Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy - A systematic review of the literature using lacosamide as an example.

Extrapolation of efficacy data from adults to children is accepted for focal epilepsy - the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome.

A Prospective Study Assessing Tumour Response, Survival, and Palliative Care Outcomes in Patients with HIV-Related Kaposi's Sarcoma at Queen Elizabeth Central Hospital, Blantyre, Malawi.

Background. Human-Immunodeficiency-Virus- (HIV-) related Kaposi's sarcoma (KS) has a high prevalence in Africa; however, there is minimal published data on treatment and outcomes in this population. Objective and Design. This was a prospective study of 50 patients, aiming to assess the impact of vincristine therapy on tumour response and survival and to assess palliative care outcomes in patients with HIV-related KS. Methods. 50 consecutive patients were recruited during 2008. Vincristine therapy and highly active antiretroviral therapy (HAART) were given. Tumour response, survival, and chemotherapy-related toxicities were documented. Palliative care outcomes were assessed using the African Palliative Care Association (APCA) Palliative Outcome Scale (POS). Results. The majority of patients were male, and the median age was 33 years. At baseline assessment, the median CD4 T-cell count was 263, and 50% patients had evidence of peripheral neuropathy. The overall response rate was 64% at 6 weeks, and median progression-free survival was 30 weeks. Treatment was generally well tolerated, with peripheral neuropathy the main dose-limiting toxicity. Conclusion. The combination of vincristine and HAART is feasible and effective in a low resource setting, although peripheral neuropathy is a dose-limiting factor. This patient group carries a high mortality and as such adequate access to palliative care is crucial.

Acceptability and experience of supportive companionship during childbirth in Malawi.

OBJECTIVE: To study the acceptability and experience of supportive companionship during childbirth by mothers, health professionals and supportive companions. DESIGN: Cross-sectional surveys before and after introducing supportive companionship. SETTING: Maternity facilities in Blantyre City, Malawi. POPULATION: Mothers who had normal deliveries before discharge from hospital, health professionals in health facilities and women from the community, who had given birth before and had interest in providing or had provided support to fellow women during childbirth. METHODS: Combined qualitative and quantitative methods. MAIN OUTCOME MEASURE: Perceptions on labour companionship among participants. RESULTS: The majority of supported women (99.5%), companions (96.6%) and health professionals (96%) found the intervention beneficial, mainly for psychological and physical support to the labouring woman and for providing assistance to healthcare providers. Some companions (39.3%) unwillingly accompanied the women they were supporting and 3.5% of companions mentioned that their presence in the labour ward was an opportunity for them to learn how to conduct deliveries. CONCLUSION: Supportive companionship for women during childbirth is highly acceptable among mothers and health professionals, and the community in Malawi, but should be governed by clear guidelines to avoid potential harm to labouring women. Women require information regarding the need for a supportive companion and their expected role before they present at a health facility in labour. Such notification will provide an opportunity for the pregnant woman to identify someone of their choice who is ready and capable of safely taking up the role of a companion.

Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States.

OBJECTIVE: To describe characteristics of vasomotor symptoms, specifically daily frequency and severity, among women 40-65 years old in the United States (US). DESIGN: A survey was completed by a nationally representative sample of 4402 US women aged 40-65 years old. A questionnaire focusing on menopausal symptoms was administered online in April 2005. RESULTS: The prevalence of vasomotor symptoms was 79% in peri- and 65% in postmenopausal women. Women with daily vasomotor symptoms had an average of 2.5 very mild/mild, 2.6 moderate, 2.5 severe, and 1.4 very severe daytime hot flushes in a typical day. Women with night sweats every night had an average of 2.4 moderate, 3.2 severe, and 2.7 very severe night sweats in a typical night. Overall, 9% of peri- and 7% of postmenopausal women reported 7+ moderate to very severe vasomotor symptoms in a typical day. Although some women reported that symptoms were worse in the evening and in the summer, many women reported they were consistent, both throughout the day and throughout the seasons of the year. CONCLUSIONS: The Menopause Epidemiology Study builds upon existing literature by providing data on daily frequency and severity of vasomotor symptoms. There are many women with frequent and severe vasomotor symptoms who may benefit from treatment.