ContextPsoriasis is the most common T-helper cell type 1 (TH1) immunological disease. Evidence has linked TH1 diseases to myocardial infarction (MI). Psoriasis has been associated with cardiovascular diseases, but has only been investigated in hospital-based studies that did not control for major cardiovascular risk factors.ObjectiveTo determine if within a population-based cohort psoriasis is an independent risk factor for MI when controlling for major cardiovascular risk factors.Design, Setting, and PatientsA prospective, population-based cohort study in the United Kingdom of patients with psoriasis aged 20 to 90 years, comparing outcomes among patients with and without a diagnosis of psoriasis. Data were collected by general practitioners as part of the patient's medical record and stored in the General Practice Research Database between 1987 and 2002, with a mean follow-up of 5.4 years. Adjustments were made for hypertension, diabetes, history of myocardial infarction, hyperlipidemia, age, sex, smoking, and body mass index. Patients with psoriasis were classified as severe if they ever received a systemic therapy. Up to 5 controls without psoriasis were randomly selected from the same practices and start dates as the patients with psoriasis. A total of 556 995 control patients and patients with mild (n = 127 139) and severe psoriasis (n = 3837) were identified.Main Outcome MeasureIncident MI.ResultsThere were 11 194 MIs (2.0%) within the control population and 2319 (1.8%) and 112 (2.9%) MIs within the mild and severe psoriasis groups, respectively. The incidences per 1000 person-years for control patients and patients with mild and severe psoriasis were 3.58 (95% confidence interval [CI], 3.52-3.65), 4.04 (95% CI, 3.88-4.21), and 5.13 (95% CI, 4.22-6.17), respectively. Patients with psoriasis had an increased adjusted relative risk (RR) for MI that varied by age. For example, for a 30-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.29 (95% CI, 1.14-1.46) and 3.10 (95% CI, 1.98-4.86), respectively. For a 60-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.08 (95% CI, 1.03-1.13) and 1.36 (95% CI, 1.13-1.64), respectively.ConclusionsPsoriasis may confer an independent risk of MI. The RR was greatest in young patients with severe psoriasis.

https://jamanetwork.com/journals/jama/articlepdf/203598/JOC60135.pdf

Risk of myocardial infarction in patients with psoriasis.

Treatment with systemic corticosteroids is known to increase the risk of fractures but little is known of the fracture risks associated with inhaled corticosteroids. A retrospective cohort study was conducted using a large UK primary care database (the General Practice Research Database [GPRD]). Inhaled corticosteroid users aged 18 years or older were compared with matched control patients and to a group of noncorticosteroid bronchodilator users. Patients with concomitant use of systemic corticosteroids were excluded. The study comprised 170,818 inhaled corticosteroid users, 108,786 bronchodilator users, and 170,818 control patients. The average age was 45.1 years in the inhaled corticosteroid, 49.3 years in the bronchodilator, and 45.2 years in the control groups. In the inhaled corticosteroid cohort, 54.5% were female. The relative rates (RRs) of nonvertebral, hip, and vertebral fractures during inhaled corticosteroid treatment compared with control were 1.15 (95% CI, 1.10-1.20), 1.22 (95% CI, 1.04-1.43), and 1.51 (95% CI, 1.22-1.85), respectively. No differences were found between the inhaled corticosteroid and bronchodilator groups (nonvertebral fracture RR = 1.00; 95% CI, 0.94-1.06). The rates of nonvertebral fractures among users of budesonide (RR = 0.95; 95% CI, 0.85-1.07) and fluticasone propionate (RR = 1.03; 95% CI, 0.71-1.49) were similar to the rate determined for users of beclomethasone dipropionate. We conclude that users of inhaled corticosteroids have an increased risk of fracture, particularly at the hip and spine. However, this excess risk may be related more to the underlying respiratory disease than to inhaled corticosteroid.

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Use of oral corticosteroids and risk of fractures.

A review of uses of health care utilization databases for epidemiologic research on therapeutics

Aims/hypothesis The risk of developing a range of solid tumours is increased in type 2 diabetes, and may be influenced by glucose-lowering therapies. We examined the risk of development of solid tumours in relation to treatment with oral agents, human insulin and insulin analogues. Methods This was a retrospective cohort study of people treated in UK general practices. Those included in the analysis developed diabetes >40 years of age, and started treatment with oral agents or insulin after 2000. A total of 62,809 patients were divided into four groups according to whether they received monotherapy with metformin or sulfonylurea, combined therapy (metformin plus sulfonylurea), or insulin. Insulin users were grouped according to treatment with insulin glargine, long-acting human insulin, biphasic analogue and human biphasic insulin. The outcome measures were progression to any solid tumour, or cancer of the breast, colon, pancreas or prostate. Confounding factors were accounted for using Cox proportional hazards models. Results Metformin monotherapy carried the lowest risk of cancer. In comparison, the adjusted HR was 1.08 (95% CI 0.96–1.21) for metformin plus sulfonylurea, 1.36 (95% CI 1.19–1.54) for sulfonylurea monotherapy, and 1.42 (95% CI 1.27–1.60) for insulin-based regimens. Adding metformin to insulin reduced progression to cancer (HR 0.54, 95% CI 0.43–0.66). Theriskforthoseonbasalhumaninsulin alone vs insulin glargine alone was 1.24 (95% CI 0.90–1.70). Compared with metformin, insulin therapy increased the risk of colorectal (HR 1.69, 95% CI 1.23–2.33) or pancreatic cancer(HR 4.63,95% CI2.64–8.10),but did not influencethe riskofbreastorprostatecancer.Sulfonylureaswereassociated with a similar pattern of risk as insulin. Conclusions/interpretation Those on insulin or insulin secretagogues were more likely to develop solid cancers than those on metformin, and combination with metformin abolished most of this excess risk. Metformin use was associated with lower risk of cancer of the colon or pancreas, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk as compared with human insulin.

/pdf/the-influence-of-glucose-lowering-therapies-on-cancer-risk-5ftl7acgei.pdf

The influence of glucose-lowering therapies on cancer risk in type 2 diabetes

Tramadol, a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+)-Tramadol and the metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the μ. opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (−)-tramadol inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. Tramadol is available as drops, capsules and sustained-release formulations for oral use, suppositories for rectal use and solution for intramuscular, intravenous and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 hours, reach peak concentrations after 4.9 hours and have a bioavailability of 87–95% compared with capsules. Tramadol is rapidly distributed in the body; plasma protein binding is about 20%. Tramadol is mainly metabolised by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates. Tramadol and its metabolites are mainly excreted via the kidneys. The mean elimination half-life is about 6 hours. The O-demethylation of tramadol to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4. The wide variability in the pharmacokinetic properties of tramadol can partly be ascribed to CYP polymorphism. O-and N-demethylation of tramadol as well as renal elimination are stereoselective. Pharmacokinetic-pharmacodynamic characterisation of tramadol is difficult because of differences between tramadol concentrations in plasma and at the site of action, and because of pharmacodynamic interactions between the two enantiomers of tramadol and its active metabolites. The analgesic potency of tramadol is about 10% of that of morphine following parenteral administration. Tramadol provides postoperative pain relief comparable with that of pethidine, and the analgesic efficacy of tramadol can further be improved by combination with a non-opioid analgesic. Tramadol may prove particularly useful in patients with a risk of poor cardiopulmonary function, after surgery of the thorax or upper abdomen and when non-opioid analgesics are contraindicated. Tramadol is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol appears to produce less constipation and dependence than equianalgesic doses of strong opioids.

Clinical Pharmacology of Tramadol

OBJECTIVE--To determine the extent of agreement between clinical information recorded on surgery computers of selected general practitioners and similar information in manual records of letters received from hospital consultants and kept in the general practitioners9 files. DESIGN--Hospital consultants9 letters in the manual records of selected general practitioners were photocopied and the consultants9 clinical diagnoses were compared with diagnoses recorded on computer. SETTING--General practices in the United Kingdom using computers provided by VAMP Health for recording clinical information. SUBJECTS--2491 patients who received one of three non-steroidal anti-inflammatory drugs and who attended 58 practices whose computer recorded data were considered after a preliminary review to be of satisfactory quality. RESULTS--Among 1191 patients for whom consultants9 letters were forwarded a clinical diagnosis reflecting the diagnosis noted on a consultant letter was present on the computer record for 1038 (87%). CONCLUSION--Clinical information available on the computer records of the general practitioners who participated in this study is satisfactory for many clinical studies.

https://www.bmj.com/content/bmj/302/6779/766.full.pdf

Validation of information recorded on general practitioner based computerised data resource in the United Kingdom.

Study Objective. To assess the risk of idiopathic incident seizures among patients who ever took tramadol.



Design. Nested case-control design.



Setting. General Practice Research Database from November 1996–August 1998.



Patients. Eleven thousand three hundred eighty-three patients.



Intervention. Comparison of risks of idiopathic incident seizures during exposed and unexposed times among patients who had ever taken tramadol and other analgesics with 90-day follow-up.



Measurements and Main Results. Among the 11,383 subjects we identified 21 cases of idiopathic seizures, 10 of which were categorized as definite cases and 11 categorized as possible cases. Three patients were exposed to tramadol alone in the previous 90 days, 10 to opiates, three to both tramadol and opiates, one to other analgesics, and four to no analgesics.



Conclusion. The risk of idiopathic seizures was similarly elevated in each analgesic exposure category compared with nonusers, suggesting that the risk for patients taking tramadol was not increased compared with other analgesics.



(Pharmacotherapy 2000; 20(6):629–634)

Incidence of first-time idiopathic seizures in users of tramadol.

Breast cancer incidence rates in the UK from 1990 to 1996 among women aged 35-69 estimated from the General Practice Research Database (GPRD) were closely similar to those reported by the Office for National Statistics from cancer registration data (ONS). The GPRD is a valuable and up-to-date resource for further study of the incidence of breast cancer in the UK as well as changes in cancer treatment and their relation to survival trends.

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L E Derby

Papers

Validation of information recorded on general practitioner based computerised data resource in the United Kingdom.

Incidence of first-time idiopathic seizures in users of tramadol.

The incidence of breast cancer in the General Practice Research Database compared with national cancer registration data

Ovulation induction and neural tube defects.

Large computer databases.