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Biomedical subjects

R D Farmer

Publications and source records attributed to R D Farmer.

At least 19 recordsLinked to original sources
PubMed2001

Evaluating adverse cardiovascular effects of drug treatment for benign prostatic hyperplasia (BPH): methodological considerations.

When studying the effects of drug exposure in diseases with a long asymptomatic clinical course, exposure classification may be biased by the gradually developing "visibility" of the disease. Benign prostatic hyperplasia (BPH) is such a disease. We found that cardiovascular morbidity is two times more prevalent in patients starting drug treatment for BPH when compared to age-matched population controls. This resulted in a difference of cardiovascular prognostic factors between the exposed and non-exposed. This feature can jeopardize the validity of non-randomized comparisons of drug effects. Moreover, the existence of non-treatment strategies, disease under-reporting, and an elderly population with a high baseline risk of experiencing (cardiovascular) outcome events were encountered as methodological problems. When studying adverse cardiovascular effects in patients using BPH products in a non-randomized fashion, an important question is whether we can measure in the database all relevant prognostic factors and use the information for statistical adjustment. This question is an important challenge to observational research and once again stresses the need for control of possible biases in choosing an appropriate study design.

5-alpha Reductase Inhibitors↗
PubMed2001

Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database.

OBJECTIVE: To determine the incidence of venous thromboembolism in pregnancy and the puerperium and to identify risk factors for pregnancy-related venous thromboembolism. DESIGN: Cohort study and case-control study. SETTING: London, UK. POPULATION: 395,335 women with live births or pregnancies of 24 or more weeks of gestation between 1988 and 1997. METHODS: Data extraction from the St Mary's Maternity Information System database. Random sample of 5% for case-control study. MAIN OUTCOME MEASURES: Incidence of venous thromboembolism; odds ratios for variables associated with venous thromboembolism. RESULTS: The incidence of venous thromboembolism was 85/100,000 maternities. There were approximately twice as many postpartum as antepartum events. Blood group A, multiple pregnancy, caesarean section, cardiac disease, delivery at gestational age of < 36 weeks, a body mass index of > or = 25, or more and maternal age of 35 or over were all found to increase incidence of venous thromboembolism. CONCLUSIONS: Although venous thromboembolism is the leading cause of maternal deaths in the UK, it is still a rare event. Most of these events are deep vein thromboses occurring in the postpartum period. Antenatally multiple birth is an important risk factor. Postnatally women who have had a caesarean section, premature delivery or history of cardiac disease should be assessed carefully for venous thromboembolism.

Adult↗
PubMed2001

Lower urinary tract symptoms suggestive of benign prostatic obstruction--Triumph: the role of general practice databases.

The Triumph project aims to document the current management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in general practice and to assess the effectiveness of the initial treatment options used. The first phase of the project will consider existing data sources in primary care. A patient's medical record will contain most, if not all, clinically relevant information, and databases combining the records from a network of computerised general practices can provide longitudinal data for complete populations, linking prescribing records to clinical information on disease progression and outcomes for individual patients. Database research can provide rapid information and offers the ability to conduct studies on a scale that would previously have been prohibited by both time and expense. Within the Triumph project, the THALES, General Practice Research Database (GPRD) and Integrated Primary Care Information (IPCI) databases are, or will be, used to examine the current management of LUTS/BPH in France, the UK and the Netherlands respectively. Preliminary results from the UK General Practice Research Database (GPRD) showed that LUTS/BPH incidence increased linearly from the ages of 45 to 85 years (r(2) = 0.992) and prevalence increased from 3.5% to 35% for men in their late 40s and 80s respectively. With treatment failure defined as a change to another medical therapy, catheterisation or prostatic surgery, and accounting for age and year variation, patients receiving the older alpha(1)-blockers (indoramin and prazosin) appeared to fail significantly earlier than those receiving finasteride. There was no significant difference between finasteride and the newer alpha(1)-blockers (tamsulosin, alfuzosin, terazosin and doxazosin). Patterns of changes between products from the THALES database in France were broadly similar to those seen in the UK.

Databases, Factual↗
PubMed2001

The risk of liver damage associated with minocycline: a comparative study.

Using the General Practice Research Database, the authors performed (1) a cohort analysis comparing the incidence of liver dysfunction in new users of minocycline with new users of oxytetracycline/tetracycline and (2) a case control study assessing antibiotic exposure in new cases of liver dysfunction and controls without liver dysfunction. In new users, the incidence of liver dysfunction in those exposed to minocycline was 1.04 cases/10,000 exposed person months (EPM) and 0.69 cases/10,000 EPM in those exposed to oxytetracycline/tetracycline (relative risk 1.51 [CI95: 0.63, 3.65]). The risk in both groups was greatest in the first month of use. The adjusted odds ratio (ORadj) of liver dysfunction associated with exposure to minocycline compared with nonuse was 2.10 (CI95: 1.30, 3.40); for oxytetracycline/tetracycline, the ORadj was 1.46 (CI95: 0.81, 2.64); and for exposure to erythromycin, the ORadj was 1.64 (CI95: 0.71, 3.80). The authors thus support a weak association between the use of oral antibiotics and liver dysfunction in patients with acne. The risk associated with exposure to minocycline appears to be very small. The cohort analysis demonstrated that any risk associated with minocycline was not significantly greater than that associated with oxytetracycline/tetracycline exposure.

Adolescent↗
PubMed2000

The treatment of depression in UK general practice: selective serotonin reuptake inhibitors and tricyclic antidepressants compared.

BACKGROUND: Antidepressants are commonly prescribed by general practitioners as treatment for depression. Controversy exists as to the effectiveness in everyday use of the older tricyclic antidepressants (TCAs) when compared to the newer selective serotonin reuptake inhibitors (SSRIs). AIM: To investigate the patterns of current prescribing of antidepressants for the treatment of depression and compare TCAs with the newer SSRIs. METHOD: The study population was patients attending 151 computerised general practices from throughout the United Kingdom between 1991 and 1996. Patients with new prescriptions for antidepressants and a diagnosis of depression were identified. Age and gender distributions, prescribed doses and drop-out rates were investigated. RESULTS: During the study period 9.8% of patients received a prescription for an antidepressant, there was a 40% increase in the prescribing rate of TCAs and a 460% increase in SSRI prescribing. TCAs were initially prescribed in sub-therapeutic doses. More than 50% of patients ceased taking their antidepressants within 6 weeks of starting treatment. Fluoxetine and paroxetine were more likely to be prescribed for a therapeutic period than were other antidepressants. CONCLUSIONS: General practitioners should prescribe a therapeutic dose of antidepressant for a recognised therapeutic period to ensure that patients with depression receive the most effective treatment.

Adolescent↗
PubMed2000

A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives.

AIMS: In October 1995 in response to the results of three studies, the Committee on the Safety of Medicines advised doctors and pharmacists that oral contraceptives containing desogestrel (DSG) and gestodene (GST) were associated with around a two-fold increase in the risk of thromboembolism compared with those containing other progestogens. The objective of this study was to estimate the risk of idiopathic venous thromboembolic disease (VTE) in users of combined oral contraceptives (COCs), to compare the risk between formulations and to examine the effect of using age banding as opposed to matching by exact year of birth. METHODS: A nested case control study was conducted using the General Practice Research Database. Women with a VTE event recorded between 1992 and 1997, who were treated with an anticoagulant, from consideration of their prescription records were likely to have been using a COC prescription on the day of the event and also had no exclusion factors, were deemed cases. For comparison with the previous studies, two nested case control studies were undertaken. Study 1 used controls matched by practice and year of birth. Study 2 used controls matched by practice and within 5 years age bands. RESULTS: We found an incidence of idiopathic VTE amongst users of combined oral contraceptives of 3.8 per 10 000 exposed women years. Incidence rates increased markedly after 35 years of age. The nested case-control study using controls matched by year of birth showed no significant difference in risk between the major COC formulations. With levonorgestrel (LNG) 150 microgram and ethinyloestradiol (EE) 30 microgram as the reference, the adjusted ORs for GST 75 microgram and EE 30 microgram was 1.3 (95% CI 0.8, 2.1), for DSG 150 microgram and EE 30 microgram it was 1.0 (95% CI 0.7, 1.7) and for DSG 150 microgram and EE 20 microgram it was 0.8 (95% CI 0.4, 1.6). Using less rigorous matching criteria, matching controls to cases within 5 years age bands, the ORs increased. When a mixed group of COCs, characterized by having LNG as the progestogen component was used as the reference category, there was an elevation in the ORs for the newer products. We found a significant association between idiopathic VTE and current smoking (OR 2.0 (1.4, 2.7)), BMI over 35 (OR 3.8 (1.8, 8.0)) and asthma (OR 1.9 (1.3, 2.9)). The OR for women who had proxy evidence of general ill health (indicated by the number of prescriptions issued) was 2.2 (1.7, 3.7). CONCLUSIONS: The results of this study indicate that a number of the characteristics of the women taking COCs affect the risk of VTE. There is no evidence to support the hypothesis that there is any difference in risk between COC formulations containing under 50 microg ethinyloestradiol.

Adolescent↗
PubMed2000

Validation of the diagnosis of venous thromboembolism in general practice database studies.

AIMS: The study was conducted to determine whether the method for selecting cases of venous thromboembolism (VTE) from general practice databases significantly affected the findings of an epidemiological study. METHODS: Cases of VTE were identified from the UK General Practice Research Database (GPRD) by searching for codes for deep vein thrombosis (DVT) and pulmonary embolism (PE). These had to be supported by evidence of anticoagulation and be exposed to a combined oral contraceptive (COC) at the time of the event. Additional information about the event was sought from general practitioners who were requested to complete a questionnaire and to supply anonymised copies of hospital letters and discharge summaries. RESULTS: Of the 285 cases identified from the GPRD, additional information was available for 177 VTE events. This information showed that 84% of those events were supported by hospital investigations or a death certificate. Using only verified cases, rather than all GPRD identified events, did not alter the results of the epidemiological study. CONCLUSIONS: The GPRD provides information of sufficiently high quality to allow valid epidemiological research of VTE events. Excluding cases without a database record of hospital admission would lead to valid events being overlooked, and an under-estimate of the disease incidence.

Adult↗
PubMed2000

The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives.

OBJECTIVES: To investigate the factors associated with idiopathic venous thromboembolism in combined oral contraceptive users and to estimate the crude and age-specific incidence rates ofidiopathic venous thromboembolism among this population. METHODS: The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives. Cohort and nested case-control studies were carried out using the same methodology on both databases. We conducted a meta-analysis using the individual data for the cases and controls from the two case-control studies to identify factors associated with idiopathic venous thromboembolism in women using combined oral contraceptives. RESULTS: The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100,000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m2 and over, the association rising dramatically in women with a body mass index of 35 kg/m2 or more; smoking; general ill health; and asthma. CONCLUSION: We believe that, before prescribing combined oral contraceptives, the venous as well as the arterial factors need to be considered and, in addition, age, obesity and smoking are all relevant when assessing an individual patient's risk.

Adolescent↗
PubMed2000

Medical therapy for benign prostatic hyperplasia: a review of the literature.

OBJECTIVE: To review the existing evidence regarding the efficacy and safety of medical therapy for lower urinary tract symptoms (LUTS) indicative of benign prostatic hyperplasia (BPH). To assess randomised controlled trials investigating the six alpha-adrenergic receptor antagonists (alpha-blockers), prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin, that benefit patients by relaxing prostatic smooth muscle, and the anti-androgen, finasteride, that mediates its more long-term benefits by reducing prostate size. RESULTS: This review suggests that both classes of drug offer significant improvement in criteria used to evaluate symptomatic BPH and can be effective whilst being acceptably safe. Furthermore, the therapeutic efficacy of all contemporary alpha-blockers appear similar, both in terms of symptom relief and urodynamic improvements. Randomised controlled trials have additionally demonstrated that finasteride therapy can provide improvement in terms of quality of life indices, prostate volume, and risks of progressing to acute urinary retention or prostatic surgery. While alpha-blockers have a rapid onset of action, likely to produce a therapeutic result within weeks, regardless of whether prostatic enlargement or bladder outlet obstruction is present, finasteride appears to be effective for more long-term therapy for up to 4 years, but only in alleviating symptoms when they are associated with a significantly large prostate. Neither finasteride nor the alpha(1a)-receptor-selective blocker, tamsulosin, are associated with the lowering of blood pressure and incidence of cardiovascular side effects that are apparent with other less selective alpha-blocker therapies such as dizziness and postural hypertension. They are, however, both associated with an increased risk of sexual dysfunction, albeit less than those associated with surgical intervention. Whereas tamsulosin is associated only with ejaculatory dysfunction, finasteride is additionally linked to decreased libido and impotence.

Adrenergic alpha-Antagonists↗
PubMed2000

How do symptoms indicative of BPH progress in real life practice? The UK experience.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are usually, but not exclusively associated with benign prostatic hyperplasia (BPH). Using a population identified from the UK General Practice Research Database (GPRD), we describe the changes in the management of LUTS/BPH and assess the effectiveness of medical therapy between 1992 and 1998. METHODS: 61,364 men with LUTS/BPH and without a record of prostatic cancer were identified on the database. 14,195 were treated with an alpha1-blocker or finasteride. Treatment failure was defined as prostatic surgery, catheterisation or a switch in medical therapy. RESULTS: LUTS/BPH incidence increased linearly from the age of 45 to 85 years (r2 = 0.992) and prevalence increased from 3.5% to 35% for men in their late 40s and 80s respectively. Prostatectomy rates increased linearly from the age of 50 to 80 years (r2 = 0.984). Between 1992 and 1998, total treated-patient time had increased 3-fold, patients have been medically treated earlier and have increasingly been prescribed the LUTS/BPH-specific treatments finasteride, tamsulosin and alfuzosin in comparison to older treatments (indoramin, prazosin). In parallel, there has been a progressive increase in the interval between first diagnosis and prostatic surgery, and this interval is significantly longer for medically treated patients than those receiving no medical therapy. The intervals between the start and failure of medical therapy were significantly shorter for patients receiving indoramin and prazosin than for those receiving specific LUTS/BPH treatments. CONCLUSIONS: Between 1992 and 1998 there has been a significant lengthening of the period between first diagnosis of LUTS/BPH and surgery. This postponement of surgery is associated with earlier treatment and the increased use of specific LUTS/BPH treatments that appear more effective than older products in delaying treatment failure.

Aged↗
PubMed2000

Liver damage associated with minocycline use in acne: a systematic review of the published literature and pharmacovigilance data.

OBJECTIVE: Minocycline is an antibacterial drug used in the treatment of acne. Concern has been expressed over the possibility of severe adverse reactions to minocycline, including hepatitis. This study set out to identify and characterise reported cases of hepatotoxicity associated with the use of minocycline. METHODS: A systematic review of the literature including a search of computerised databases and analysis of data from the Uppsala Monitoring Centre (WHO Collaborating Centre for International Drug Monitoring) was conducted. The review involved a search for original case reports involving liver damage in people using minocycline. Patients taking minocycline for reasons other than acne or those given intravenous minocycline were excluded. The search strategy involved an enquiry of computerised databases and a search for secondary references. Cases were then classified appropriately. RESULTS: 65 reported cases of hepatitis or liver damage in association with minocycline from either case reports or case series were identified from the literature review. 58% of cases occurred in females and 94% were aged under 40 years. For 20 case reports there was insufficient information to classify the type of event, but for the remaining 45, 2 types of hepatic reaction were recognised: autoimmune hepatitis associated with lupus-like symptoms occurring after a median duration of exposure to minocycline of 365 days in females (n = 20) and 730 days in males (n = 9), hypersensitivity reaction associated with eosinophilia and exfoliative dermatitis occurring within 35 days of therapy (n = 16). Reports to the WHO of hepatic adverse drug reactions associated with minocycline accounted for 6% (493) of all minocycline-related adverse drug reactions (8025). The pattern of distribution in relation to exposure demonstrated 2 groups, similar to that described by the case reports. CONCLUSIONS: Severe cases of minocycline-associated hepatotoxicity appear to be a hypersensitivity reaction and occur within a few weeks of commencing therapy. An autoimmune hepatitis usually presents after exposure to minocycline of a year or more, is more common in women and is sometimes associated with lupus-like symptoms.

Adolescent↗
PubMed1999

Venous thromboembolic disease and combined oral contraceptives: A re-analysis of the MediPlus database.

In October 1995 the Committee on Safety of Medicines advised UK doctors and pharmacists that oral contraceptives containing desogestrel and gestodene were associated with double the risk of venous thromboembolic events (VTE) compared to pills containing other progestogens. In 1997 data was analysed from the MediPlus database of UK general practitioner records, which reported odds ratios for desogestrel and gestodene lower than that for levonorgestrel. Here the results of a more stringent nested case control analysis on the MediPlus database are reported. The study was larger and cases were verified. A crude incidence of idiopathic VTE was found amongst users of combined oral contraceptives of 4.6 per 10 000 exposed women years. Using levonorgestrel 150 microg + ethinyloestradiol 30 microg as reference, non-significant odds ratios of 1.1 (0.5-2.6) for desogestrel 150 microg + ethinyloestradiol 30 microg and 1.1 (0.5-2.4) for gestodene 75 microg + ethinyloestradiol 30 microg were found. The results of this study show no significant difference in risk between different formulations of combined oral contraceptive.

Adolescent↗
PubMed1998

The risks of venous thromboembolic disease among German women using oral contraceptives: a database study.

This study investigated the risk of venous thromboembolic disease (VTE) between second and third generation combined oral contraceptives, using the German MediPlus database of patient records. Women studied included 42 patients between the ages of 18 and 49 years, with a diagnosis of VTE treated with an anticoagulant, who were exposed to an oral contraceptive (OC). Four controls per patient (168), matched by year of birth and exposure to an OC on the even day, were identified. More women were users of second generation than third generation OC, and none were using progestogen-only pills. There was no significant difference between patients and control subjects with respect to the type of OC used on the event day (unadjusted odds ratio for third versus second generation users was 0.77; 95% confidence interval [CI] 0.38-1.57). There was no significant age difference between second and third generation users among patients or control subjects. Between January 1 and the event date, there was no significant difference between the patients and control subjects in terms of the number of oral contraceptive prescriptions, number of consultations for psychotherapeutic complaints, or mixed physical and psychotherapeutic consultations; however, patients did demonstrate significantly more consultations for purely physical complaints compared with control subjects (p < 0.0001). There were no significant consultation differences between patients with pulmonary emboli (n = 6) and other VTE patients (n = 36). No significant differences with respect to VTE risk between users of second and third generation oral contraceptives were found in this study. Consultations (physical) for patients were higher than for control subjects before the VTE event. If consultation rate relates to the general health status of a person, this might indicate that VTE risk is higher among women of poorer health, but that this is not related to the type of progestogen in the oral contraceptive that they use.

Adolescent↗
PubMed1998

Oral contraceptives and venous thromboembolic disease: the findings from database studies in the United Kingdom and Germany.

OBJECTIVE: Three research articles published in late 1995 and early 1996 suggested that oral contraceptives containing either of the newer progestogens (gestodene or desogestrel) could be associated with an increased risk of venous thromboembolism. During the months after the initial publications, the results have been scrutinized with great care and further studies have been published. The findings of 2 recent database studies, 1 in the United Kingdom and 1 in Germany, are presented in this article. PATTERNS OF USE: The average age of users of combined oral contraceptives in Germany was 27 years, compared with 26 years in the United Kingdom. In Germany the use of gestodene-based products was lower than that in the United Kingdom. In the United Kingdom the users of desogestrel with 20 microg ethinyl estradiol (Mercilon) were older than the users of desogestrel with 30 microg ethinyl estradiol (Marvelon). CRUDE INCIDENCE: The crude incidence of venous thromboembolism in the UK study was 4.1 cases/10,000 woman-y exposure to combined oral contraceptives. In Germany it was 4.2 cases/10,000 woman-y. In Germany the rates among users of second-generation combined oral contraceptives were higher than those among users of third-generation products. The reverse was the case in the United Kingdom. In the United Kingdom the crude incidence rates were higher for the 20 microg estrogen desogestrel product than for the 30 microg product. CASE-CONTROL ANALYSIS: The adjusted odds ratios in the UK study did not show significant increases for desogestrel or gestodene compared with levonorgestrel products. There were inconsistencies in the results among centers in the 2 international studies (the World Health Organization and Transnational studies). In both there was a consistent inverse dose-response relationship with estrogen in all centers. CONCLUSION: The limitations of the observational studies are such that the hypothesis that the newer progestogens are more likely to cause venous thromboembolism cannot be proved.

Adult↗
PubMed1997

Population-based study of risk of venous thromboembolism associated with various oral contraceptives.

BACKGROUND: Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies. METHODS: We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540,000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease. FINDINGS: 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens. INTERPRETATION: The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 micrograms ethinyloestradiol and desogestrel compared with the 30 micrograms product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding.

Adolescent↗