Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents With Chronic Hepatitis C Virus: Part 1 of the DORA Study.

The pangenotypic regimen of glecaprevir and pibrentasvir (G/P) is approved to treat adults with chronic hepatitis C virus (HCV) infection and has yielded high cure rates in adults in clinical trials. Approved treatment options for pediatrics may include ribavirin. A pangenotypic regimen for pediatric patients remains an unmet need. DORA is an ongoing phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in pediatric patients with chronic HCV. This analysis includes Part 1 of the study, conducted in adolescent patients 12-17 years of age given the adult regimen of G/P (300 mg/120 mg) once daily for 8-16 weeks according to the indication durations used in adults. Patients were either treatment naïve or experienced with interferon-based regimens. The primary PK endpoint was steady-state exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12). The secondary efficacy endpoints were on-treatment virologic failure, relapse, and reinfection. Safety and tolerability were monitored. Part 1 enrolled 48 adolescent patients infected with genotypes 1, 2, 3, or 4, of whom 47 were administered G/P. All 47 patients (100%) achieved SVR12. No on-treatment virologic failures or relapses occurred. PK exposures of glecaprevir and pibrentasvir were comparable to exposures in adults. No adverse events (AEs) led to treatment discontinuation, and no serious AEs occurred. Conclusion: Adolescent patients with chronic HCV infection treated with G/P achieved a comparable exposure to adults, 100% SVR12 rate, and safety profile consistent with that in adults. This pangenotypic regimen demonstrated 100% efficacy within the adolescent population in as little as 8 weeks of treatment.

Multistate US Outbreak of Rapidly Growing Mycobacterial Infections Associated with Medical Tourism to the Dominican Republic, 2013-2014(1).

During 2013, the Maryland Department of Health and Mental Hygiene in Baltimore, MD, USA, received report of 2 Maryland residents whose surgical sites were infected with rapidly growing mycobacteria after cosmetic procedures at a clinic (clinic A) in the Dominican Republic. A multistate investigation was initiated; a probable case was defined as a surgical site infection unresponsive to therapy in a patient who had undergone cosmetic surgery in the Dominican Republic. We identified 21 case-patients in 6 states who had surgery in 1 of 5 Dominican Republic clinics; 13 (62%) had surgery at clinic A. Isolates from 12 (92%) of those patients were culture-positive for Mycobacterium abscessus complex. Of 9 clinic A case-patients with available data, all required therapeutic surgical intervention, 8 (92%) were hospitalized, and 7 (78%) required ≥3 months of antibacterial drug therapy. Healthcare providers should consider infection with rapidly growing mycobacteria in patients who have surgical site infections unresponsive to standard treatment.

Negative pressure wound therapy technologies for chronic wound care in the home setting: A systematic review.

The use of negative pressure wound therapy (NPWT) is increasing in both the inpatient and outpatient settings. We conducted a systematic review on the efficacy and safety of NPWT for the treatment of chronic wounds in the home setting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature, up to June 2014. Two independent reviewers screened search results. Seven studies met our criteria for inclusion. Six of the studies compared NPWT devices to other wound care methods and one study compared two different NPWT technologies. Data were limited by variability in the types of comparator groups, methodological limitations, and poor reporting of outcomes. We were unable to draw conclusions about the efficacy or safety of NPWT for the treatment of chronic wounds in the home setting due to the insufficient evidence. Consensus is needed on the methods of conducting and reporting wound care research so that future studies are able inform decisions about the use of NPWT in the home environment for chronic wounds.

Use of complementary and alternative medicines by ambulatory patients.

BACKGROUND: Complementary and alternative medicines (CAM) include a number of different modalities to improve health. The popularity of such healing methods has increased, although reports of problems and adverse effects have also increased. Difficulties have also been identified in communication between patients and their providers. Previous reports concerning CAM may have undersampled lower socioeconomic groups as a result of the telephone survey techniques used. METHODS: All patients with valid appointments for internal medicine resident teaching clinics at 2 publicly supported centers were considered for eligibility. Patients were surveyed about current medications and a variety of CAM modalities. Medical records were reviewed for demographic information and to confirm diagnoses, allergies, medications, and any documented adverse effects. RESULTS: Use of CAM was common by 85.4% of patients, including those using some form of diet, exercise, and prayer. A smaller number (32.3%) were currently using alternate health care providers and products. About 5% of the population used 6 products or more. Use by this primarily poor urban population appeared similar to that in previous reports, with some exceptions. Expensive modalities were less frequently used, whereas use of prayer appears more prevalent. CONCLUSIONS: Complementary and alternate medical modalities are as commonly used by poor urban populations as by the general population. Quantification of use depends on the types of CAM used and the time frame asked. Although much of the use does not appear to be maladaptive, a small percentage of individuals have enthusiastically adapted CAM in ways that would not be endorsed by most allopathic physicians.

Antimicrobial stewardship in long-term care facilities.

Although antimicrobial stewardship has been shown to improve microbiologic susceptibility patterns, decrease drug toxicities, and lower overall drug costs in the inpatient setting, there are few studies assessing programs in the long-term care (LTC) setting. Implementing antimicrobial stewardship programs in LTC settings can be challenging as the LTC setting houses a unique population of frail and older adults with several preexisting conditions and multiple risk factors for colonization with multidrug-resistant organisms. Antimicrobial stewardship has an important role in decreasing inappropriate antibiotic use, encouraging targeted treatment of specific disease states, and limiting the untoward effects and costs of antimicrobials in this vulnerable population.

Clostridium difficile in the Pediatric Population of Monroe County, New York.

BACKGROUND: Clostridium difficile infection (CDI) incidence in hospitalized children has increased over the past decade and disease has been reported in the community. Therefore, population surveillance that includes nonhospitalized cases is important to accurately estimate the burden of CDI in children. We describe the epidemiology of CDI in the pediatric population of Monroe County, New York. METHODS: Active, laboratory, and population-based surveillance for CDI has been ongoing in Monroe County through the Emerging Infections Program of the Centers for Disease Control and Prevention since 2010. Infants less than 12 months of age are excluded. RESULTS: In 2010, the incidence of CDI in the pediatric population was 33.8 per 100 000 population, which increased to 45.8 in 2011and remained stable in 2012. Seventy-one percent of the CDI cases were community-associated, 60% had an underlying medical condition, and 71% received antibiotics before their illness. The North American pulsed-field gel electrophoresis type 1 (NAP1) epidemic strain was identified in 27% of cultured stool specimens. CONCLUSIONS: Clostridium difficile infection has emerged as a disease affecting children in both the community and hospital settings, with a higher proportion of community illness in our population. The majority of children with CDI had chronic underlying conditions and prior antibiotic exposure. To prevent CDI in this population, the judicious use of antibiotics, especially in the outpatient setting, may be the best strategy. Further population-based studies are warranted to determine preventable risk factors for CDI in the pediatric population.