Evaluation of Short Versus Long Courses of Antibiotics in Critically Ill Patients With Gram-Negative Bloodstream Infections.

BACKGROUND: Short courses of antibiotics (7-10 days) are effective for uncomplicated gram-negative bloodstream infections (GN-BSI). However, prior studies have been limited to small cohorts of critically ill patients. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of short courses of therapy compared with longer courses in patients admitted to the intensive care unit (ICU) with GN-BSI. METHODS: Propensity-matched, retrospective cohort study of critically ill patients with GN-BSI. The primary outcome was a composite of 30-day mortality or 60-day relapse. Secondary endpoints were components of the composite, 30-day relapse, cure with or without adverse drug events (ADE), and ADEs. Regression analysis was performed to identify factors predictive of the composite outcome. RESULTS: 225 patients were included in the propensity analysis, 145 in the long cohort and 80 in the short cohort. The primary outcome occurred in 3.8% of patients in the short group and 9.0% of patients in the long group (P = 0.24). There was no difference in 30-day mortality (3.8% vs 5.5%, P = 0.79), 60-day relapse (0% vs 3.4%, P = 0.23), or 30-day readmission (20% vs 22.8%, P = 0.76). ADEs were more common in the long group (47.2% vs 34.1%, OR 1.7, 95% CI 1.04-2.9), primarily attributable to diarrhea. CONCLUSION AND RELEVANCE: In critically ill patients with GN-BSI, there were no efficacy outcome differences in patients treated with a short course of antibiotics compared with longer. However, patients in the short group were less likely to experience ADE. These findings suggest that short courses of antibiotics are effective for GN-BSI in critically ill patients.

(Potential) Mishaps of High-Dose-Rate Vaginal Cuff Brachytherapy.

Considering how commonly vaginal cuff brachytherapy is used, there is relatively little literature regarding the potential, albeit low, risk for complications. We present 3 potentially serious mishaps involving cylinder misplacement, dehiscence, and excessive normal tissue irradiation due to unique anatomy. Three patients with potentially serious treatment errors were encountered in the authors' usual clinical practice. Each patient's records were reviewed for this report. For patient 1, computed tomography (CT) simulation revealed grossly inadequate cylinder insertion, which was most obvious on the sagittal view. For patient 2, CT simulation revealed that the cylinder extended beyond the perforated vaginal cuff and was surrounded by bowel. For patient 3, CT images were used only to verify cylinder depth. A standard library plan based on cylinder diameter and active length was used. In retrospect, the images revealed an unusually thin rectovaginal septum, with the lateral and posterior vaginal wall thickness estimated to be <2 mm. This patient's fractional normal tissue doses were calculated for this report, revealing a rectal maximum dose (per fraction) of 10.8 Gy, maximum dose that 2 cc of the organ receives of 7.4 Gy, and volume of the organ that receives the prescription dose or higher of 2.8 cc. All doses were far in excess of those anticipated for a minimal 0.5-cm vaginal wall depth. Vaginal cuff high-dose-rate brachytherapy is a high-volume, routine procedure. Even in experienced hands, however, it carries a risk of improper cylinder placement, cuff dehiscence, and excessive normal tissue dose, all of which could seriously affect outcomes. These potential mishaps would be better appreciated and avoided with more extensive use of CT-based quality assurance measures.

Coverage, inequity and predictors of hepatitis B birth vaccination in Myanmar from 2011-2016: results from a national survey.

BACKGROUND: Hepatitis B virus birth dose (HepB-BD) vaccination is recommended to reduce mother to infant transmission. We evaluated the HepB-BD status of women who gave birth between 2011 and 2016 (N = 3,583) using the 2015-2016 Myanmar Demographic and Health Survey. METHODS: Frequency distributions of HepB-BD vaccination across maternal and health system factors, concentration indices, and logistic regression models were used to estimate coverage, inequity, and factors associated with vaccination. RESULTS: The majority of participants were younger than 30 years of age, lived in rural areas, and were multiparous. Almost all received antenatal care (ANC), but only 43% received recommended ANC services, and 60% gave birth at home. The overall HepB-BD coverage rate was 26%. Vaccination coverage was higher in urban areas and was inequitably concentrated among children of more educated and wealthier women. HepB-BD coverage was also positively associated with receipt of ANC at non-governmental facilities, and delivery at a facility, skilled provider at birth and Cesarean delivery. After adjusting for sociodemographic and health system factors, receipt of the HepB-BD was positively associated with weekly media exposure, receipt of recommended ANC, and Cesarean delivery, and inversely associated with home delivery. CONCLUSIONS: Both socioeconomic and health systems factors influenced suboptimal and inequitable vaccination coverage. Improved access to quality ANC and delivery services may increase HepB-BD coverage although targeted approaches to reach home births are likely required to achieve national goals.

Clients' perceptions of barriers and facilitators to implementing hepatitis C virus care in homeless shelters.

BACKGROUND: Hepatitis C virus (HCV) is highly prevalent among homeless persons, yet barriers continue to impede HCV testing and treatment in this population. We studied the experiences of homeless individuals related to accessing HCV care to inform the design of a shelter-based HCV prevention and treatment program. METHODS: Homeless shelter clients (10 women and 10 men) of a large shelter in San Francisco participated in gender segregated focus groups. Focus groups followed a semi-structured interview format, which assessed individual, program/system, and societal-level barriers and facilitators to universal HCV testing and linkage to HCV care. Focus group interviews were transcribed, coded, and analyzed using thematic analysis. RESULTS: We identified key barriers to HCV testing and treatment at the individual level (limited knowledge and misconceptions about HCV infection, mistrust of health care providers, co-morbid conditions of substance use, psychiatric and chronic medical conditions), system level (limited advocacy for HCV services by shelter staff), and social level (stigma of homelessness). Individual, system, and social facilitators to HCV care described by participants included internal motivation, financial incentives, prior experiences with rapid HCV testing, and availability of affordable direct acting antiviral (DAA) treatment, respectively. CONCLUSIONS: Interrelated individual- and social-level factors were the predominant barriers affecting homeless persons' decisions to engage in HCV prevention and treatment. Integrated models of care for homeless persons at risk for or living with HCV address many of these factors, and should include interventions to improve patient knowledge of HCV and the availability of effective treatments.

Recommendations for Implementing Hepatitis C Virus Care in Homeless Shelters: The Stakeholder Perspective.

Compared with the general population, homeless individuals are at higher risk of hepatitis C infection (HCV) and may face unique barriers in receipt of HCV care. This study sought the perspectives of key stakeholders toward establishing a universal HCV screening, testing, and treatment protocol for individuals accessing homeless shelters. Four focus groups were conducted with homeless shelter staff, practice providers, and social service outreach workers (n = 27) in San Francisco, California, and Minneapolis, Minnesota. Focus groups evaluated key societal, system, and individual-level facilitators and barriers to HCV testing and management. Interviews were transcribed and analyzed thematically. The societal-level barriers identified were lack of insurance, high-out-of-pocket expenses, restriction of access to HCV treatment due to active drug and/or alcohol use, and excessive paperwork required for HCV treatment authorization from payers. System-level barriers included workforce constraints and limited health care infrastructure, HCV stigma, low knowledge of HCV treatment, and existing shelter policies. At the individual level, client barriers included competing priorities, behavioral health concerns, and health attitudes. Facilitators at the system level for HCV care service integration in the shelter setting included high acceptability and buy in, and linkage with social service providers. Conclusion: Despite societal, system, and individual-level barriers identified with respect to the scale-up of HCV services in homeless shelters, there was broad support from key stakeholders for increasing capacity for the provision of HCV services in shelter settings. Recommendations for the scale-up of HCV services in homeless shelter settings are discussed.

DLX4 is associated with orofacial clefting and abnormal jaw development.

Cleft lip and/or palate (CL/P) are common structural birth defects in humans. We used exome sequencing to study a patient with bilateral CL/P and identified a single nucleotide deletion in the patient and her similarly affected son­c.546_546delG, predicting p.Gln183Argfs*57 in the Distal-less 4 (DLX4) gene. The sequence variant was absent from databases, predicted to be deleterious and was verified by Sanger sequencing. In mammals, there are three Dlx homeobox clusters with closely located gene pairs (Dlx1/Dlx2, Dlx3/Dlx4, Dlx5/Dlx6). In situ hybridization showed that Dlx4 was expressed in the mesenchyme of the murine palatal shelves at E12.5, prior to palate closure. Wild-type human DLX4, but not mutant DLX4_c.546delG, could activate two murine Dlx conserved regulatory elements, implying that the mutation caused haploinsufficiency. We showed that reduced DLX4 expression after short interfering RNA treatment in a human cell line resulted in significant up-regulation of DLX3, DLX5 and DLX6, with reduced expression of DLX2 and significant up-regulation of BMP4, although the increased BMP4 expression was demonstrated only in HeLa cells. We used antisense morpholino oligonucleotides to target the orthologous Danio rerio gene, dlx4b, and found reduced cranial size and abnormal cartilaginous elements. We sequenced DLX4 in 155 patients with non-syndromic CL/P and CP, but observed no sequence variants. From the published literature, Dlx1/Dlx2 double homozygous null mice and Dlx5 homozygous null mice both have clefts of the secondary palate. This first finding of a DLX4 mutation in a family with CL/P establishes DLX4 as a potential cause of human clefts.