The origin and spread of a mumps epidemic: United kingdom, 2003-2006.

BACKGROUND: The United Kingdom (UK) underwent a massive epidemic of mumps from 2003 through 2006. The origin and spread was mapped in 350 general practices that used office computers to contribute comprehensive medical information on approximately 3 million patients to the General Practice Research Database (GPRD). METHODS: The continuous 3-month cumulative incidence of mumps (2003-2006) was estimated by dividing the number of diagnosed cases of mumps each 3 months by the population at risk according to age, region, practice, and calendar time. The effect of the measles, mumps, and rubella (MMR) vaccine was estimated by comparing vaccine exposure of those diagnosed with mumps and those who were not. RESULTS: There were 5683 cases of mumps recorded in the Database over the 4-year time period. As the Database represents about 5% of the UK population, we estimate that there were more than 100,000 cases of mumps diagnosed in the UK during these 4 years. The epidemic appears to have started in one practice in Wales in the first 6 months of 2003 and then spread slowly north and east, reaching a peak in 2005. Young adults aged 18-24 years were at the highest risk. There were 3 major MMR vaccination campaigns (1988-1989, 1997, and 2004-2005) that by 2006 provided more than 70% protection against mumps in children younger than 18 years of age. Protection was higher in those who had received 2 doses of the vaccine. CONCLUSION: A comprehensive program of medical information generated by selected general practitioners has provided a sound basis for the real-time recording of the origin, spread, and scope of an infectious disease.

Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer.

OBJECTIVE: To investigate the relation of various estrogen-containing hormone therapies to the risk of breast cancer, emphasizing the use of the combination of estrogen and testosterone. METHODS: Using information from a large U.S.-based claims database, we conducted a case-control study in women aged 50 to 64 years who had a first-time diagnosis of breast cancer to estimate the effect in users of conjugated estrogen alone, conjugated estrogen plus progestin, esterified estrogen with methyltestosterone, or esterified estrogen with methyltestosterone plus progestin, compared with nonusers. Four controls were matched to each case on year of birth and index date. Odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: We identified 4,515 cases and 18,058 matched controls. The OR for users of estrogen alone compared with the nonusers was 0.96 (95% confidence interval [CI] 0.88-1.06; 667 cases and 2,900 controls); for users of conjugated estrogen plus progestin, it was 1.44 (95% CI 1.31-1.58; 712 cases and 2,087 controls); and for users of esterified estrogen with methyltestosterone and esterified estrogen with methyltestosterone plus progestin, the ORs were 1.08 (95% CI 0.86-1.36; 98 cases and 380 controls) and 1.69 (95% CI 1.03-2.79; 22 cases and 55 controls), respectively. There was an increased risk among conjugated estrogen plus progestin users of 48 months or more (OR 3.10, 95% CI 2.38- 4.04; 111 cases and 149 controls). CONCLUSION: There is no materially increased risk of breast cancer in users of estrogen alone or esterified estrogen with methyltestosterone compared with nonusers. There is an increased risk among those using conjugated estrogen plus progestin. In particular, the risk of breast cancer in women who used conjugated estrogen plus progestin for 4 or more years is approximately three times higher than in women who are not exposed to hormone therapy, so that the background incidence rate for women aged 50 to 64 years, which is around 3 per 1,000, would be increased to approximately 9 per 1,000 in women aged 50 to 64 years who have taken conjugated estrogen plus progestin for 48 months or more. LEVEL OF EVIDENCE: II.

Rate of suicide in patients taking montelukast.

STUDY OBJECTIVE: To estimate the rate of suicide in patients taking montelukast. DESIGN: Population-based cohort study. DATA SOURCE: United Kingdom General Practice Research Database. PATIENTS: A total of 23,500 patients who had received at least one prescription for montelukast in the cumulative data from February 1998-March 2007. MEASUREMENTS AND MAIN RESULTS: Rate of suicide was to be calculated as number of suicides divided by person-time at risk. Person-time of montelukast exposure was accrued for each patient as a cumulative duration of all prescriptions. The 23,500 patients had received 252,593 prescriptions for montelukast, representing 21,050 person-years at risk for suicide. We then sought to identify all cases that had a computer-recorded diagnosis of suicide; however, no cases of suicide were found in patients exposed to montelukast during our time frame. CONCLUSION: The risk of suicide attributable to montelukast, if present at all, is extremely low in users.

Proton pump inhibitor use and risk of hip fractures in patients without major risk factors.

STUDY OBJECTIVE: To estimate the relative risk of hip fracture associated with proton pump inhibitor (PPI) use in a population without major risk factors. DESIGN: A two-phase, matched, nested case-control study. DATA SOURCE: United Kingdom General Practice Research Database (GPRD). PATIENTS: Phase 1 identified 4414 case patients (aged 50-79 yrs) with an incident hip fracture between 1995 and 2005 who had at least 2 years of recorded history in the GPRD; each case was matched by age, sex, and index date (date of first-time hip fracture for cases, same date for matched controls) to up to 10 controls who did not have hip fracture. Phase 2 included the 1098 case patients identified as having no major medical risk factors for hip fracture (as assessed in phase 1) and a new set of 10,923 controls without major risk factors for hip fracture matched by sex, age, index date, and duration of history in the GPRD. MEASUREMENTS AND MAIN RESULTS: In phase 1, we identified major medical risk factors for hip fracture. In phase 2, we restricted the study to case patients with none of these risk factors and matched them to new controls, who also had none of the risk factors. Data on use of PPIs were collected and compared between the groups. The relative risk (RR) for hip fracture among patients who received any PPI prescription was 0.9 (95% confidence interval 0.7-1.1) compared with those with no PPI prescription. We found no evidence of an increased risk of hip fracture with increased PPI use. The RR estimates were similar in both sexes and in all age subgroups. No specific PPI was associated with an increased risk of hip fracture. CONCLUSION: Use of PPIs does not increase the risk of hip fracture in patients without major risk factors. The difference in results between our study and that of another, which indicated that PPI use increases the risk of hip fracture, may be due to residual confounding or effect modification in the latter study.

The contraceptive patch in relation to ischemic stroke and acute myocardial infarction.

STUDY OBJECTIVE: To compare rates of stroke and acute myocardial infarction in users of the Ortho EVRA contraceptive patch with these rates in users of norgestimate-containing oral contraceptives (OCs) with 35 microg of ethinyl estradiol. DESIGN: Retrospective, population-based, epidemiologic study. DATA SOURCE: PharMetrics database. SUBJECTS: Females aged 15-45 years in the PharMetrics database who had filled at least one prescription for the Ortho EVRA contraceptive patch or a norgestimate OC between April 1, 2002, and March 31, 2005. MEASUREMENTS AND MAIN RESULTS: Incidence rates and 95% confidence intervals (CI) were estimated for the outcomes of ischemic stroke and acute myocardial infarction by exposure. Crude incidence rates of ischemic stroke among users of the patch and users of norgestimate OCs were 13.6/100,000 woman-years (95% CI 5.9-26.8) and 11.3/100,000 woman-years (95% CI 5.4-20.8), respectively. The crude incidence rate of acute myocardial infarction was 1.7/100,000 woman-years (95% CI 0.04-9.5) in current patch users and 7.9/100,000 woman-years (95% CI 3.2-16.3) in current users of norgestimate OCs. Incidence rate ratios (IRRs) were estimated for the outcomes by comparing data for users of the patch and users of a norgestimate OC. The IRR for stroke was 1.2 (95% CI 0.41-3.4) and for acute myocardial infarction was 0.2 (95% CI 0.004-1.7). CONCLUSION: Ischemic stroke and acute myocardial infarction are rare among young women who use hormonal contraceptives, and the current data provide no suggestion of an increased risk of either ischemic stroke or acute myocardial infarction in users of the Ortho EVRA contraceptive patch compared with users of norgestimate OCs.

Statins and the risk of pneumonia: a population-based, nested case-control study.

STUDY OBJECTIVE: To determine if the use of statins affects pneumonia-related outpatient visits, hospitalizations with survival, and deaths. DESIGN: Population-based, retrospective, nested case-control analysis. DATA SOURCE: United Kingdom-based General Practice Research Database. PARTICIPANTS: The study population (134,262 patients aged > or = 30 yrs) consisted of 55,118 patients who took statins and/or fibrates, 29,144 patients with hyperlipidemia not taking lipid-lowering agents, and 50,000 randomly selected patients without hyperlipidemia and without lipid-lowering treatment. MEASUREMENTS AND MAIN RESULTS: We identified 1253 patients with pneumonia and matched them with 4838 control subjects based on age, sex, general practice, and index date. After adjusting for comorbidity and frequency of visits to general practitioners, we calculated the risks (odds ratios with 95% confidence intervals) of uncomplicated pneumonia, hospitalization for pneumonia with survival, and fatal pneumonia in participants who used statins compared with those who did not. Current statin users had a significantly reduced risk of fatal pneumonia (adjusted odds ratio 0.47, 95% confidence interval 0.25-0.88) and slightly but not significantly reduced risks of uncomplicated pneumonia and pneumonia hospitalization with survival. Recent or past statin use and fibrate use at any time were not associated with a reduced risk of pneumonia. CONCLUSION: Current use of statins was associated with a reduced risk of pneumonia. The risk reduction was particularly strong in the subgroup of patients with fatal pneumonias.

Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol.

CONTEXT: In 2006, we published a study that indicated that the new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin did not increase the risk for venous thromboembolism (VTE) compared to oral contraceptive containing norgestimate and 35 microg of EE. OBJECTIVE: This report updates information on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using oral contraceptives containing norgestimate (either monophasic or triphasic) and 35 microg of EE (norgestimate-35) using an additional 17 months of data. DESIGN, SETTING AND PARTICIPANTS: Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women, aged 15 to 44 years, who started either the contraceptive patch or norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE) who were not in the earlier study. Up to four controls were matched to each case by age and calendar time. MAIN OUTCOME MEASURES: Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives. RESULTS: We identified 56 new cases of newly diagnosed, idiopathic VTE in the updated study population. The OR comparing the contraceptive patch to norgestimate-35 was 1.1 (95% CI 0.6-2.1). CONCLUSIONS: After evaluating an additional 17 months of data, the results indicate that the risk of nonfatal VTE for the contraceptive patch is closely similar to the risk for oral contraceptives containing 35 mug of EE and norgestimate.

Nonsteroidal antiinflammatory drugs and acute myocardial infarction in patients with no major risk factors.

STUDY OBJECTIVE: To assess the risk of long-term use of five nonsteroidal antiinflammatory drugs (NSAIDs)--rofecoxib, celecoxib, ibuprofen, naproxen, and diclofenac--in relation to acute myocardial infarction. DESIGN: Five separate nested case-control studies, one for each NSAID, designed to minimize important biases present in other observational studies. Setting. University-affiliated research program. Data Source. The United Kingdom General Practice Research Database (GPRD). MEASUREMENTS AND MAIN RESULTS: We identified all people in the GPRD aged 30-79 years who had a first recorded prescription for rofecoxib, celecoxib, ibuprofen, naproxen, or diclofenac after January 1, 1999. Cases of newly diagnosed, first-time acute myocardial infarction were then identified from the study population, along with matched control subjects. Relative risk estimates for acute myocardial infarction in patients with no recorded major clinical risk factors for acute myocardial infarction were determined for each NSAID according to receipt of 2-4, 5-9, 10-19, or 20 or more prescriptions compared with receipt of only 1 prescription. Results were adjusted for relevant variables possibly related to the risk for acute myocardial infarction. No material elevation of risk according to the number of prescriptions received for ibuprofen or naproxen was noted. However, a substantial increased risk similar to that found in clinical trials was noted in patients who received 10 or more prescriptions for rofecoxib, celecoxib, or diclofenac. CONCLUSION: Extensive use of rofecoxib, celecoxib, and diclofenac increases the risk of acute myocardial infarction, but similar use of ibuprofen and naproxen does not.

Cigarette smoking and the progression of multiple sclerosis.

An increased risk of multiple sclerosis among smokers has been found in several prospective epidemiological studies. The association between smoking and progression of multiple sclerosis has not been examined. We identified patients who had a first multiple sclerosis diagnosis recorded in the General Practice Research Database (GPRD) between January 1993 and December 2000. Their diagnosis and date of first symptoms were confirmed through examination of medical records. Smoking status was obtained from the computer records. To assess the association between smoking and risk of multiple sclerosis, we conducted a case-control study nested in the GPRD. Up to 10 controls per case were randomly selected, matched on age, sex, practice, date of joining the practice and availability of smoking data. To assess the association between smoking and progression of multiple sclerosis, we conducted a cohort study of multiple sclerosis cases with a relapsing-remitting onset. Our nested case-control study included 201 cases of multiple sclerosis and 1913 controls. The odds ratio [95% confidence interval (CI)] of multiple sclerosis was 1.3 (1.0-1.7) for ever smokers compared with never smokers. Our cohort study included 179 cases with a mean (median) length of follow-up of 5.3 (5.3) years. The hazard ratio of secondary progression was 3.6 (95% CI 1.3-9.9) for ever smokers compared with never smokers. These results support the hypothesis that cigarette smoking is associated with an increased risk of multiple sclerosis, and suggest that smoking may be a risk factor for transforming a relapsing-remitting clinical course into a secondary progressive course.

Cerebral venous sinus thrombosis in users of four hormonal contraceptives: levonorgestrel-containing oral contraceptives, norgestimate-containing oral contraceptives, desogestrel-containing oral contraceptives and the contraceptive patch.

BACKGROUND: It has been suggested that the risk for cerebral venous sinus thrombosis (CVST) may be greater among users of the contraceptive patch than among users of oral contraceptives (OCs). METHODS: From the PharMetrics database, we identified women aged 15-44 years who filled at least one prescription for either the contraceptive patch or desogestrel-containing, norgestimate-containing or levonorgestrel-containing OCs to assess the risk of CVST. The person-time of current exposure to each study drug, as well as the incidence rates (IRs) and incidence rate ratios (IRRs) of CVST, was calculated. RESULTS: We identified over 1 million users of the four study drugs. There were five cases of CVST among current users of desogestrel, seven cases among current users of norgestimate, two cases among current users of levonorgestrel and none among current users of the contraceptive patch. The IRs per 100,000 woman-years were 2.7 [95% confidence interval (95% CI)=0.9-6.3], 1.6 (95% CI=0.7-3.3), 0.7 (95% CI=0.1-2.4) and 0.0 (95% CI=0.0-4.8), respectively, in users of desogestrel, norgestimate, levonorgestrel and the contraceptive patch. There were two women who had CVST while not currently taking a hormonal contraceptive (IR=0.4 per 100,000 woman-years; 95% CI=0.1-1.3). The IRRs were 4.0 (95% CI=0.7-42.4) for desogestrel-containing versus levonorgestrel-containing OCs, and 2.4 (95% CI=0.5-24.0) for norgestimate-containing versus levonorgestrel-containing OCs. The IRR for the patch could not be calculated. CONCLUSIONS: There is no evidence of an increased risk of CVST in users of the contraceptive patch compared to users of levonorgestrel-containing OCs.

Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol.

CONTEXT: There is concern that a new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin increases the risk for venous thromboembolism (VTE) compared to previously marketed oral contraceptives (OCs). OBJECTIVE: Quantitative information was obtained on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using OCs, norgestimate (either monophasic or triphasic) and 35 microg EE (norgestimate-35), an OC that has been marketed for over a decade. DESIGN, SETTING AND PARTICIPANTS: Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women aged 15 to 44, who started either the contraceptive patch or norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE). Up to four controls were matched to each case by age and calendar time. MAIN OUTCOME MEASURES: Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives and incidence rates of nonfatal VTE for new users of each of the study contraceptives. RESULTS: We identified 68 newly diagnosed, idiopathic cases of VTE in the study population. In the case-control analysis, the OR comparing the contraceptive patch to norgestimate-35 was 0.9 (95% CI 0.5-1.6). The overall incidence rate for VTE was 52.8 per 100,000 women-years (95% CI 35.8-74.9) among users of the contraceptive patch and 41.8 per 100,000 women-years among users of norgestimate-35 (95% CI 29.4-57.6), and the age-adjusted VTE incidence rate ratio (IRR) for current use of the contraceptive patch vs. norgestimate-35 was 1.1 (95% CI 0.7-1.8). CONCLUSIONS: The risk of nonfatal VTE for the contraceptive patch is similar to the risk for OCs containing 35 microg ethinylestradiol and norgestimate.

Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel.

CONTEXT: Previous studies have reported that users of the "third-generation" oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of norgestimate-containing OCs compared to other OCs, however, are lacking. OBJECTIVE: The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel. DESIGN, SETTING AND PARTICIPANTS: Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing norgestimate with 35 microg of ethinyl estradiol (EE), desogestrel with 30 microg of EE or levonorgestrel with 30 microg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs. RESULTS: Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8-1.6] and 1.7 (95% CI, 1.1-2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5-36.5), 53.5 (95% CI, 42.9-66.0) and 27.1 (95% CI, 21.1-34.3) per 100,000 woman-years for users of norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8-1.5) and 2.0 (95% CI, 1.4-2.7), respectively. CONCLUSIONS: The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.

Recent use of oral contraceptives and the risk of multiple sclerosis.

BACKGROUND: Exogenous estrogens affect the onset and clinical course of experimental allergic encephalomyelitis. Oral contraceptives, a frequent source of exogenous estrogens in humans, could have a role in the development of multiple sclerosis (MS). OBJECTIVE: To examine whether recent oral contraceptive use and pregnancy history are associated with the risk of MS. DESIGN AND SETTING: A case-control study nested in the General Practice Research Database. This database contains prospective health information (drug prescriptions and clinical diagnoses) on more than 3 million Britons who are enrolled with selected general practitioners. PARTICIPANTS: One hundred six female incident cases of MS, younger than 50 years, with at least 3 years of continuous recording in the General Practice Research Database before the date of first symptoms (index date), identified between January 1, 1993, and December 31, 2000, and 1001 controls matched on age, practice, and date of joining the practice. Main Outcome Measure Incidence of first symptoms of MS, confirmed through medical records. RESULTS: The incidence of MS was 40% lower (odds ratio, 0.6; 95% confidence interval, 0.4-1.0) in oral contraceptive users compared with nonusers during the previous 3 years. The risk of MS increased in the 6 months after pregnancy (odds ratio, 2.9, 95% confidence interval, 1.2-6.6), but it was not otherwise related to parity. CONCLUSIONS: The hormonal changes that occur during oral contraceptive use and pregnancy may be associated with a short-term reduction in the risk of MS, and the postpartum period may be associated with a short-term increase in the risk of MS.

Cesarean delivery in the United Kingdom: time trends in the general practice research database.

OBJECTIVE: To estimate recent temporal trends in delivery by cesarean during the past decade and the proportion of vaginal deliveries after prior caesarean in the United Kingdom. METHODS: We conducted a cohort study using information from the General Practice Research Database. We identified all women with 1 or more deliveries between January 1990 and December 1999 and determined the method(s) of delivery. We estimated the proportion of women with vaginal delivery after cesarean in a subcohort who had at least 3 years of follow-up. RESULTS: We identified 39,938 cesareans among 271,663 deliveries (14.7%), with an increase from 12.5% in 1990 to 18.3% in 1999. The proportion of cesarean deliveries increased with age and increased over time in all age groups except women aged younger than 20 years. Among 26,480 women with a caesarean delivery between 1990 and 1996, 7,649 (28.9%) had a subsequent delivery. The proportion of vaginal delivery after prior cesarean decreased from 45% in 1991 to 37% in 1999. CONCLUSION: Cesarean deliveries increased as a proportion of all deliveries in the United Kingdom during the past decade, and the proportion of vaginal delivery after prior cesarean decreased. Still, the proportion of cesarean deliveries is lower and the proportion of vaginal deliveries after prior cesarean is higher in the United Kingdom than in the United States. LEVEL OF EVIDENCE: II-2.

Current use of nonsteroidal antiinflammatory drugs and the risk of acute myocardial infarction.

STUDY OBJECTIVE: To evaluate the risk of acute myocardial infarction during current exposure to nonsteroidal antiinflammatory drugs (NSAIDs). DESIGN: Retrospective case-control analysis. SETTING: General practice offices. SUBJECTS: A total of 8688 case patients, aged 89 years or younger, with a first-time acute myocardial infarction and 33,923 control subjects matched on age, sex, calendar time, and general practice attended. INTERVENTION: The United Kingdom General Practice Research Database was searched for potential cases of first-time acute myocardial infarction between January 1995 and April 2001. Control subjects without acute myocardial infarction were identified at random. MEASUREMENTS AND MAIN RESULTS: Exposure to NSAIDs was assessed, and 650 case patients and 2339 control subjects were found to be currently taking NSAIDs. After adjusting for various risk factors for acute myocardial infarction (e.g., hypertension, hyperlipidemia, diabetes mellitus, ischemic heart disease, body mass index, smoking), the relative risk (expressed as odds ratio [OR]) of acute myocardial infarction was 1.07 (95% confidence interval [CI] 0.96-1.19) for subjects with current NSAID exposure compared with those not taking NSAIDs. The adjusted OR for current diclofenac use was 1.23 (95% CI 1.00-1.51), for current ibuprofen use 1.16 (95% CI 0.92-1.46), and for current naproxen use 0.96 (95% CI 0.66-1.38) compared with those not taking NSAIDs. Current aspirin use combined with current NSAID use was associated with a statistically significant risk reduction (adjusted OR 0.74, 95% CI 0.57-0.97), compared with nonuse of NSAIDs and aspirin. Current use of aspirin together with current use of ibuprofen yielded an adjusted OR of 0.69 (95% CI 0.42-1.15). CONCLUSIONS: Our results provide additional evidence that the risk of first-time acute myocardial infarction during current use of NSAIDs is not materially altered. We found no evidence for a reduced cardioprotective effect of aspirin with concomitant NSAID use.

A population-based study of the incidence, cause, and severity of anaphylaxis in the United Kingdom.

BACKGROUND: Anaphylaxis is an acute and potentially fatal systemic reaction usually caused by mast cell-mediated release of histamine. Symptoms can vary in onset, appearance, and severity. Some common symptoms include weakness, dizziness, flushing, angioedema, urticaria, nasal congestion, and sneezing. Severe symptoms include upper respiratory tract obstruction, hypotension, vascular collapse associated with angioedema and urticaria, gastrointestinal distress, cardiovascular arrhythmias, and/or arrest. METHODS: We conducted an observational follow-up study encompassing approximately 8 million person-years based on the UK General Practice Research Database for the period January 1, 1994, to December 31, 1999, which quantified the frequency, type, and severity of a clinical diagnosis of anaphylaxis. RESULTS: Based on 675 cases of anaphylaxis, we estimate the incidence to be 8.4 per 100 000 person-years. Approximately 10% of cases had hypotension and shock that required urgent treatment. The most common causes were insect stings and oral medicines. CONCLUSION: Anaphylaxis is an uncommon illness that has multiple causes and can be life-threatening.

Lipid-lowering drugs and the risk of depression and suicidal behavior.

BACKGROUND: A possible association between lipid-lowering drug therapy and psychological well-being remains an issue of debate. To provide more information, we performed a nested case-control study to evaluate the effect of lipid-lowering drugs on depression and suicidal behavior. METHODS: Within the United Kingdom General Practice Research Database, we identified all cases with newly treated depression needing a referral or hospitalization and all cases with first-recorded diagnosis of suicidal behavior between January 1, 1991, and December 31, 1999, from a study base that comprised all patients who were aged between 40 and 79 years and who had various exposures of interest. Each case was matched with up to 4 controls, randomly selected from the study base, on age, sex, medical practice, calendar time, and years since enrollment in the General Practice Research Database. RESULTS: A nested case-control analysis comprised 458 newly diagnosed cases of depression with 1830 controls, and 105 cases of suicidal behavior with 420 controls. The adjusted odds ratio of depression was 0.4 (95% confidence interval, 0.2-0.9) for current statin use, compared with hyperlipidemic nonuse. The adjusted odds ratios for other exposures were all around 1.0. None of the adjusted odds ratios for suicidal behavior were significantly different from unity. CONCLUSIONS: The use of statins and other lipid-lowering drugs is not associated with an increased risk of depression or suicide. On the contrary, individuals with current statin use may have a lower risk of developing depression, an effect that could be explained by improved quality of life due to decreased risk of cardiovascular events or more health consciousness in patients receiving long-term treatment.