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Biomedical subjects

G L Pearce

Publications and source records attributed to G L Pearce.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nefazodone in community use: the results of prescription-event monitoring.

PURPOSE: This study was a pharmacovigilance exercise which aimed to determine the post-marketing event profile of nefazodone, a newly marketed antidepressant, in community use. METHODS: Information was collected on patients included in a non-interventional observational cohort study conducted by means of Prescription-Event Monitoring in England. Incidence densities were calculated for all reported events. RESULTS: Information was obtained for 11 834 patients. Nausea and dizziness were the most frequent adverse events that led to stopping nefazodone and the most frequently reported events during the first month of treatment. Unsteadiness and falls were reported more frequently in the elderly. Hepatic events, involuntary movements, thrombocytopenia, hallucinations and withdrawal reactions were reported rarely but were possibly associated with nefazodone. Eight overdoses involving nefazodone alone were reported with no serious clinical sequelae. Two premature births, one low birth weight term baby and two babies with renal abnormalities were outcomes in 38 pregnancies exposed in the first trimester to nefazodone. One death in a woman aged 71 years followed an illness with serotonergic features. CONCLUSIONS: Event data are presented for patients dispensed nefazodone in the community. The findings are discussed.

Journal Article↗
PubMed1999

Cough and angiotensin II receptor antagonists: cause or confounding?

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.

Aged↗
PubMed1999

Newer antidepressants: a comparison of tolerability in general practice.

BACKGROUND: An increasing number of antidepressants have been released on the United Kingdom market in recent years, and these are being prescribed more frequently in general practice. Clinical trials suggest that such agents have similar efficacy and the choice of drug is probably based on tolerability, toxicity in overdose, and cost. AIM: To compare the tolerability and safety profile of six, newly marketed antidepressants used in general practice. METHOD: Studies have been conducted for six antidepressants: fluoxetine, sertraline, paroxetine, moclobemide, venlafaxine, and nefazodone, using the technique of prescription-event monitoring. Patients were identified using incident dispensed prescription data. Questionnaires were sent to patients' general practitioners six months after the date of first prescription. Questionnaires asked for date of birth, sex, indication for prescribing each drug, and all events entered in the patients' records after the date of first prescription. RESULTS: Each cohort exceeded 10,000 patients. Nausea/vomiting was the most frequently reported event for all drugs. The difference in incidence rates for drowsiness/sedation, male sexual dysfunction, and hypertension is shown. Mortality data are also reported. CONCLUSION: Frequently reported events were similar for all six drugs but there were clinically and statistically significant differences for less frequently reported events. The adjusted mortality rate was identical between the six drugs. This study provides valuable comparative data for six, widely used antidepressants in general practice.

Adult↗
PubMed1998

Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies.

AIMS: Little is known about the frequency with which suspected adverse drug reactions are seen by general practitioners after the prescription of newly marketed drugs. We investigated age and sex specific incidence rates of suspected adverse drug reactions recorded by general practitioners in England after the prescription of selected newly marketed drugs. METHODS: Information was collected from 48 national cohort studies of newly marketed drugs studied by prescription-event monitoring. Questionnaires were sent to prescribers asking for details of events and suspected adverse drug reactions recorded in the patients' notes occurring after the drugs were prescribed. RESULTS: During the 48 cohort studies, a total of 513608 patients were investigated, of which 221781 (43.2%) were males and 285862 (55.7%) were females. The overall incidence of suspected adverse drug reactions in males was 12.9 per 10000 patient-months of exposure (95% confidence limits 12.3 to 13.5), and in females was 20.6 per 10000 patient-months of exposure (95% confidence limits 19.9 to 21.3). The overall age-standardised relative risk of an adverse drug reaction in females compared with males was 1.6 (1.5-1.7). This sex difference was significant in all age groups above 19 years of age, and was relatively consistent across all age groups (chi2 test for heterogeneity = 9.2, P=0.3). The highest rate of recording in males was in the 50-59 year age group, and in females was in the 30-39 year age group. CONCLUSIONS: In general practice in England, suspected adverse drug reactions to newly marketed drugs are recorded more often in adults aged between 30 and 59 years of age and are 60% more common in women than in men. The sex difference occurs in all age groups over 19 years of age.

Adult↗
PubMed1998

The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England.

OBJECTIVE: To determine the proportion and nature of congenital anomalies in babies born to women exposed to newly marketed drugs during the first trimester. DESIGN: Non-interventional observational cohort studies. METHODS: The 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. 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: 2511 pregnancies were reported. In 831 of these pregnancies a newly marketed drug had been taken during the first trimester and in 74 during the second/third trimester. The outcome was ascertained for 780 (94%) of these 831 pregnancies: 547 (66%) births; 10 (1%) ectopic pregnancies; 94 (11%) spontaneous miscarriages; 5 (< 1%) missed abortions; 120 (14%) legal abortions; and 4 (< 1%) intrauterine deaths. 557 infants were born, of whom 14 (2.5%) had congenital anomalies. CONCLUSIONS: The 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 Office for National Statistics. These data add valuable information to the safety database of these drugs.

Abnormalities, Drug-Induced↗
PubMed1998

Port-access cardiac surgery protocols and early outcomes.

As a new cardiac surgical procedure, port-access holds promise to significantly impact the surgical approaches for treatment of CAD. Supporting collaborative practice protocols contributes to early extubation, rapid in-hospital recovery, and shortened LOS. Discharge protocols address postoperative concerns. Early results suggest that patient recovery is shorter than the time for conventional procedures; patients are able to return to an active lifestyle that is beneficial to families, patients, and employers.

Coronary Artery Bypass↗
PubMed1998

United Kingdom experience with alendronate and oesophageal reactions.

Alendronate is indicated for the treatment of osteoporosis in post-menopausal women. Although the drug has been associated with reports of severe oesophagitis, there have been no studies establishing the incidence of such reactions. Information was collected on 1523 patients included in a study conducted by means of prescription-event monitoring. Dyspepsia, nausea/vomiting, and abdominal pain were the most frequently reported events in the first month of treatment. After follow-up, 20 patients (1.3%) experienced oesophageal events that were considered to be possibly related to alendronate.

Aged↗
PubMed1997

A comparison of fluvoxamine, fluoxetine, sertraline and paroxetine examined by observational cohort studies.

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.

Journal Article↗
PubMed1997

A comparison of two cohort studies evaluating the safety of cisapride: Prescription-Event Monitoring and a large phase IV study.

OBJECTIVE: The results of Prescription-Event Monitoring (PEM) from over 13,000 patients receiving cisapride are compared with safety data from a large-scale clinical study involving nearly 10,000 patients. RESULTS: The clinical study population showed a significantly younger age profile than the PEM population and excluded patients with serious disease; however, both studies showed similar patterns of adverse events. The most common adverse events reported in association with cisapride in both studies were diarrhoea, headache, abdominal pain, constipation and nausea. Some of these may be attributed to the underlying condition rather than the action of the drug. Prompting patients about adverse events during a clinical trial assessment appeared to increase the reporting of some conditions: for example, diarrhoea was reported more frequently in the clinical trial than in the PEM study. CONCLUSION: Both studies showed cisapride to be generally safe and well tolerated.

Adolescent↗
PubMed1997

Safety of long-term lamotrigine in epilepsy.

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 > or = 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.

Adolescent↗
PubMed1996

ACE-inhibitor-induced cough, an adverse drug reaction unrecognised for several years: studies in prescription-event monitoring.

OBJECTIVE. This study examines cough recorded in Prescription-Event Monitoring (PEM) of four ACE-inhibitors. Particular attention was paid to the study of enalapril because the drug was monitored before the causal relationship between cough and ACE-inhibitors had been widely accepted. RESULTS. Several factors which had obscured the causal relationship in the individual cases were found to be also an obstacle in PEM. For example, cough was a common and non-serious event and was under-reported in the PEM study of enalapril and the rate was not strikingly different from that recorded for other drugs. Cough induced by ACE-inhibitors has several characteristics which reduce the chance of a recognisable "signal'. The original questionnaires returned from doctors in the PEM study of enalapril have been reexamined. The observation that the rate of cough diminished after enalapril had been stopped rather than increased after starting, provided the best evidence of causality, because this was not affected by many biases such as the publicity that had occurred prior to doctors participating in PEM completed later reports.

Adult↗
PubMed1996

A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies.

1. The safety in everyday clinical usage of three 4-quinolone antibiotics, (ciprofloxacin, norfloxacin and ofloxacin), was compared with similar data for azithromycin and cefixime, each agent being examined by Prescription-Event Monitoring (PEM) during the early post-marketing period. 2. In PEM the exposure data are derived from general practitioner prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are provided by questionnaires (green forms) on which the prescribing medical practitioner records event data. When necessary, further information is obtained from a number of sources which include follow-up of all pregnancies and the patients' life-time medical record. 3. The main outcome measures were demographic information, including the patient's date of birth and sex; the indication for prescribing the drug being monitored; the reason for stopping treatment; the start and stop dates of treatment and the events recorded during and after treatment. 4. The final cohort for each of the five antibiotics exceeded 11000 patients. The only event significantly related to the use of all five antibiotics was nausea/vomiting. This was also the most frequent adverse event causing treatment to be discontinued with norfloxacin, ofloxacin and azithromycin (relevant information was not requested in the studies of ciprofloxacin and cefixime). Vaginal candidiasis was significantly more frequently associated with the use of the three 4-quinolones than with azithromycin and cefixime but it was frequently delayed until the week or two after the cessation of therapy. Within each event, as recorded in these studies, the highest event rates (the number of events per 1000 patients) in the week following the start of therapy were: 9.2 for diarrhoea with cefixime; 4.9 for nausea/vomiting with ofloxacin; 2.4 for rash with azithromycin; 2.2 for abdominal pain with norfloxacin; 1.5 for headache/migraine with ofloxacin; 1.4 for malaise/lassitude with ofloxacin; 1.2 for dizziness with norfloxacin. Uncommon events (reported in less than 1:1000 patients) included rare cases of allergic phenomena, convulsions and pseudomembranous colitis. There were no reports of tendinitis, tenosynovitis or tendon rupture in children but tendon disorders were reported in the two months following the start of treatment in 20 adults. A total of 307 pregnancies were reported. Thirty-eight of the 55 women who received these drugs during the first trimester of pregnancy gave birth to healthy babies. No congenital abnormalities were reported. Apart from one case of unconfirmed pseudomembranous colitis, none of the other 2468 deaths that occurred in these studies was attributed to the antibiotics. 5. These five antibiotics are acceptably safe antimicrobial agents when used in general medical practice. PEM is an effective method for monitoring the safety of recently introduced antimicrobial agents.

Adult↗
PubMed1995

Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring.

The incidence of vasodilation-related events (flushing, headache, dizziness and oedema) was determined in a total of 37,670 patients treated with diltiazem, nicardipine, isradipine or amlodipine and studied by Prescription-Event Monitoring between 1984 and 1991. Event rates are expressed as the percentage of patients who experienced these events during the six months after the first prescription. The rates for all these events with the newer vasoselective dihydropyridines (nicardipine, isradipine and amlodipine) were higher than those with diltiazem. Among the three dihydropyridines, there were large individual differences in the rates. With nicardipine, the frequency of each of the four vasodilation-related events were similar to one another (approximately 3%). With isradipine, the rates were also similar to one another but all were approximately twice those measured in the nicardipine study (approximately 6%). These differences may have been due to confounding factors such as the publicity about adverse drug reactions, the indication for use by individual patients or the doses actually being used at the time the event occurred. With amlodipine, in contrast, the rate for oedema was two to four times larger than the rates for flushing, headache or dizziness.

Adult↗
PubMed1995

Signalling drug-induced rash with 36 drugs recently marketed in the United Kingdom and studied by Prescription-Event Monitoring.

This study examines skin rash, as a reported event, in the patients who used one of the 36 drugs recently released to the UK market and studied by Prescription-Event Monitoring between 1985 and 1992. The results are also compared to the voluntary reports on rash as a possible adverse drug reaction sent to the Committee on Safety of Medicines (CSM). Specific types of skin rash (e.g. exfoliative dermatitis) are excluded. The rate of rash has been calculated for 2 periods, the first month (T1) and the subsequent 5 months (T2) after the first prescription for the drug. Despite the heterogeneity of the patient groups, the rate for rash between the 2nd and 6th months was consistent in the 36 drugs and probably represented the baseline rate of rash due to a variety of nonspecific causes. This rate (T2) was around 1 per 1,000 patients per month (ranging from 0.5 to 2 per 1,000 patients per month). On the other hand, in the first month after the first prescription for the drug, the rate (T1) varied substantially from 0.9 to 6.4 per 1,000 patients per month. Diltiazem had the highest first monthly rate. These rates are listed for the 36 drugs. The difference of the rates was tested by 2 methods: a standard statistical test assuming a Poisson model and a method based on the ratio of the rates for the 2 periods. When the 2 rates (T1 and T2) were similar to each other, drug induced rash was considered to be rare.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prescription-event monitoring of 10,401 patients treated with fluvoxamine.

Prescription-event monitoring (PEM) is one of two national systems of drug safety monitoring practised in Britain. The objective of this PEM study was to assess the safety of fluvoxamine and to monitor the occurrence of untoward and other events during treatment. A total of 10,401 patients treated with the drug in general practices throughout England were studied and data were analysed in the Drug Safety Research Unit, Southampton. The main outcome measures were the overall incidence of events per 1000 patients; the incidence during the first month of treatment; the mean incidence for months 2-6 of treatment; and the ratio of these rates as a signal that an event could be drug related. The most commonly reported category of events was neuropsychiatric while the most commonly reported individual events were nausea and vomiting. Fluvoxamine was shown to be a safe drug and no unexpected or previously undetected drug-related events were encountered. There was a relatively high incidence of gastro-intestinal symptoms, but other adverse reactions often encountered during treatment with tricyclic antidepressants were not frequently reported.

Adolescent↗
PubMed1993

Impact of electrical cardioversion for atrial fibrillation on left atrial appendage function and spontaneous echo contrast: characterization by simultaneous transesophageal echocardiography.

OBJECTIVES: This study assessed the function of the left atrial appendage in the pericardioversion period to gain insights into mechanisms involved in thromboembolism after cardioversion of atrial fibrillation. BACKGROUND: Systemic embolization associated with electrical cardioversion of atrial fibrillation is thought to originate from the left atrium or left atrial appendage, or both. However, the mechanism involved is poorly understood. METHODS: We studied left atrial appendage function with transesophageal echocardiography in 20 patients with atrial fibrillation before and after successful electrical cardioversion. We measured left atrial appendage emptying and filling velocities by pulsed wave Doppler echocardiography, characterized Doppler emptying patterns, measured atrial appendage areas and assessed the presence or absence of spontaneous echo contrast or thrombus. RESULTS: Organized left atrial appendage function returned in 16 (80%) of 20 patients immediately after cardioversion. Atrial appendage emptying velocities before cardioversion were greater in patients without (0.39 +/- 0.02 m/s) than in those with (0.25 +/- 0.12 m/s) spontaneous echo contrast (p = 0.045). Furthermore, emptying velocities before cardioversion were significantly greater than late diastolic emptying velocities after cardioversion (0.31 +/- 0.15 vs. 0.14 +/- 0.12 m/s, p = 0.0001), as well as in both the group with (0.25 +/- 0.12 vs. 0.13 +/- 0.13 m/s, p = 0.001) and the group without (0.39 +/- 0.02 vs. 0.15 +/- 0.12 m/s, p = 0.01) spontaneous echo contrast. In addition, left atrial and atrial appendage spontaneous echo contrast developed in 4 of 20 patients and increased in intensity in 3 of 20 patients in the immediate postcardioversion period. CONCLUSIONS: Organized left atrial appendage function returns in most patients immediately after cardioversion of atrial fibrillation. However, its function is impaired compared with that before cardioversion. Furthermore, spontaneous echo contrast increased in 7 (35%) of 20 patients after cardioversion. These observations suggest that stunned left atrial appendage function after cardioversion may predispose the chamber to thrombus formation, which may play a role in the mechanism involved in the occurrence of embolization after cardioversion.

Aged↗