Medicine safety in pregnancy and ambitions for the EU medicine regulatory framework.

Is the European Union (EU) regulatory framework concerning pregnant women and women at risk of becoming pregnant fit for the purpose? This article discusses improvements in how medicines should be developed and monitored for safe and effective use by pregnant women and women at risk of becoming pregnant.

Pregnancy losses in women with Type 1 or Type 2 diabetes in the UK: an investigation using primary care records.

AIM: This study aims to investigate pregnancy losses in women with Type 1 or Type 2 diabetes and compare this with the general population. METHODS: Pregnancies ending between 1993 and 2006 in those with Type 1 or Type 2 diabetes were identified on the General Practice Research Database. Pregnancy losses were identified from medical records and the cohort described by their characteristics and prescribing for diabetes. RESULTS: Of 2001 pregnancies identified in women with Type 1 diabetes, 678 ended in a pregnancy loss: 19.6% were spontaneous, 9.6% were induced and 4.3% were losses for unknown reasons. In women with Type 2 diabetes, there were 240 losses in 669 pregnancies: 21.1% were spontaneous, 10.3% induced and 4.0% were losses for unknown reasons. The proportion of spontaneous losses in women with diabetes was higher than in the general population (13.2%). Women with Type 1 diabetes treated with human and analogue insulins were 60% more likely to have a delivery than a loss (odds ratio 1.6, 95% CI 1.18-2.18) compared with human insulin treatment alone, although numbers were small. CONCLUSION: We found that the proportions of spontaneous losses in women with Type 1 or Type 2 diabetes were similar at approximately 20%, which is higher than in the general population and also higher than previous studies have reported. While much emphasis has been placed on pre-conception care for women with Type 1 diabetes, the same is now needed for those with Type 2 diabetes, given the similarity in outcomes and increasing prevalence of this condition.

Feasibility, reliability, and sensitivity to change of four radiographic scoring methods in patients with psoriatic arthritis.

OBJECTIVE: We set out to assess the feasibility, reliability, and sensitivity to change of 4 radiographic scoring methods in psoriatic arthritis (PsA). METHODS: Hand and feet radiographs from 50 patients with PsA were scored at 2 time points by 2 assessors with each of the following methods: modified Steinbrocker score, modified Sharp score (MSS), modified Sharp/van der Heijde score (SHS), and the Ratingen score for PsA. The radiographs of 10 patients were scored by both assessors to assess reliability using intraclass correlation coefficients (ICCs). Sensitivity to change was estimated using a standardized response mean (SRM) and smallest detectable change (SDC). RESULTS: The patients' mean ± SD age at baseline was 50 ± 12.1 years, the mean ± SD disease duration was 10 ± 8.4 years, and the mean ± SD followup period was 25 ± 9.6 months. Intrarater reliability was excellent for all methods (ICC >0.97). Interrater reliability was highest for the SHS (ICC 0.95-0.99). The percentage SDC for the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 2.9%, 2.1%, 1.4%, and 1.2%, respectively, and the SRMs were 0.46, 0.44, 0.77, and 0.79, respectively. The mean time to score each of the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 6.2, 10.5, 14.6, and 14.4 minutes, respectively. CONCLUSION: The SHS method was the most reliable and sensitive to change but took longer to perform. The Steinbrocker method is the most feasible but lacks the sensitivity of the SHS. The SDC of the Ratingen method is close to that of the SHS and MSS, but is quicker to perform.

Primary sclerosing cholangitis, Crohn's disease and HLA-B27 in black South African women.

Crohn's disease is rare in South African black people and primary sclerosing cholangitis (PSC) is also rare in black patients with IBD, from South Africa. The presence of HLA-B27 is generally associated with seronegative spondylo-arthropathies and correlates with the occurrence of ankylosing spondylitis, recurrent mouth ulcers and uveitis, in patients with IBD. We describe two women with the combination of Crohn's disease, PSC and HLA-B27 from our cohort of the last 5 years of three black patients with Crohn's disease. Crohn's disease, PSC and HLA-B27 respectively, occur rarely in black South Africans and their concurrent presence in two black women suggests a pathogenetic link of HLA-B27 between Crohn's disease and PSC in this population. Female gender might be an additional determinant in this setting.

Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma.

BACKGROUND: Ideally, intraoperative sentinel lymph node (SLN) analysis in breast cancer should be automated, have high concordance with extensive histopathology, and be applicable in any hospital setting. A prospective multicentre evaluation of the one-step nucleic acid amplification (OSNA) automated molecular diagnostic system of SLN analysis was undertaken. METHODS: Intraoperative examination of SLNs from 204 patients with breast cancer was performed by OSNA at four sites in the UK. Half of each SLN was assessed by OSNA (for cytokeratin 19 mRNA) and the remaining half was paraffin embedded for intensive histological examination at ten levels. Discordant cases were reanalysed by further molecular biological techniques and by additional histological examination of all remaining nodal material to ascertain whether the discordance was due to an uneven distribution of metastases, known as tissue allocation bias (TAB). RESULTS: After exclusion of samples affected by TAB, the overall concordance rate for OSNA versus histopathology was 96.0 per cent, with a sensitivity of 91.7 per cent and a specificity of 96·9 per cent. The median time to process a single SLN was 32 (range 22-97) min, and that for two nodes 42 (30-73) min. CONCLUSION: OSNA enables accurate automated intraoperative diagnosis and can be used successfully in different UK hospitals. When the SLN is shown to be positive, the patient can undergo immediate axillary clearance under the same anaesthetic rather than having a delayed second procedure.

Endometriosis and its coexistence with irritable bowel syndrome and pelvic inflammatory disease: findings from a national case-control study--Part 2.

OBJECTIVE: To investigate whether the increased chances of having a diagnosis of irritable bowel syndrome (IBS) and pelvic inflammatory disease (PID) in women with endometriosis is due to misdiagnosis or co-morbidity. DESIGN: A case-control study of women aged 15-55 years with endometriosis and matched controls. SETTING: Data from the UK's General Practice Research Database for the years 1992-2001. SAMPLE: A total of 5540 women aged 15-55 years, diagnosed with endometriosis, each matched to four controls without endometriosis. The index date was defined as the date of diagnosis. METHODS: Data were analysed to determine whether women with endometriosis were more likely to receive a diagnosis of PIDor IBS than women without endometriosis. Odds ratios were calculated for endometriosis associated with IBS and PID before and after the index date. MAIN OUTCOME MEASURES: Diagnosis of IBS or PID before and after the index date. RESULTS: Compared with the controls, women with endometriosis were 3.5 times more likely to have received a diagnosis of IBS (OR 3.5 [95% CI: 3.1-3.9]). Even after women had been diagnosed with endometriosis, they were still two and a half times more likely to receive a new diagnosis of IBS when compared with the controls (OR 2.5 [95% CI: 2.2-2.8]). Similarly, women with endometriosis were more likely than those without endometriosis to have been treated for PID both before (OR 5.9 [95% CI: 5.1-6.9]) and after (OR 3.8 [95% CI: 3.1-4.6]) being diagnosed with endometriosis. CONCLUSIONS: Women with endometriosis are more likely to be diagnosed with IBS and PID than controls, even after a definitive diagnosis of endometriosis has been reached.

Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study--Part 1.

OBJECTIVE: To determine the value of patient-reported symptoms in diagnosing endometriosis. DESIGN: A national case-control study. SETTING: Data from the UK General Practice Research Database for years 1992-2001. SAMPLE: A total of 5540 women aged 15-55 years, diagnosed with endometriosis, each matched to four controls without endometriosis. METHODS: Data were analysed to determine whether specific symptoms were highly indicative of endometriosis. Odds ratios for these symptoms were derived by conditional logistic regression analysis. MAIN OUTCOME MEASURES: Symptoms associated with endometriosis. RESULTS: The prevalence of diagnosed endometriosis was 1.5%. A greater proportion of women with endometriosis had abdominopelvic pain, dysmenorrhoea or menorrhagia (73%) compared with controls (20%). Compared with controls, women with endometriosis had increased risks of abdominopelvic pain (OR 5.2 [95% CI: 4.7-5.7]), dysmenorrhoea (OR 8.1 [95% CI: 7.2-9.3]), menorrhagia (OR 4.0 [95% CI: 3.5-4.5]), subfertility (OR 8.2 [95% CI: 6.9-9.9]), dyspareunia and/or postcoital bleeding (OR 6.8 [95% CI: 5.7-8.2]), and ovarian cysts (OR 7.3 [95% CI: 5.7-9.4]), and of being diagnosed with irritable bowel syndrome (IBS) (OR 1.6 [95% CI: 1.3-1.8]) or pelvic inflammatory disease (OR 3.0 [95% CI: 2.5-3.6]). Women with endometriosis were also found to consult the doctor more frequently than the controls and were twice as likely to have time off work. CONCLUSIONS: Specific symptoms and frequent medical consultation are associated with endometriosis and appear useful in the diagnosis. Endometriosis may coexist with or be misdiagnosed as pelvic inflammatory disease or IBS.

Risk of myocardial infarction in men and women with type 2 diabetes in the UK: a cohort study using the General Practice Research Database.

AIMS/HYPOTHESIS: Our primary aim was to establish reliable and generalisable estimates of the risk of myocardial infarction (MI) for men and women with type 2 diabetes in the UK compared with people without diabetes. Our secondary aim was to investigate how the MI risk associated with diabetes differs between men and women. METHODS: A cohort study using the General Practice Research Database (1992-1999) was carried out, selecting 40,727 patients with type 2 diabetes and 194,913 age and sex-matched patients without diabetes. Rates of MI in men and women with and without diabetes were derived, as were hazard ratios for MI adjusted for known risk factors. RESULTS: The rate of MI in men with type 2 diabetes was 19.74 (95% CI 18.83-20.69) per 1,000 person-years compared with 16.18 (95% CI 15.33-17.08) per 1,000 person-years in women with type 2 diabetes. The overall adjusted relative risk of MI in diabetes versus no diabetes was 2.13 (95% CI 2.01-2.26) in men and 2.95 (95% CI 2.75-3.17) in women and decreased with age in both sexes. Women with type 2 diabetes aged 35 to 54 years were at almost five times the risk of MI compared with women of the same age without diabetes (HR 4.86 [95% CI 2.78-8.51]). CONCLUSIONS/INTERPRETATION: This study has demonstrated that women with type 2 diabetes are at a much greater relative risk of MI than men even when adjusted for risk factors.

Systemic lupus erythematosus prevalence in the UK: methodological issues when using the General Practice Research Database to estimate frequency of chronic relapsing-remitting disease.

PURPOSE: The purpose of this study was to calculate the prevalence of systemic lupus erythematosus (SLE) between 1992 and 1998 using the General Practice Research Database (GPRD) METHODS: We identified all individuals who had contributed at least 3 years of data to the GPRD and who had a diagnosis of SLE with supporting evidence of their diagnosis. We calculated the annual age- and sex-specific prevalence of SLE. Additionally, we stratified the prevalence by years of data contributed to the GRPD. RESULTS: In males the point estimate of the prevalence of SLE increased from 7.5/100,000 (CI(95) 6.3, 8.8) to 10.1/100,000 (CI(95) 7.8, 12.2) but this rise was not statistically significant. However, prevalence appeared to increase significantly amongst females from 42.6/100,000 (CI(95) 39.6, 45.6) in 1992 to 70.8/100,000 (CI(95) 65.1, 76.6) in 1998. This increase was mainly amongst women aged 50-79 and in those contributing more than 5 years of data and could not be explained by increasing incidence of SLE or decreasing mortality during the study period. CONCLUSIONS: We found an increasing prevalence of SLE that could not be explained by increasing incidence or decreasing mortality. This is almost certainly an artefact caused by the increased likelihood of detecting or confirming cases of chronic relapsing-remitting diseases with increasing time contributed to the GPRD.

Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database.

AIMS/HYPOTHESIS: Risk estimates for stroke in patients with diabetes vary. We sought to obtain reliable risk estimates for stroke and the association with diabetes, comorbidity and lifestyle in a large cohort of type 2 diabetic patients in the UK. MATERIALS AND METHODS: Using the General Practice Research Database, we identified all patients who had type 2 diabetes and were aged 35 to 89 years on 1 January 1992. We also identified five comparison subjects without diabetes and of the same age and sex. Hazard ratios (HRs) for stroke between January 1992 and October 1999 were calculated, and the association with age, sex, body mass index, smoking, hypertension, atrial fibrillation and duration of diabetes was investigated. RESULTS: The absolute rate of stroke was 11.91 per 1,000 person-years (95% CI 11.41-12.43) in people with diabetes (n = 41,799) and 5.55 per 1,000 person-years (95% CI 5.40-5.70) in the comparison group (n = 202,733). The age-adjusted HR for stroke in type 2 diabetic compared with non-diabetic subjects was 2.19 (95% CI 2.09-2.32) overall, 2.08 (95% CI 1.94-2.24) in men and 2.32 (95% CI 2.16-2.49) in women. The increase in risk attributable to diabetes was highest among young women (HR 8.18; 95% CI 4.31-15.51) and decreased with age. No investigated comorbidity or lifestyle characteristic emerged as a major contributor to risk of stroke. CONCLUSIONS/INTERPRETATION: This study provides risk estimates for stroke for an unselected population from UK general practice. Patients with type 2 diabetes were at an increased risk of stroke, which decreased with age and was higher in women. Additional risk factors for stroke in type 2 diabetic patients included duration of diabetes, smoking, obesity, atrial fibrillation and hypertension.

Myocardial infarction risk and hormone replacement: differences between products.

OBJECTIVES: To establish the risk of myocardial infarction (MI) in users of hormone replacement therapy (HRT) compared with non-users and to compare the risk between different HRT regimens. METHODS: A population-based cohort and case-control study, and a case-control study nested within a cohort of HRT users, using the UK General Practice Research Database. Differences between HRT regimen, mode of administration and duration and recency of use were examined whilst adjusting for confounding. RESULTS: In the cohort and case-control study, 4537 cases of MI were identified in 2.62 million observed women years, cases were age-matched to 27,220 controls. In both studies, current and past HRT use were associated with reduced risk estimates for MI compared with no prior use. MIs were less likely to be fatal amongst women who had used HRT than amongst never users (OR(adj) 0.58; 95% CI 0.45-0.75). No difference in risk was seen between current and past use, oral and transdermal HRT or between different regimens (p>0.44). In the nested study, no difference was found in the association with MI risk between different oestrogen-progestogen combinations or between different combinations and tibolone. Unopposed oestrogen use was not associated with a decrease in risk compared with combined HRT. CONCLUSIONS: These results are consistent with previous observational studies in supporting the hypothesis that use of postmenopausal HRT is associated with a decrease in risk of acute myocardial infarction (AMI). Case fatality differed between HRT users and non-users, suggesting a protective effect of HRT. This study does not demonstrate a difference between regimens.

A drug utilisation study of antidepressants in children and adolescents using the General Practice Research Database.

AIMS: To characterise prescribing patterns of antidepressants (ATDs) to children and adolescents aged < or =18 years in the UK. METHODS: Subjects issued at least one ATD prescription between 1 January 1992 and 31 December 2001 were identified from the UK General Practice Research Database. Prescribing patterns, annual prevalence, morbidity patterns, and time to discontinuation of ATD use were identified. RESULTS: A total of 24,976 subjects received 93,091 prescriptions; 51,868 (55.7%), 38,429 (41.3%), and 2708 (2.9%) prescriptions were for tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and other ATDs respectively. ATD prevalence increased 1.7-fold from 1992 to 2001. TCA prevalence decreased by 30% from 3.6 to 2.5 per 1,000; SSRI prevalence increased 10 times from 0.5 to 4.6 per 1,000. In new ATD users aged < or =10 years, the most common diagnosis associated with TCA use was nocturnal enuresis (75.1%); in those aged > or =15 years, it was depression (45.8%). Depression was also associated with SSRI use (69.0%). For new users with depression, the median treatment durations for TCAs and SSRIs were 30 and 58 days respectively. TCA users were more likely to terminate treatment than SSRI users (TCAs v fluoxetine: 1.40, 95% CI 1.32 to 1.47; non-fluoxetine SSRIs v fluoxetine: 1.01, 95% CI 0.96 to 1.07). CONCLUSIONS: SSRIs have gained popularity for the treatment of depression compared with TCAs. TCAs are still used despite their lack of efficacy in prepubertal depression and their moderate effect in adolescents. However, >50% of subjects discontinue treatment after two months, with TCA users stopping earlier than SSRI users.

Venous thromboembolism associated with cyproterone acetate in combination with ethinyloestradiol (Dianette): observational studies using the UK General Practice Research Database.

PURPOSE: To derive risk estimates for venous thromboembolism (VTE) in women prescribed cyproterone acetate combined with ethinyloestradiol (CPA/EE), a drug licensed in the UK for the treatment of women with acne or hirsutism. CPA/EE provides a treatment option for women with polycystic ovary syndrome (PCOS). CPA/EE has been associated with an increased risk of VTE. METHODS: Using the General Practice Research Database, we conducted cohort and case-control analyses in all women aged 15-39 and then nested in a population of women of the same age with acne, hirsutism or PCOS. RESULTS: The incidence rate ratio (IRR) for VTE in women exposed to CPA/EE versus conventional combined oral contraceptives (COCs) was significantly raised (all women: 1.92; 95% CI: 1.22,2.88; nested: 2.51; 95% CI: 1.07,5.75). Using exposure to conventional COCs as the reference, the adjusted odds ratio (ORadj) for VTE associated with CPA/EE was 1.45 (95% CI: 0.80,2.64) in all women and 1.71 (95% CI: 0.31,9.49) in women with acne, hirsutism or PCOS. CONCLUSIONS: The risk of VTE associated with CPA/EE use does not differ significantly from that associated with the use of conventional COCs. These data are reassuring and together with knowledge of the risks associated with other treatments for acne, in particular, should influence prescribing practice.

Utilisation of hormone replacement therapy in the United Kingdom. A descriptive study using the general practice research database.

OBJECTIVE: To determine prevalence and patterns of hormone replacement therapy (HRT) utilisation in women in the UK. DESIGN: Prospective observational study. SETTING: UK general practice. POPULATION: Women from general practices throughout the UK. METHODS: The study period was 1 January 1992 to 31 December 1998. Age-specific prevalence was calculated for each year. Trends in prescribing patterns were described over time. A sub-cohort of 'new starters' on HRT was identified to establish patterns of use, including duration of use and switching of preparations. Characteristics of the sub-cohort were compared with a reference group of non-HRT users. MAIN OUTCOME MEASURES: Prevalence, prescribing patterns and differences in characteristics between HRT users and non-HRT users. RESULTS: Among women aged 45-64, prevalence of HRT use increased from 18.6% in 1992 to 27.7% in 1998. Secular trends were observed away from prescribing combined-sequential preparations and towards use of combined-continuous preparations. Among the prescriptions for combined HRT products, only 4.3% contained medroxyprogesterone acetate (MPA). A total of 45.7% of women without a record of a hysterectomy and 53.8% of women with a record of a hysterectomy used HRT for at least three years. When women were partitioned by year of starting HRT, there was a trend of increasing duration of use across the seven years. Some women without a record of a hysterectomy were receiving unopposed oestrogen without progestogen supplementation. CONCLUSIONS: Within the past decade, use of HRT has increased among women in the UK with large numbers of women using HRT for long periods and treatment often tailored to the individual.

The risk of liver disorders in women prescribed cyproterone acetate in combination with ethinyloestradiol (Dianette): a nested case-control study using the GPRD.

PURPOSE: To explore the risk of liver disorders associated with cyproterone acetate combined with ethinyloestradiol (CPA/EE). CPA/EE is licensed in the UK for the treatment of women with acne and hirsutism and is a treatment option for polycystic ovary syndrome (PCOS). It acts as a contraceptive also. METHODS: Using the General Practice Research Database, we conducted a cohort analysis and case-control study in women aged 15-39 with acne, hirsutism or PCOS to estimate the risk of liver disorders associated with CPA/EE. RESULTS: Compared with cases exposed to conventional combined oral contraceptives (COCs), the age-adjusted incidence rate ratio for liver disorders in women using CPA/EE was 1.7 (95% CI: 0.9, 3.4) and compared with no use it was 1.5 (95% CI: 0.8, 2.8). In the case-control study, the adjusted odds ratio (OR) for liver disorders in women exposed to CPA/EE was 1.6 (95% CI: 0.7, 3.5) and 0.8 (95% CI: 0.5, 1.3) for exposure to conventional COCs, compared with no use. The risk of liver disorders in women prescribed CPA/EE was not significantly greater than that in women prescribed conventional COCs (OR: 2.1 [95% CI: 0.9, 4.8]). CONCLUSION: Our results do not indicate an increased risk for liver disorders associated with CPA/EE use in women with acne, hirsutism or PCOS after adjusting for potential confounding. This may be due to lack of statistical power.

Differences in the use of combined oral contraceptives amongst women with and without acne.

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) provides a treatment option for women with acne, hirsutism or polycystic ovary syndrome (PCOS). CPA/EE may be prescribed as an oral contraceptive (OC), but is not licensed as such in the UK. The use of CPA/EE steadily increased after its introduction to the UK market in 1987, but there was a marked increase in its share of the OC market after 1995. METHODS: Using the General Practice Research Database, utilization patterns of CPA/EE and conventional oral contraceptives were compared in women aged 15-39 years, with or without acne or PCOS. RESULTS: Between 1994 and 1998, CPA/EE accounted for an increasing proportion of all OC use. The proportion of CPA/EE prescribed to women with acne declined between 1994 and 1998, whereas that prescribed to women with PCOS remained constant. The age-specific use of CPA/EE by women with acne or PCOS almost doubled. After 1995, there was a marked increase in the use of products containing levonorgestrel by women with acne or PCOS. CONCLUSIONS: A large proportion of CPA/EE is prescribed to women with acne and/or PCOS, although this proportion decreased between 1992 and 1998. This has important implications in CPA/EE risk assessment studies.

The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.

Concomitant prescribing of benzodiazepines during antidepressant therapy in the elderly.

A follow-up study was performed in two ambulatory cohorts aged > or =65 to investigate whether the prevalence and incidence of anxiolytic/hypnotic benzodiazepine drug prescribing is comparable between users of serotonin reuptake inhibitors (SSRIs) and users of tricyclic antidepressants (TCAs). The prevalence and incidence of benzodiazepines during antidepressant therapy was estimated among users of TCAs and SSRIs. Coprescribing of benzodiazepines occurred in 53% of the TCA users and 57% of the SSRI users (prevalence RR 1.1; CI(95) 0.9-1.2). The average duration of benzodiazepine drug use was >65 days per 100 days of antidepressant use. During SSRI therapy, significantly more people started benzodiazepine drug therapy than during TCA therapy (incidence rate ratio (RR) 1.7; CI(95) 1.2-2.4). Analyses repeated 5 years later yielded similar results (overall incidence RR(MH) 1.6; CI(95) 1.3-2.0). These data indicate that SSRI use is associated with a significantly higher chance of starting benzodiazepines compared with TCA use.

Prescribing of gastroprotective drugs among elderly NSAID users in The Netherlands.

BACKGROUND: Use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of gastrointestinal toxicity, in particular when risk factors are present. METHODS: A study was performed to investigate concomitant prescribing of gastroprotective agents (H2-receptor antagonists, proton pump inhibitors, or misoprostol) in an ambulatory cohort of NSAID users aged 65 years and over. The prevalence of concomitant prescribing was studied, as well as the prophylactic prescribing of gastroprotective drugs. A stepwise logistic regression was performed to determine predictive variables of prophylactic and concomitant gastroprotective drug prescribing. RESULTS: Co-prescribing of gastroprotective drugs occurred in 1522 (23%) (of which 944 concerned prophylactic prescribing) of the NSAID users (n = 6557), with an average duration of 67 days per 100 days of NSAID use. Co-prescribing of gastroprotective drugs varied among individual NSAIDs. Concomitant use of oral corticosteroids (ORadj 2.4; Cl95 2.0-2.9), coumarins (ORadj 1.6; Cl95 1.3-2.0), and low dose aspirin (ORadj 1.6; Cl95 1.4-1.9) were significantly associated with both prophylactic and concomitant prescribing of gastroprotective agents during NSAID therapy. DISCUSSION: Despite current guidelines recommending gastroprotective drug prescribing among high risk groups, the rate of concomitant prescribing of gastroprotective agents in NSAID users aged 65 years and over is low. Feedback to prescribers should be given to improve prescribing practices in this high risk group.

Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data.

AIMS: The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. METHODS: During 1991-98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. RESULTS: Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. CONCLUSIONS: Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings.