Summary:Purpose: To examine the safety of lamotrigine (LTG) used in general practice to treat epilepsy.Methods: Information was collected on 11,316 patients who were included in a noninterventional observational cohort study conducted by means of Prescription-Event Monitoring (PEM). A follow-up study provided information on the first 3,994 patients who had taken LTG for 3 6 months. Incidence density (ID) measurements were used to rank the frequency of the reported events.Results: Rash was the most frequently reported nonepileptiform event (ID, 19.7/1,000 patient-months) in the first month of treatment and resulted in LTG being stopped in 2% of the 11,316 patients. Rash was reported more frequently among children aged 2-12 years (ID, 29.4/1,000 patient-months) than adults. Other events associated with the use of LTG included headache, drowsiness, nausea, vomiting, malaise, and lassitude.Rare serious events possibly associated with LTG included 12 cases reported as Stevens-Johnson syndrome, four cases of neutropenia, three cases of thrombocytopenia, and two cases of disseminated intravascular coagulation. There were also individual cases of leucopenia, a meningitic reaction, acute renal failure, hepatotoxicity, and a "lupus-like'' reaction possibly associated with the drug. No foetal abnormalities were specifically associated with the use of the drug in pregnancy. No death was attributed to LTG.Conclusions: Patients had severe epilepsy, inadequately controlled by other antiepileptic agents. The results of these two studies suggest that LTG is acceptably safe when used for the treatment of refractory epilepsy. Key Words: LamotrigineEpilepsy-Drug safety-Prescription-Event MonitoringRash.Lamotrigine (LTG) is a relatively new antiepileptic agent (AED) initially licensed as add-on therapy for seizures inadequately controlled by other drugs. LTG is therefore usually prescribed for patients with chronic, severe epilepsy, already being treated by other agents. The safety of LTG in these patients is of importance to both neurologists and general practitioners (GPs).A study was conducted by Prescription-Event Monitoring (PEM) to establish the safety of LTG. PEM identified events over an observation period of -6 months. As LTG is routinely intended for long-term use, a follow-up study was carried out to identify long-latency events in those patients who took the drug for >6 months.We report the results of the PEM study and the follow-up study.

BackgroundPreventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).MethodsThe primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.ResultsVarious reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.ConclusionSocio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.

Objective To determine the proportion and nature of congenital anomalies in babies born to Design Non-interventional observational cohort studies. MethodsThe women were identified in confidence by the Prescription Pricing Authority. The doctor was sent a questionnaire to determine clinical events, including pregnancy, occurring after the drug was dispensed. A supplementary questionnaire determined the outcome of each reported pregnancy.women exposed to newly marketed drugs during the first trimester.Setting General medical practice in England. Population Women exposed to newly marketed drugs in whom pregnancy was recorded.Main outcome measures Outcomes of pregnancies, the proportion and nature of congenital anomalies in the babies born.Results 251 1 pregnancies were reported. In 831 of these pregnancies a newly marketed drug had been taken during the first trimester and in 74 during the secondkhird trimester. The outcome was ascertained for 780 (94'1/0) of these 831 pregnancies: 547 (66'Yo) births; 10 (1%) ectopic pregnancies; 94 (1 1%) spontaneous miscarriages; 5 (< 1%) missed abortions; 120 (14%0) legal abortions; and 4 (C 1%) intrauterine deaths. 557 infants were born, of whom 14 (2.5%) had congenital anomalies. ConclusionsThe proportion of live infants with a congenital abnormality born to mothers exposed to newly marketed drugs in the first trimester was similar to the percentage of congenital anomalies estimated by the Ofice for National Statistics. These data add valuable information to the safety database of these drugs.

Aims Cough is one of the most frequent side effects associated with angiotensin converting enzyme inhibitors (ACEIs) but is not thought to be associated with losartan, an angiotensin II receptor antagonist (ARA). This study compares reports of cough with losartan and three ACEIs used in general practice. Methods Studies have been conducted for losartan, and three ACEIs enalapril, lisinopril and perindopril, using the technique of Prescription-Event Monitoring. Patients were identified using dispensed prescription data. Questionnaires were sent to patients' general practitioners 6 months after the date of first prescription. Cases of cough within the first 60 days of treatment with losartan resulting in withdrawal of the drug were followed up with additional questionnaires. Incidence rates for reports of cough were calculated. In order to reduce the impact of carry-over effects, rate ratios were calculated for first reports of cough between days 8 and 60 using losartan as the index drug. Results The cohort for each drug exceeded 9000 patients. Age and sex distributions and indications for prescribing the four drugs were similar. Cough was the most frequent reason for discontinuation of losartan and the most frequently reported event in the first month of treatment with this drug. When reports of cough between days 1-7 were excluded, rates of cough were significantly higher for the three ACEIs when compared with losartan (rate ratios 1.5, 4.8 and 5.7, all P<0.03). 101 patients had discontinued losartan due to cough. 91% of these had previously been prescribed an ACEI and 86% had previously experienced ACEI cough. Conclusions Carry-over accounted for the observed excess of reports of cough with losartan. Rates of cough between days 8 and 60 were significantly higher for the three ACEIs compared with losartan. Confounding factors associated with comparative observational cohort studies are discussed.

Risperidone is a relatively new antipsychotic agent licensed for the treatment of schizophrenia and other psychotic conditions in patients aged 15 years or older. This study examines the safety of risperidone used in general practice. Information was collected for 7684 patients included in a non-interventional observational cohort study conducted by means of Prescription-Event Monitoring. Incidence rates were calculated to rank the frequency of reported events. Drowsiness/sedation was the most frequent reason for stopping risperidone and the most frequently reported event. Extrapyramidal symptoms were reported rarely, but were more frequent in the elderly. 98 (1 . 3 per cent) patients were aged less than 15 years. Eight overdoses of risperidone alone were reported with no serious clinical sequelae. Risperidone appears to be well tolerated. #