percent body fat: comparison to bio-electrical impedance and dual-energy X-ray absorptiometry.

BACKGROUND: Assessment of percent body fat (%BF) is typically measured with bioelectrical impedance (BIA) as a proxy for dual-energy X-ray absorptiometry (DXA). Notably, poorer agreement between BIA and DXA among persons who are overweight or obese has been reported. The use of electrical impedance myography (EIM) as a proxy for DXA has not been validated. The objective was to evaluate an EIM device and two multi-frequency BIA devices with the reference standard (DXA) stratified by weight status and gender. METHODS: In a convenience sample of 82 adults, %BF assessed by EIM and two BIA devices was compared to DXA. Agreement between devices was tested with intra-class correlation coefficients (ICC) and Bland-Altman plots. RESULTS: Agreement between DXA and EIM (ICC=0.77) was poorer than the agreement between either BIA device with DXA (ICC>0.87). Stratified by sex, agreement between EIM and DXA was greater for men than women (ICC=0.81 and ICC=0.61, respectively). Stratified by BMI, agreement between EIM and DXA was best for normal-weight individuals (ICC=0.89) and progressively poorer for overweight (ICC=0.80) and obese (ICC=0.67) individuals. Bland-Altman plots revealed wide limits of agreement and an increase in EIM mean difference as average %BF increased. Similar trends were seen in BIA assessments. CONCLUSIONS: EIM and BIA substantially underestimate %BF in overweight and obese individuals. Wide limits of agreement coupled with variable ICC limit device interchangeability with one another and limit clinical utility.

Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial.

Background: 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. Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design: 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). Setting: Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants: 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention: 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. Measurements: 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. Results: 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. Limitation: Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically. Conclusion: 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. Primary Funding Source: Centers for Disease Control and Prevention.

Relevance of Uterine Subseptations: What Length Should Warrant Hysteroscopic Resection?

OBJECTIVES: Existing recommendations warrant correction of uterine subseptations longer than 10 mm. We assessed whether a different subseptation length is indicated for intervention by evaluating the postoperative decrease in cavity width. METHODS: We conducted a prospective controlled cohort study at a university center. Healthy women and women with subseptations were evaluated with three-dimensional ultrasound before and after undergoing surgical resection of uterine subseptations by hysteroscopy. Measurement of the subseptum's length and width, and total cavity width, were obtained in both groups of women. We created a receiver operating characteristic curve using 7-mm cavity postoperative width change as the reference variable, and subseptation length as the outcome variable. Identifying a new subseptation length that warrants surgical intervention. RESULTS: Seventy-six women with subseptations and 77 with healthy uteri were included in the study. In the subseptate group, 50 had a subseptum less than 10 mm, and 26 were greater than 10 mm. Uterine and uterine cavity widths were significantly greater than in healthy women. The postoperative cavity width (28 ± 0.9 mm) was correlated with the preoperative subseptum length (R = 0.42; P = .016) and width (R = 0.54; P = .001) and was similar to healthy uteri. The receiver operator characteristic curve identified 5.9 mm (sensitivity = 100%, specificity = 41.4%) as a new threshold length of subseptation, which shows a postoperative cavity adjustment comparable to a subseptation greater than 10 mm. CONCLUSIONS: The relevance of subseptations shorter than 10 mm is currently undetermined and underestimated. Our data indicate a new subseptation cutoff length with postoperative remodeling and statistical relevance similar to longer subseptations. We propose a revision of the recommendations for surgical correction to include the objectively obtained subseptation length greater than or equal to 5.9 mm.

A One-Pot/Single-Analysis Approach to Substrate Scope Investigations Using Comprehensive Two-Dimensional Gas Chromatography (GC×GC).

A representative substrate scope investigation for an enantioselective catalytic ketone-reduction has been performed as a single reaction on a mixture containing equimolar amounts of nine (9) prototypical compounds. The resulting analyte pool containing 18 potential products from nine different reactions could all be completely resolved in a single chromatographic injection using comprehensive two-dimensional gas chromatography (GC×GC) with time-of-flight mass spectrometry, allowing for simultaneous determination of percent conversion and enantiomeric excess for each substrate. The results obtained for an enantioselective iron-catalyzed asymmetric transfer hydrogenation using this one-pot/single-analysis approach were similar to those reported for the individualized reactions, demonstrating the utility of this strategy for streamlining substrate scope investigations. Moreover, for this particular catalyst, activity and selectivity were not greatly affected by the presence of other ketones or enantioenriched reduced products. This approach allows for faster and greener analyses that are central to new reaction development, as well as an opportunity to gain further insights into other established transformations.

Effect of body mass index on self-reported exercise-triggered asthma.

INTRODUCTION: Exercise-induced asthma (EIA) is common in individuals diagnosed with asthma, with 80% to 90% experiencing asthma symptoms during moderate exercise. Asthma has been linked to obesity such that obesity may be a risk factor for adult-onset asthma. Adults with asthma disclose comorbid obesity as one of the most common barriers to exercise. Physical inactivity has been linked to increases in body mass index (BMI). Few studies have explicitly examined the relationship between BMI and reporting exercise as an asthma trigger. It was hypothesized that individuals with asthma who have an increased BMI will also have increased reports of exercise as an asthma trigger. METHODS: In total, 673 adult outpatients with asthma at Hôpital du Sacré-Cœur de Montréal in Montréal, Quebec, Canada underwent a brief sociodemographic and medical history interview. Patients provided information on their height, weight (used to calculate BMI), and triggers that generally provoked an asthma exacerbation (though it should be noted that a formal EIA test was not performed). RESULTS: When individuals were classified as normal, overweight, or obese, logistic regression analysis revealed that those who were overweight had a 95% increase in the likelihood of reporting exercise-triggered asthma (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.94) compared with those of normal weight, and this likelihood was more than doubled if the individuals were obese (OR, 2.34; 95% CI, 1.44-3.82). Assessing BMI as a continuous variable revealed that every 1-point increase in BMI was associated with a 9% increase in patients reporting exercise as a trigger (OR, 1.09; 95% CI, 1.04-1.14). All analyses were conducted adjusting for age, sex, asthma severity, and asthma control. CONCLUSION: Results suggest that BMI influences the likelihood of reporting exercise as an asthma trigger, such that individuals with higher BMIs report exercise as an asthma trigger more often than those with a lower BMI. Given that the current study is cross-sectional, further prospective research is needed to define the causal pathway of this relationship.

Analysis of information needs of users of MEDLINEplus, 2002 - 2003.

We analyzed query logs from use of MEDLINEplus to answer the questions: Are consumers' health information needs stable over time? and To what extent do users' queries change over time? To determine log stability, we assessed an Overlap Rate (OR) defined as the number of unique queries common to two adjacent months divided by the total number of unique queries in those months. All exactly matching queries were considered as one unique query. We measured ORs for the top 10 and 100 unique queries of a month and compared these to ORs for the following month. Over ten months, users submitted 12,234,737 queries;only 2,179,571 (17.8%) were unique and these had a mean word count of 2.73 (S.D., 0.24); 121 of 137 (88.3%) unique queries each comprised of exactly matching search term(s) used at least 5000 times were of only one word. We could predict with 95% confidence that the monthly OR for the top 100 unique queries would lie between 67% - 87% when compared with the top 100 from the previous month. The mean month-to-month OR for top 10 queries was 62% (S.D., 20%) indicating significant variability;the lowest OR of 33% between the top 10 in Mar.compared to Apr. was likely due to "new" interest in information about SARS pneumonia in Apr. 2003.Consumers' health information needs are relatively stable and the 100 most common unique queries are about 77% the same from month to month. Website sponsors should provide a broad range of information about a relatively stable number of topics. Analyses of log similarity may identify media-induced, cyclical,or seasonal changes in areas of consumer interest.

A methodology for modular representation of guidelines.

Computer-based clinical practice guidelines often need to be modified when medical knowledge evolves or when guidelines are implemented in a local setting with specific constraints and preferences. To enable easy modifications to guidelines and maintain their integrity, we have developed a methodology for modular representation of guidelines. Using this approach, we create guidelines in a hierarchical and modular manner. We use the Axiomatic Design methodology to facilitate the development of independent modules. Design matrices capture the interactions among modules. The design matrices can be used during guideline modification to create a change process and to enable identification of other modules that are affected by a change to a module. We implemented this modular knowledge representation approach by incorporating it into the Guideline Interchange Format (GLIF) language. We applied this approach to encode parts of three outdated guidelines released during 2000-2001, and we revised these designs to model updated releases of the guideline. Qualitative and quantitative metrics were developed to assess the types of changes made to the encoded guidelines.

Applying axiomatic design methodology for guideline revision.

We are investigating the use of axiomatic design (AD) as a principled approach to the revision of guidelines. AD models guidelines in a modular and hierarchical manner and captures interactions be-tween modules. To test this approach we applied AD to encode segments of three guidelines and their revised versions. Guideline encodings for the original versions were modified to incorporate changes made in the revised documents. The results indicate that AD is a promising approach for guideline modeling.