The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.

BACKGROUND: Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine. INTERPRETATION: Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.

The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.

BACKGROUND: Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1.57 [95% CI 1.19-2.08]), but there was no significant difference between valproate and lamotrigine (1.25 [0.94-1.68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1.55 [1.07-2.24] and topiramate (1.89 [1.32-2.70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0.76 [0.62-0.94]), and for the subgroup with an idiopathic generalised epilepsy 0.68 (0.53-0.89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy. INTERPRETATION: Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.

The development of non-insulin-dependent diabetes after total body irradiation and bone marrow transplantation in adolescence: a case report and literature review.

A 6-yr-old-child received total body irradiation (TBI) and bone marrow transplantation (BMT) for relapsed acute lymphocytic leukemia. Nine years later, he developed diabetes mellitus (DM). He was started on basal bolus insulin therapy. Islet cell and anti-GAD antibodies were negative. Insulin and C-peptide levels were elevated consistent with insulin resistance (IR), even though his body mass index (BMI) was only 19.5. Hepatocyte nuclear factor (HNF-1alpha) mutation was not detected. Insulin was stopped and hemoglobin Alc (HbA1c) stabilized at 6.5% on gliclazide 40 mg/day. TBI has rarely been associated with IR and the development of diabetes. These patients can be managed with oral hypoglycemic agents and do not necessarily require insulin. Patients who received BMT and TBI may require long-term monitoring of glucose and lipid metabolism.

Children's home nursing: results of a national survey.

A questionnaire survey was undertaken to establish the characteristics of children's home nursing teams in the UK that deal with acute and chronic cases, to assess their impact on hospital referrals and determine whether they are cost effective. The sample consisted of acute and community trusts listed on the Royal College of Pediatrics and Child Health (RCPCH) database. Differences were found in trust affiliation, staffing, skill mix, caseload, procedures undertaken and hours of operation. Variations depend on whether teams had a predominantly acute caseload, dealt with a mixture of acute and chronic cases, or dealt with predominantly chronic cases. Thirty-two per cent of respondents stated that home care replaced inpatient care for the majority of the children. Budgets of home nursing services varied enormously with a very clear relationship between budget and staffing levels. This survey shows that in 2001, many trusts in the UK provide a children's hospital at home or home nursing service, but that the scale and scope of these services vary widely. Further research is needed on several aspects of home care including the relative costs and benefits of different forms of service in comparison to hospital-based care.