Exposure to corticosteroids in pregnancy is associated with adverse perinatal outcomes among infants of mothers with inflammatory bowel disease: results from the PIANO registry.

OBJECTIVE: Active inflammatory bowel disease (IBD) during pregnancy may require the use of corticosteroids. The aim of this study was to investigate the impact of in utero corticosteroid exposure on adverse pregnancy outcomes, congenital malformations, infections and neurocognitive development among offspring of mothers with IBD. DESIGN: Using the prospective Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes registry, data were collected at each trimester, delivery; and in the 12 months post partum. Bivariate statistics and multivariate logistic regression models compared pregnancy outcomes by corticosteroid exposure. RESULTS: A total of 1490 mothers with IBD were enrolled, with 1431 live births recorded. Corticosteroid use was associated with increased risk of preterm birth, small for gestational age, low birth weight (LBW), intrauterine growth restriction and neonatal intensive care unit (NICU) admission. On adjusted multivariate models, corticosteroid use was associated with preterm birth (OR 1.79, 95% CI 1.18 to 2.73), LBW (OR 1.76, 95% CI 1.07 to 2.88) and NICU admission (OR 1.54, 95% CI 1.03 to 2.30). Late corticosteroid use (second and/or third trimester) was associated with serious infections at 9 and 12 months (4% vs 2% and 5% vs 2%, respectively, p=0.03 and p=0.001). There were five newborns with in utero corticosteroid exposure born with orofacial clefts versus one without corticosteroid exposure. Developmental milestones were similar across corticosteroid exposure groups. CONCLUSION: In this prospective pregnancy registry, offspring of women exposed to corticosteroids during pregnancy were more likely to have adverse pregnancy outcomes. This emphasises the importance of controlling disease activity before and during pregnancy with steroid-sparing therapy.

The effects of race and socioeconomic status on immunomodulator and anti-tumor necrosis factor use among ambulatory patients with inflammatory bowel disease in the United States.

OBJECTIVES: Health-care disparities exist for patients of minority race and low socioeconomic status (SES) in many chronic disease states, but little is known regarding health-care disparities for patients with inflammatory bowel disease (IBD). Using nationally representative data, we sought to determine whether use of immunomodulators and anti-tumor necrosis factor (TNF) agents differed by race/ethnicity and SES among ambulatory patients with IBD. METHODS: We used data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 1998 to 2010. We identified visits associated with IBD and the medications associated with those visits. Race/ethnicity and SES were characterized. The frequency of immunomodulator and anti-TNF use over time was assessed. We performed analyses accounting for the survey's complex multistage probability sampling design. Associations between race/ethnicity, SES and IBD medication use were identified. RESULTS: A total of 26,400,000 visits for patients with IBD occurred in the United States from 1998 to 2010. Seventy-six per cent of visits were for whites, 9% were for blacks, 7% were for Hispanics, and 2% were for Asians. Sixty-one per cent of visits were privately insured, whereas 7% had Medicaid coverage. From 1998 to 2010, the proportion of visits associated with immunomodulators increased from 6 to 13%, whereas the proportion associated with anti-TNF agents increased from <1 to 14%. In adjusted analyses, visits with Medicaid were three times more likely to be associated with immunomodulators than visits with private insurance, but there were no race/ethnicity-based differences in immunomodulator use. There were no race/ethnicity- or SES-based differences in anti-TNF therapy. CONCLUSIONS: Using nationally representative data over a 13-year time period, we found no evidence of disparities in medical therapy for IBD among visits with minority race/ethnicity or low SES.

Durability of infliximab dose intensification in Crohn's disease.

BACKGROUND: Dose intensification is a common approach to treat Crohn's disease (CD) patients who lose response to infliximab maintenance therapy. Few studies have reported upon its long-term efficacy or predictors of response. AIM: The goal of this study is to investigate durability and predictors of response to dose intensification-including method of dose intensification, combination immunomodulator therapy, and premedication with intravenous hydrocortisone. METHODS: We performed a retrospective study of dose-intensified CD patients at our institution. Dose intensification was defined as an increase in dose from 5 to 10 mg/kg, an increase in frequency of infusions from every 8 weeks to every 6 weeks or less, or both an increase in dose and frequency. RESULTS: Thirty CD patients (mean age, 39.9 years) met study criteria and underwent dose intensification. Ten (33.3%) patients remained on dose intensification at the end of our study or returned to their former infliximab dose or schedule (median follow-up, 41 months). Fourteen patients (46.7%) eventually lost response to dose intensification, but dose intensification extended infliximab therapy by a median duration of 9 months. Six patients (20%) didn't respond to dose intensification. Neither method of dose intensification, combination immunomodulator therapy, nor premedication with intravenous hydrocortisone predicted initial or durable response to dose intensification. However, analysis of predictors was limited by the small sample size of our study. CONCLUSIONS: The majority of CD patients respond to dose intensification, and a substantial portion will experience durable response such that infliximab therapy is successfully extended by one or more years.

Repeat 2-stage revision for recurrent infection of total hip arthroplasty.

Eleven patients who developed reinfection after 2-stage revision for infected total hip arthroplasty (THA) were treated with a repeat 2-stage rerevision. Of the 11 rerevisions, 4 were successful, with no recurrent infection at mean follow-up of 44 months. Reinfection occurred in 7 patients of whom 6 involved either a significantly compromised host or poor local wound status. Clinical symptoms of infection were controlled in 4 of the 7 reinfected cases with antibiotic therapy in 2, irrigation and debridement in 1, and a third 2-stage revision THA in 1. Repeat 2-stage treatment of infected THA is associated with a high failure rate. However, successful results can be achieved particularly if the host is not immunocompromised and healthy soft tissue coverage is present.

The family bereavement program: efficacy evaluation of a theory-based prevention program for parentally bereaved children and adolescents.

This article presents an experimental evaluation of the Family Bereavement Program (FBP), a 2-component group intervention for parentally bereaved children ages 8-16. The program involved separate groups for caregivers, adolescents, and children, which were designed to change potentially modifiable risk and protective factors for bereaved children. The evaluation involved random assignment of 156 families (244 children and adolescents) to the FBP or a self-study condition. Families participated in assessments at pretest, posttest, and 11-month follow-up. Results indicated that the FBP led to improved parenting, coping, and caregiver mental health and to reductions in stressful events at posttest. At follow-up, the FBP led to reduced internalizing and externalizing problems, but only for girls and those who had higher problem scores at baseline.

Pharmacokinetics of biologics and the role of therapeutic monitoring.

Biologic therapies, including the anti-tumor necrosis factor-α and cell adhesion molecule inhibitor drugs, have revolutionized the treatment of moderate-to-severe inflammatory bowel disease. Since the introduction of anti-tumor necrosis factor therapies, the strategy of empiric dose-escalation, either increasing the dose or frequency of administration, has been used to recapture clinical response in inflammatory bowel disease. Disparate clinical outcomes have been linked to serum drug and antidrug antibody levels. Therapeutic drug monitoring has emerged as a framework for understanding and responding to the variability in clinical response and remission.

Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response.

BACKGROUND: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling. METHODS: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks). RESULTS: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose-doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP). CONCLUSIONS: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy.

Resilience in parentally bereaved children and adolescents seeking preventive services.

This study examined environmental stress, family, and child variables that differentiate resilient children and adolescents from those with mental health problems following the death of a primary caregiver. The community-based sample included 179 bereaved children ages 8 to 16 years and their surviving caregivers who completed a test battery of measures before participating in a prevention program. Forty-four percent of bereaved children were classified as resilient and 56% as affected based on the absence of clinically significant mental health problems on at least 1 measure as reported by either the child, surviving caregiver, or teacher on standardized measures of mental health problems. Results of multivariate analyses indicated that bereaved resilient versus affected status was a function of both family and child variables. Higher levels of caregiver warmth and discipline and lower levels of caregiver mental health problems were family-level variables that significantly differentiated resilient children from affected children. Bereaved children's perceptions of less threat in response to negative events and greater personal efficacy in coping with stress were child-level variables that differentiated resilient from affected status. Family and child variables were entered into a discriminant function analysis that correctly classified 72% of the sample. The findings are consistent with a model of resilience in which multilevel variables account for children's positive adaptation following exposure to adversity.

Laboratory implementation of human papillomavirus testing.

Human papillomavirus testing is becoming an integral component of cervical cancer screening. Market forces will require most laboratories that perform Papanicolaou tests to develop a system for handling human papillomavirus testing also. Data and information are presented that may facilitate laboratories when addressing the following issues in the process of developing a human papillomavirus testing service: Which methodology is the best fit for the laboratory? Is it better to develop an in-house testing service or to send it out? How do I get started? What are the financial and economic issues, and how should they be managed?