Rationale: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of "no treatment" used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries.
Severe asthma in children is a complicated and heterogeneous disorder that is extremely challenging to treat. Although most children with asthma derive clinical benefit from daily administration of low-to-medium-dose inhaled corticosteroid (ICS) therapy, a small subset of children with "severe" or "refractory" asthma require high doses of ICS and even systemic corticosteroids to maintain symptom control. These children with severe asthma are at increased risk for adverse outcomes including medication-related side effects and recurrent and life-threatening exacerbations that significantly impair quality of life. This review highlights findings on severe asthma in school-age children (age 6-17 years) from the National Heart, Lung and Blood Institute's Severe Asthma Research Program (SARP) over a 10-year period, between 2001 and 2011. Although SARP has advanced knowledge of the unique clinical, biological, and molecular attributes of severe asthma in children, considerable gaps remain for which additional studies are needed.
Objective Anal cancer rates are increasing among HIV-infected persons. Although an efficacious human papillomavirus (HPV) vaccine is available, HPV vaccination rates remain low. Therefore, providers perform anal cancer screening, but there is no consensus on the optimal methods or timing of screening. This study was performed to determine the prevalence of and factors associated with anal squamous intraepithelial lesions in sexually active HIV-infected young men who have sex with men and transgender women. Materials and Methods We performed a single-center, retrospective study of sexually active HIV-infected young men who have sex with men and transgender women aged 13 to 24 years at an HIV clinic in Atlanta GA from 2009 to 2016. We used analysis of variance and χ2 tests of independence to evaluate bivariate associations and identify demographic, behavioral, and clinical risk factors. Results Of 314 subjects with a mean (SD) age of 20.4 (2.1) years at initial anal cytology testing, 5% had completed the HPV vaccine series at or before the time that cytology was obtained. Ninety-five percent of the anal cytology tests obtained were abnormal, and 72 (29%) of those subjects returned for diagnostic testing either by intraoperative biopsy or high-resolution anoscopy. Fifty-seven percent of those who underwent biopsy had histologic high-grade squamous intraepithelial lesions including 2 cases of carcinoma in situ. A history of greater than 20 lifetime sexual partners was associated with abnormal histology (probability < 0.001, p =.017). Conclusions Our study highlights the value of early, standardized screening to avoid missing anal dysplasia or cancer, particularly in unvaccinated persons with high numbers of sexual partners.
Objectives High-dose vitamin D3increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. Methods In a double blind, randomized controlled trial, critically ill ventilator-dependent adults (N = 30) received enteral vitamin D3(250,000 or 500,000 IU total over 5 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Results Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P < 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). Conclusions The present study found a dose-related increase in plasma free-25(OH)D levels, which was associated with increasing circulating mRNA expression of hCAP18 over time. There were no correlations between changes in total and free 25(OH)D against plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3administration on endogenous AMPs.
Purpose: This 2-year analysis assessed frequency of comorbidities and comorbidity screening in the Somatuline®(lanreotide, LAN) Depot for Acromegaly (SODA) registry. Methods: Patient data collected included pituitary hormone deficiencies, sleep studies, echocardiograms, gallbladder sonographies, colonoscopies, and glycated hemoglobin (HbA1c) levels. Insulin-like growth factor-1 (IGF-1) and growth hormone levels in patients with (DM) and without (non-DM) diabetes mellitus were analyzed. Results: There were 241 patients enrolled. Pituitary hormone deficiencies were reported more frequently at enrollment in male (56.9%) vs female patients (32.0%; p < 0.001). TSH deficiency was the most common endocrine deficiency (69.8%), followed by gonadotropin deficiency (62.3%). Screening tests reported at enrollment: sleep studies in 29.9% (79.2% had sleep apnea), echocardiogram in 46.1% (46.8% abnormal), gallbladder sonography in 18.7% (17.8% had gallstones), and colonoscopy in 48.1% (35.3% had polyps). Follow-up studies were reported less frequently at 1 and 2 years. HbA1c data were reported in 30.8% and 41.2% after 1 and 2 years. HbA1c levels were similar at 1 and 2 years of LAN therapy among DM and non-DM patients with available data. Fewer DM vs non-DM patients achieved IGF-1 below upper limit of normal at Month 24 (58.3% vs 80.6%; p = 0.033). Conclusions: Fewer than half of patients in SODA had screening results reported at enrollment for sleep apnea, cardiomyopathy, and colon polyps. Gallbladder imaging was reported in a minority of patients. Lower IGF-1 control rates were observed in DM vs non-DM patients at Month 24. These data suggest a need for better monitoring of comorbidities in US acromegaly patients.
2017 was a record year for disasters and disaster response in the U.S. Redefining and differentiating key response roles like "immediate responders" and "first responders" is critical. Traditional first responders are not and cannot remain the only cadre of expected lifesavers following a mass casualty event. The authors argue that the U.S. needs to expand its understanding of response roles to include that of the immediate responders, or those individuals who find themselves at the incident scene and are able to assist others. Through universal training and education of the citizenry, the U.S. has the opportunity increase overall disaster resiliency and community outcomes following large-scale disasters. Such education could easily be incorporated into high school curriculums or other required educational experiences in order to provide all persons with the knowledge, skills, and basic abilities needed to save lives immediately following a disaster.
Objective:
To describe system failures potentially contributing to perinatal HIV transmission in the state of Georgia, United States, between 2005 and 2012.
Design:
A retrospective chart review of antenatal and postnatal records of HIV-infected infants between 1 January 2005 and 31 December 2012.
Methods:
Study participants included all HIV-infected infants referred for specialized management to the Ponce Family and Youth Clinic within Grady Health Systems in Atlanta. Main outcomes included identification of maternal, perinatal, and neonatal risk factors associated with vertical transmission.
Results:
Twenty-seven cases were identified; 89% of mothers were African–American between 16 and 30 years of age. Seventy-four percent of women knew their HIV status prior to pregnancy, 44% had no prenatal care, and 52% did not receive combination antiretroviral therapy during pregnancy or intrapartum zidovudine. HIV-1 RNA near the time of delivery was available in only 10 of 27 mothers, and of those, only three had an undetectable HIV-1 RNA level. Caesarean section was performed in 70% of women. Of the 27 children, the mean gestational age was 37 (SD: 2.9) weeks, with 33% requiring neonatal ICU admission. Fifty-nine percent were men, and only 67% received postnatal zidovudine prophylaxis.
Conclusion:
Mother-to-child transmission of HIV continues to occur in Georgia at unacceptable levels. Increased education with adherence to existing national guidelines, as well as coordinated efforts between healthcare and public health providers to improve linkage and retention in medical care are urgently needed to prevent further vertical transmission events in Georgia.
Introduction: Hyperglycemia is associated with increased morbidity and mortality in critically ill patients and strict glycemic control has become standard care for adults. Recent studies have questioned the optimal targets for such management and reported increased rates of iatrogenic hypoglycemia in both critically ill children and adults. The ability to provide accurate, real-time continuous glucose monitoring would improve the efficacy and safety of this practice in critically ill patients. The aim of our study is to determine if a continuous, interstitial glucose monitor will correlate with blood glucose values in critically ill children.Methods: We evaluated 50 critically ill children age 6 weeks to 16 years old with a commercially available continuous glucose monitor (CGM; Medtronic Guardian®). CGM values and standard blood glucose (BG) values were compared. During the study, no changes in patient management were made based on CGM readings alone.Results: Forty-seven patients had analyzable CGM data. A total of 1,555 CGM and routine BG measurements were compared using Clarke error grid and Bland-Altman analysis. For all readings, 97.9% were within clinically acceptable agreement. The mean absolute relative difference between CGM and BG readings was 15.3%. For the 1,555 paired CGM and BG measurements, there is a statistically significant linear relationship between CGM values and BG (P <.0001). A high degree of clinical agreement existed in three subpopulation analyses based on age, illness severity, and support measures. This included some of our smallest patients (that is, <12 months old), those who required vasopressors, and those who were treated for critical illness hyperglycemia.Conclusions: In one of the largest studies to date, in a highly vulnerable ICU population, CGM values have a clinically acceptable correlation with the BG values now used diagnostically and therapeutically. Our data contest the theoretical concerns posed by some regarding CGM use in the ICU. The existing medical evidence may now support a role for CGM devices in the identification and management of hyperglycemia in diverse ICU settings.
by
Jennifer James;
David Munson;
Sara B. DeMauro;
John C. Langer;
April Dworetz;
Girija Natarajan;
Margarita Bidegain;
Christine A. Fortney;
Ruth Seabrook;
Betty R. Vohr;
Jon E. Tyson;
Edward F. Bell;
Brenda B. Poindexter;
Seetha Shankaran;
Rosemary D. Higgins;
Abhik Das;
Barbara Stoll;
Haresh Kirpalani
Objectives To describe the frequency of postnatal discussions about withdrawal or withholding of life-sustaining therapy (WWLST), ensuing WWLST, and outcomes of infants surviving such discussions. We hypothesized that such survivors have poor outcomes. Study design This retrospective review included registry data from 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Infants born at 22-28 weeks of gestation who survived >12 hours during 2011-2013 were included. Regression analysis identified maternal and infant factors associated with WWLST discussions and factors predicting ensuing WWLST. In-hospital and 18- to 26-month outcomes were evaluated. Results WWLST discussions occurred in 529 (15.4%) of 3434 infants. These were more frequent at 22-24 weeks (27.0%) compared with 27-28 weeks of gestation (5.6%). Factors associated with WWLST discussion were male sex, gestational age (GA) of ≤24 weeks, birth weight small for GA, congenital malformations or syndromes, early onset sepsis, severe brain injury, and necrotizing enterocolitis. Rates of WWLST discussion varied by center (6.4%-29.9%) as did WWLST (5.2%-20.7%). Ensuing WWLST occurred in 406 patients; of these, 5 survived to discharge. Of the 123 infants for whom intensive care was continued, 58 (47%) survived to discharge. Survival after WWLST discussion was associated with higher rates of neonatal morbidities and neurodevelopmental impairment compared with babies for whom WWLST discussions did not occur. Significant predictors of ensuing WWLST were maternal age >25 years, necrotizing enterocolitis, and days on a ventilator. Conclusions Wide center variations in WWLST discussions occur, especially at ≤24 weeks GA. Outcomes of infants surviving after WWLST discussions are poor. Trial registration ClinicalTrials.gov: NCT00063063.
Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.