Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults--a report on 90 patients

Data on 90 patients (55 adults and 35 children) with chronic idiopathic thrombocytopenic purpura (ITP) and a platelet count of <50 x 10(9)/L treated with dapsone at a dose of 1-2 mg/kg/d are presented. A response was observed in 57 (63.3%) patients. The average time for response was 3.5 months (range 1-9) and the average duration of treatment with dapsone was 10.4 months (range 4-14). Overall response rates of 65.7% and 61.8% were observed in children and adults respectively. Side effects requiring discontinuation of therapy were observed in three (2%) patients. These results demonstrate that dapsone is an effective, inexpensive and well-tolerated treatment for chronic ITP, in both children and adults and could be considered for patients who fail steroid therapy.     

Surgery for hemophilia in developing countries

Surgical interventions in patients with hemophilia (PWH) in the developing world are difficult in the setting of limited availability of factor concentrates. Although the adequacy of international guidelines for factor concentrate prophylaxis for PWH undergoing surgery has been established, frequently it is not practical in the developing world. These recommendations were not established based on large clinical trials and fail to define the safe lower limit of factor concentrate prophylaxis for surgery. The need to define these lower limits is essential in the developing world so that the limited resources may be used optimally for the cohort of PWH. There are limited data from the developing world with regard to PWH undergoing surgical procedures. In this article, we outline experience from our institution, a tertiary referral center for hemophilia care in India. We trace the basis on which our current factor concentrate prophylaxis regimen (which is lower than that recommended internationally) was established. In our experience our low-dose protocols are effective, reduce factor consumption by one third, and are not associated with a significantly increased risk of delayed hemorrhage. We hope that this experience will form a framework on which guidelines can be established for developing countries.     

MODELING THE EFFECTS OF IMMUNIZATIONS TIMING ON CHILD HEALTH OUTCOMES IN INDIA

Timely vaccinations of children in developing countries are important for reducing morbidity and mortality, which are Millennium Development Goals. However, a majority of children do not possess vaccination cards compiling information on timing. We investigated the benefits of vaccination cards for the uptake of immunizations against diphtheria, pertussis and tetanus (DPT), polio, tuberculosis (BCG), and measles using data on over 200,000 Indian children from the District Level Health and Facility Survey 3. Methodological issues such as whether parents of children with higher morbidity levels may have them vaccinated were investigated. The results from the models for DPT, polio, measles, and BCG vaccinations showed significant beneficial effects of maternal education, household possessions, and access to health care facilities. Moreover, models for children's ages at the time of vaccination showed significant interactions between maternal education and access to and availability of health care facilities. Finally, models for child morbidity due to diarrhea, cough, and fever showed that timely vaccinations against DPT, access to piped water, and cooking with electricity or natural gas were associated with lower morbidity. Overall, issuing paper or electronic vaccination cards to children is likely to enhance timely uptake of various immunizations thereby reducing child morbidity. Copyright © 2013 John Wiley & Sons, Ltd.     

Novel mGluR5 Positive Allosteric Modulator Improves Functional Recovery,Attenuates Neurodegeneration,and Alters Microglial Polarization after Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) causes microglial activation and related neurotoxicity that contributes to chronic neurodegeneration and loss of neurological function. Selective activation of metabotropic glutamate receptor 5 (mGluR5) by the orthosteric agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), is neuroprotective in experimental models of TBI, and has potent anti-inflammatory effects in vitro. However, the therapeutic potential of CHPG is limited due to its relatively weak potency and brain permeability. Highly potent, selective and brain penetrant mGluR5 positive allosteric modulators (PAMs) have been developed and show promise as therapeutic agents. We evaluated the therapeutic potential of a novel mGluR5 PAM, VU0360172, after controlled cortical impact (CCI) in mice. Vehicle, VU0360172, or VU0360172 plus mGluR5 antagonist (MTEP), were administered systemically to CCI mice at 3 h post-injury; lesion volume, hippocampal neurodegeneration, microglial activation, and functional recovery were assessed through 28 days post-injury. Anti-inflammatory effects of VU0360172 were also examined in vitro using BV2 and primary microglia. VU0360172 treatment significantly reduced the lesion, attenuated hippocampal neurodegeneration, and improved motor function recovery after CCI. Effects were mediated by mGluR5 as co-administration of MTEP blocked the protective effects of VU0360172. VU0360172 significantly reduced CD68 and NOX2 expression in activated microglia in the cortex at 28 days post-injury, and also suppressed pro-inflammatory signaling pathways in BV2 and primary microglia. In addition, VU0360172 treatment shifted the balance between M1/M2 microglial activation states towards an M2 pro-repair phenotype. This study demonstrates that VU0360172 confers neuroprotection after experimental TBI, and suggests that mGluR5 PAMs may be promising therapeutic agents for head injury.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-014-0298-6) contains supplementary material, which is available to authorized users.     

National survey of perineal trauma and its subsequent management in the United Kingdom

Introduction and hypothesis

Perineal trauma affects approximately 350,000 women per annum in the United Kingdom (UK) and is associated with considerable morbidity. Symptoms are most severe following obstetric anal sphincter injuries (OASIS) compared with other grades of perineal trauma. The Royal College of Obstetricians and Gynaecologists (RCOG) guidelines indicate that the rate of OASIS is 1 % of vaginal deliveries. In 2011, the RCOG implemented the “Maternity Dashboard” so that units could benchmark their performance against national standards of which OASIS is a component. Our primary objective was to establish the national rate of OASIS and audit variations in incidence and management of obstetric perineal trauma.

Methods

We carried out a questionnaire-based survey auditing national practice. Every UK maternity unit was contacted regarding perineal outcomes after all deliveries between January 2009 and January 2010.

Results

215 of the 265 units in the UK responded (81 %). 692,259 of the 790,197 deliveries in the UK for the same period were sampled (88 %). 75 % delivered vaginally. The median national OASIS rate was 2.85 % (0–8 %). 20.2 % of women delivering vaginally had episiotomies; none were midline. 12.4 % of second-degree tears were not repaired in low-risk units compared with 5.9 % in high-risk units. 57.1 % of units used the perineal trauma classification of the RCOG.

Conclusions

This study provides comprehensive data regarding the incidence and management of perineal trauma across the UK. Clinicians and policy-makers, both local and at the RCOG, can devise up-to-date realistic guidelines on the anticipated rate of OASIS and help to assess the compliancy of units with guidelines on the appropriate management of perineal trauma.