Safety, efficacy and pharmacokinetics of peginterferon alpha2a (40 kd) in children with chronic hepatitis C

Chronic hepatitis C virus (HCV) infection in children is a problem affecting thousands of children worldwide. Although standard interferon (INF) has better efficacy in pediatric patients than in adults, results in children with genotype 1 are poor; response rates to combination treatment with standard INF and ribavirin are better but the treatment requires thrice-weekly injections. The improved antiviral efficacy of weekly pegylated interferons relative to standard interferons in adults with chronic HCV infection suggests that pegylated interferons may also improve antiviral efficacy in children. We therefore investigated the pharmacokinetics, efficacy and safety of peginterferon alpha2a (pegINF-alpha2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's body surface area (BSA) according to the formula BSA (m2)/(1.73 m2) x 180 microg, and patients were administered once-weekly subcutaneous injections for 48 weeks. Viral load and pharmacokinetic parameters were determined from blood drawn throughout the study and during follow-up. At week 24, the mean trough concentration was about 20% below values obtained from adults treated with pegINF-alpha2a, and the area under the curve from 0 to 168 hours was about 20% above adult values, suggesting that drug doses calculated from BSA achieved therapeutically adequate concentrations. Six of 14 patients (43%), all infected with genotype 1, achieved a sustained virological response. Adverse events were those commonly associated with INF-based treatment, and none was deemed serious. In conclusion, our findings provide a basis for larger studies evaluating the efficacy and safety of pegINF-alpha2a as monotherapy as well as in combination with ribavirin in pediatric patients with chronic hepatitis C.     

Improved preventive care for asthma: a randomized trial of clinician prompting in pediatric offices

OBJECTIVE: To determine whether clinician prompting regarding a child's symptom severity and guideline recommendations at the time of an office visit improves the delivery of preventive asthma care. DESIGN: Randomized controlled trial. SETTING: Two inner-city pediatric practices in Rochester, NY. PARTICIPANTS: Two hundred twenty-six children with persistent asthma (aged 2-12 years) presenting to the clinics for well-child care, asthma care, or non-asthma-related illness care.Intervention We assigned children randomly to a clinician-prompting group (single-page prompt including the child's symptoms and guideline recommendations given to the clinician at the time of the visit) or a standard-care group (no prompt given). Interviewers called parents after the visit to inquire about preventive measures taken, and medical charts were reviewed. MAIN OUTCOME MEASURES: Any preventive action related to asthma taken at the visit. RESULTS: Children in the clinician-prompting group were more likely to have had any preventive measures taken at the visit compared with children in the standard-care group (87% vs 69%). Specifically, visits for children in the clinician-prompting group were more likely to include delivery of an action plan (50% vs 24%), discussions regarding asthma (87% vs 76%), and recommendations for an asthma follow-up visit (54% vs 37%). In a regression model, children in the clinician-prompting group had 3-fold greater odds of receiving any preventive action compared with the standard-care group. CONCLUSION: Clinician prompting regarding asthma severity and care guidelines at the time of an office visit significantly improved the delivery of preventive asthma care.     

Role of prophylactic hysterectomy in patients at high risk for hereditary cancers

BACKGROUND: Current surgical recommendations for ovarian cancer prophylaxis in women at high risk of developing ovarian cancer include bilateral salpingo-oophorectomy (risk-reducing salpingo-oophorectomy (RRSO)). The role of hysterectomy is unclear. We sought to determine outcomes following prophylactic surgery in high-risk women. METHODS: We surveyed unaffected members of the Gilda Radner Familial Ovarian Cancer Registry who had undergone oophorectomy from 1981 to 2002. Data were collected and analyzed for statistical significance by the Fisher's Exact Test. RESULTS: Two hundred eighty women were surveyed, and 154 (55%) responded; 97% were Caucasian and 14% reported being Jewish. The median age of the respondents was 51 years (range 29-79); median age at oophorectomy was 41 years (range 15-68). Fifty-eight patients (38%) reported a laparoscopic procedure. One hundred five patients (68%) had a simultaneous hysterectomy, and 4 (3%) had a prior hysterectomy. Forty-four patients (29%) underwent BSO only. Of these 44 patients, 40 (91%) did not require a subsequent hysterectomy. Of the 4 who did, 2 were for leiomyomas, one for menorrhagia and the other was unknown. While not statistically significant, of the 3 patients who developed a subsequent gynecologic malignancy, all had undergone a hysterectomy. There was a statistically significant difference in whether or not the uterus was removed as part of the procedure by time period, whereby women treated prior to 1990 had a higher likelihood of having a hysterectomy (P = 0.03). CONCLUSION: The women in our study did not require hysterectomy for prevention of malignancy. We conclude that one should screen for benign gynecological indications for hysterectomy when planning a prophylactic BSO for prevention of ovarian cancer. Other potential risk factors for endometrial cancer, including the role of UPSC in HBOC, remain to be elucidated.     

The phenomenology of meditation for female survivors of intimate partner violence

An existential-phenomenological methodology was utilized to investigate the experience of meditation for female survivors of intimate partner violence. Six coresearchers were taught a form of concentrative meditation and were asked to meditate daily and to attend a weekly group meditation for 6 weeks. Semistructured interviews were utilized to gather the data. The essence of the experience that was revealed was the emergence of a centered awareness that is distinctly different from the usual mode of being in the world. Findings suggest the value of meditation as an intervention strategy with survivors and demonstrate the need for further research in this area.