Inflammation plays a part in the etiology of dementia. Whether this is the primary pathogenesis, or a secondary reaction is unclear. We postulate that since systemic infection can provoke the enhanced synthesis of inflammatory mediators in the brain, such diseases may promote the onset of dementia. We carried out a nested case-control study using the General Practice Research Database. Cases were patients with incident dementia, and controls without such a diagnosis. Infectious episodes in the four years preceding diagnosis were counted using diagnostic codes, or prescription codes for anti-infective drugs. We considered age, sex, smoking, diabetes mellitus, and frequency of consultation as potential confounders. There were 9954 valid cases, and 9374 valid controls. Cases were on average older, more likely to be female, to smoke and to have diabetes, than the controls. There was an increased risk of diagnosis of dementia in those patients older than 84 with infections (OR for 2 or more infections compared with 0 or 1 = 1.4, 95% CI 1.2 to 1.7). Smoking and diabetes mellitus were also shown to markedly increase the risk of diagnosis of dementia. We have shown a positive association between episodes of infection and increased likelihood of diagnosis of dementia in the very elderly. Smoking and diabetes mellitus are associated with onset of dementia in the elderly. The evidence from this study may represent cause and effect, since there is a credible biologic explanation.

Objectives To investigate the frequency with which sedation was reported in post-marketing surveillance studies of four second generation antihistamines: loratadine, cetirizine, fexofenadine, and acrivastine. Design Prescription-event monitoring studies. Setting Prescriptions were obtained for each cohort in the immediate post-marketing period. Subjects Event data were obtained for a total of 43 363 patients. Main outcome measure Reporting of sedation or drowsiness. Results The odds ratios (adjusted for age and sex) for the incidence of sedation were 0.63 (95% confidence interval 0.36 to 1.11; P = 0

Aims To estimate the rates of common adverse events in patients treated with the proton pump inhibitors omeprazole, lansoprazole and pantoprazole in general practice in England. Methods In prescription‐event monitoring cohort studies, data on dispensed prescriptions prescribed by general practitioners in England soon after each drug was launched were linked to subsequent clinical events recorded by the prescriber. 16 205 patients prescribed omeprazole between June 1989 and June 1990, 17 329 patients prescribed lansoprazole between May and November 1994, and 11 541 patients prescribed pantoprazole between December 1996 and June 1997 were studied. Results The commonest adverse events in the omeprazole, lansoprazole and pantoprazole cohorts were diarrhoea (incidence: 0.18, 0.39 and 0.23 per 1000 days of exposure, respectively); nausea/vomiting (incidence: 0.16, 0.22 and 0.18 per 1000 days of exposure, respectively); abdominal pain (incidence: 0.17, 0.21 and 0.17 per 1000 days of exposure, respectively); and headache (incidence rates: 0.10, 0.17 and 0.15 per 1000 days of exposure, respectively). The remaining adverse events occurred at rates of less than 0.11 per 1000 days of exposure. There were little absolute differences in the rates of most events between the three proton pump inhibitors. However, diarrhoea was more commonly associated with lansoprazole compared with omeprazole (rate difference: 0.21 per 1000 days of exposure; 95% CI 0.17, 0.25; rate ratio: 2.11; 1.78, 2.51), and there was a clear age‐response relationship. Conclusions Adverse events occurred relatively infrequently in all three cohorts. There were only small absolute differences in event rates between the three drugs, although these data suggest the hypothesis that lansoprazole is associated with more frequent occurrence of diarrhoea, particularly in the elderly.

Background-The long term safety of agonists, particularly in patients with heart disease, has not been fully established. Rates and relative risks of non-fatal cardiac failure and ischaemic heart disease were calculated, comparing bambuterol and salmeterol with the reference drug nedocromil. Results-The age and sex adjusted relative risk of non-fatal cardiac failure associated with bambuterol was 3.41 (95% confidence limits (CL) 1.99 to 5.86) when compared with nedocromil. When salmeterol was compared with nedocromil the adjusted relative risk of non-fatal cardiac failure was 1.10 (95% CL 0.63 to 1.91). The adjusted relative risk of non-fatal ischaemic heart disease was 1.23 (95% CL 0.73 to 2.08) and 1.07 (95% CL 0.69 to 1.66) for bambuterol and salmeterol, compared with nedocromil, respectively. However, in the first month of exposure the adjusted relative risk of non-fatal ischaemic heart disease was 3.95 (95% CL 1.38 to 11.31) when bambuterol was compared with nedocromil. Conclusions-Caution should be exercised when prescribing long acting oral agonists to patients at risk of cardiac failure. More definitive evidence would come from prospective randomised trials. (Thorax 1998;53:558-562) Methods-This

The influence of contrasting lentic and lotic hydrological environments on the morphology of members of the Galaxias vulgaris species complex was examined. Morphological variation between habitat types was investigated by comparison of populations of Galaxias brevipinnis (inferred ancestor), Galaxias gollumoides (roundhead morphotype) and Galaxias vulgaris (flathead morphotype). Interspecific convergence and intraspecific divergence of morphological characters were demonstrated, representing general shifts in morphology towards a common functional form in particular hydrological environments. In all species, more lentic Galaxias had longer bodies; shorter, more stout caudal peduncles; longer, narrower pectoral fins; and longer, wider heads with larger mouths. In comparison, lotic Galaxias had relatively shorter bodies; more slender caudal peduncles; broader pectoral fins; and shorter flatter heads, with smaller mouths. This study suggests that the hydrological environment of a habitat is an important factor moulding and maintaining an individual fish’s morphology to a particular habitat type, most likely representing a phenotypic plastic response.

SUMMARYObjective Ð To compare the safety and side-eect pro®les of the four selective serotonin reuptake inhibitor antidepressants (SSRIs),¯uvoxamine,¯uoxetine, sertraline and paroxetine.Methods Ð The results from four observational cohort studies of the four SSRIs were compared. Each of these studies was conducted by Prescription-Event Monitoring (PEM). The exposure data were derived from general practitioner (GP) prescriptions con®dentially supplied by the Prescription Pricing Authority (PPA) in England. Outcome data were obtained from questionnaires (green forms) on which the prescribing doctor recorded event data. The main ®ndings comprised demographic information, including patients' date of birth and sex; the indication for prescribing the monitored drug; the eectiveness of the drug as perceived by the GP; the reasons for stopping treatment and all events recorded during and after treatment.Results Ð The ®nal cohort for each of the four SSRIs exceeded 10,000 patients. The sex, age distributions and indications for prescribing the four SSRIs were very similar. Only 36% of the GPs expressing an opinion reported¯uvoxamine as eective, compared with approximately 60% for uoxetine, sertraline and paroxetine. Fluvoxamine was associated with a higher incidence of adverse events than the other three SSRIs. Nausea/vomiting was both the most frequent clinical reason for stopping all four SSRIs and the most frequently reported clinical event. Adverse events reported in patients aged 70 years and over were comparable with the events reported for the total cohorts. Dierences were identi®ed between the four SSRIs for less frequently reported adverse events. Withdrawal symptoms were signi®cantly more frequent with paroxetine than the other three SSRIs.Conclusions Ð The data from the four studies were comparable in terms of age distribution, sex of patients and indication for prescribing the drugs. Fluvoxamine had a considerably higher incidence of side-eects associated with its use than the other three SSRIs. The side-eect pro®les of the four SSRIs were comparable for frequently reported events. Important dierences were identi®ed between the four SSRIs in respect of less frequently reported events. This study suggests that¯uvoxamine compares unfavourably with¯uoxetine, sertraline and paroxetine, both in terms of reported eectiveness and the incidence of adverse events. Biases possibly aecting the comparisons involved in this study are unlikely to account for the observed dierences between¯uvoxamine and the other three SSRIs. #

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Objective —To compare the safety and side‐effect profiles of the four selective serotonin reuptake inhibitor antidepressants (SSRIs), fluvoxamine, fluoxetine, sertraline and paroxetine. Methods —The results from four observational cohort studies of the four SSRIs were compared. Each of these studies was conducted by Prescription‐Event Monitoring (PEM). The exposure data were derived from general practitioner (GP) prescriptions confidentially supplied by the Prescription Pricing Authority (PPA) in England. Outcome data were obtained from questionnaires (green forms) on which the prescribing doctor recorded event data. The main findings comprised demographic information, including patients' date of birth and sex; the indication for prescribing the monitored drug; the effectiveness of the drug as perceived by the GP; the reasons for stopping treatment and all events recorded during and after treatment. Results —The final cohort for each of the four SSRIs exceeded 10,000 patients. The sex, age distributions and indications for prescribing the four SSRIs were very similar. Only 36% of the GPs expressing an opinion reported fluvoxamine as effective, compared with approximately 60% for fluoxetine, sertraline and paroxetine. Fluvoxamine was associated with a higher incidence of adverse events than the other three SSRIs. Nausea/vomiting was both the most frequent clinical reason for stopping all four SSRIs and the most frequently reported clinical event. Adverse events reported in patients aged 70 years and over were comparable with the events reported for the total cohorts. Differences were identified between the four SSRIs for less frequently reported adverse events. Withdrawal symptoms were significantly more frequent with paroxetine than the other three SSRIs. Conclusions —The data from the four studies were comparable in terms of age distribution, sex of patients and indication for prescribing the drugs. Fluvoxamine had a considerably higher incidence of side‐effects associated with its use than the other three SSRIs. The side‐effect profiles of the four SSRIs were comparable for frequently reported events. Important differences were identified between the four SSRIs in respect of less frequently reported events. This study suggests that fluvoxamine compares unfavourably with fluoxetine, sertraline and paroxetine, both in terms of reported effectiveness and the incidence of adverse events. Biases possibly affecting the comparisons involved in this study are unlikely to account for the observed differences between fluvoxamine and the other three SSRIs. © 1997 John Wiley & Sons, Ltd.