Biomedical subjects

Raymond G Schlienger

Publications and source records attributed to Raymond G Schlienger.

At least 19 recordsLinked to original sources

PubMed2006

The prevalence of potential drug-drug interactions in patients with heart failure at hospital discharge.

BACKGROUND/OBJECTIVE: Pharmacotherapy for heart failure is complex and, due to polypharmacy, is associated with a large risk of potential drug-drug interactions (DDIs). The objective of the present study was to assess the prevalence of potential DDIs in the medication of hospitalised heart failure patients and to evaluate their clinical relevance. STUDY DESIGN/METHODS: The medication of 400 patients was retrospectively analysed for potential DDIs at hospital admission and discharge using a computerised drug interaction program. Main inclusion criteria were the diagnosis of heart failure and a minimum of two drug prescriptions at discharge. RESULTS: In the study population of 400 heart failure patients (median age 79 years, 55.5% men), the median number of drugs per patient was lower at admission than at discharge (6 [interquartile range {IQR} 4-9] vs 8 [IQR 6-10]; p < 0.001). At hospital admission, a total of 863 potential DDIs were detected in 272 patients (68.0%; 95% CI 63.4, 72.6). At discharge, 1171 potential DDIs were detected in 355 patients (88.8%; 95% CI 85.7, 91.8). This corresponds with a significant increase in the median number of potential DDIs per patient from admission to discharge (1.5 [IQR 0-3] vs 3 [IQR 1-4]; p < 0.001). Of the 1171 potential DDIs at discharge, 432 (36.9%) were prevalent at admission and 739 (63.1%) resulted from a medication change during the hospital stay. Of these 739 new potential DDIs, the severity of the potential adverse effect was rated as 'major' in 190 (25.7%) patients, 'moderate' in 482 (65.2%) and 'minor' in 67 (9.1%). The 190 potential DDIs with major severity were recorded in a total of 145 patients (36.3%; 95% CI 31.5, 41.0%). Hyperkalaemia was the most prevalent potential adverse effect of major severity (n = 93) and the combination of an ACE inhibitor with a potassium-sparing diuretic was recorded in 64 (16.0%) patients. CONCLUSIONS: The study shows that hospitalisation of patients with heart failure results in an increase in the number of drugs prescribed per patient and, thereby, also in the number of potentially interacting drug combinations per patient. Although electronic drug interaction programs are a valuable tool to check for potential DDIs, the clinical relevance of most potential DDIs can only be judged by assessment of the individual patient.

Aged↗

PubMed2006

Prevalence of potentially inappropriate medication use in elderly patients: comparison between general medical and geriatric wards.

BACKGROUND AND OBJECTIVE: Inappropriate drug use is one of the risk factors for adverse drug reactions in the elderly. We hypothesised that, in elderly patients, geriatricians are more aware of potentially inappropriate medications (PIMs) and may replace or stop PIMs more frequently compared with internists. We therefore evaluated and compared the prevalence of PIMs as well as anticholinergic drug use throughout hospital stay in elderly patients admitted to a medical or geriatric ward. METHODS: In this retrospective cross-sectional study, 800 patients aged > or =65 years admitted to a general medical or geriatric ward of a 700-bed teaching hospital in Switzerland during 2004 were included. PIMs were identified using the Beers criteria published in 2003. The prevalence of anticholinergic drug use was assessed based on drug lists published in the literature. RESULTS: The prevalence of use of PIMs that should generally be avoided was similar in medical and geriatric inpatients both at admission (16.0% vs 20.8%, respectively; p = 0.08) and at discharge (13.3% vs 15.9%, respectively; p = 0.31). In contrast to medical patients, the reduction in the prevalence of use of PIMs between admission and discharge in geriatric patients reached statistical significance (p < 0.05). Overall, the three most prevalent inappropriate drugs/drug classes were amiodarone, long-acting benzodiazepines and anticholinergic antispasmodics. At admission, the prevalence of use of PIMs related to a specific diagnosis was not significantly different between patients hospitalised to a medical or a geriatric ward (14.0% vs 17.5%, respectively; p = 0.17), as compared with the significant difference evident at hospital discharge (11.7% vs 23.7%, respectively; p < 0.001). This was largely because of a higher prescription rate of platelet aggregation inhibitors in combination with low-molecular-weight heparins and benzodiazepines in patients with a history of falls and syncope. The proportions of patients taking anticholinergic drugs in medical and geriatric patients at admission (13.0% vs 17.5%, respectively; p = 0.08) and discharge (12.2% vs 16.5%, respectively; p = 0.10) were similar. CONCLUSION: Inappropriate drug use as defined by the Beers criteria was common in both medical and geriatric inpatients. Compared with internists, geriatricians appear to be more aware of PIMs that should generally be avoided, but less aware of PIMs related to a specific diagnosis, and of the need to avoid anticholinergic drug use. However, the results of this study should be interpreted with caution because some of the drugs identified as potentially inappropriate may in fact be beneficial when the patient's clinical condition is taken into consideration.

Aged↗

PubMed2005

Hepatotoxicity during rapid intravenous loading with amiodarone: Description of three cases and review of the literature.

OBJECTIVE: Atrial fibrillation is the most common arrhythmia after cardiac surgery. Amiodarone can effectively prevent and control postoperative atrial and ventricular fibrillation. Acute hepatic damage after intravenous amiodarone, which can be fatal, is not well recognized. We describe three cases of acute hepatocellular injury after intravenous amiodarone administration in critically ill patients. Another 25 published cases and six cases reported to the Swiss Pharmacovigilance Center (Swissmedic) are discussed. DESIGN: This study consisted of a series of three case reports and review of the literature. SETTING: : This study was conducted at an operative critical care unit at the University Hospital Basel, Switzerland. PATIENTS: Three hemodynamically compromised patients after open heart surgery developed significant increases of transaminases (up to more than 100-fold of the upper limit of normal) shortly after the introduction of intravenous amiodarone. INTERVENTIONS AND MEASUREMENT: Cessation of intravenous amiodarone and of other potentially hepatotoxic drugs. RESULTS: Liver parameters significantly improved or returned to normal in all three patients, even after start of oral amiodarone in two patients. CONCLUSIONS: Amiodarone is a highly effective antiarrhythmic agent for the treatment and prevention of atrial and ventricular arrhythmias. Acute liver damage after intravenous amiodarone, possibly induced by the solubilizer polysorbate 80, is rare but potentially harmful. Amiodarone loading should therefore be adapted to the necessity of an immediate effect of the drug, and liver function should be monitored closely in critically ill patients. Oral maintenance therapy with amiodarone is possible, even in patients who developed liver disease during intravenous loading.

Aged↗

PubMed2005

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.

Adult↗

PubMed2005

Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy.

BACKGROUND: Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia. METHODS: Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program. RESULTS: We included 2742 ambulatory statin-treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/- SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients. CONCLUSIONS: CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.

Aged↗

PubMed2005

Corticosteroid-associated tendinopathies: an analysis of the published literature and spontaneous pharmacovigilance data.

INTRODUCTION AND OBJECTIVE: Corticosteroids may cause tendinopathies, an adverse effect that is not well known and characterised, although it was initially described more than 40 years ago. This study was conducted in order to characterise the important aspects of this adverse reaction, such as the role played by routes of corticosteroid administration, therapy duration, comedication, cumulative corticosteroid dose and underlying disease. STUDY DESIGN AND METHODS: Published case reports of tendinopathies that were associated with corticosteroid use were identified by a comprehensive literature search using the databases MEDLINE, Pharm-line, EMBASE, ToxFile, Adis Inpharma, International Pharmaceutical Abstracts, Drug Information Fulltext and PASCAL. The reference lists of all pertinent articles were cross-referenced to retrieve additional cases. Spontaneous reports were requested from the Uppsala Monitoring Centre (the WHO Collaborating Centre for International Drug Monitoring). Information of published and spontaneous reports was analysed with regard to age, sex, underlying disease, individual corticosteroids, equivalent corticosteroid dose, latency time, cumulative dose, route of administration, comedication and type of tendinopathy. RESULTS: We included and analysed 73 published case reports and case series involving 133 patients and 191 spontaneous reports of corticosteroid-associated tendinopathies. The proportion of women with tendinopathies was 50.8% and 41.0%, respectively. The mean age (+/- standard deviation) of patients with a tendinopathy was 50 +/- 17 years and 61 +/- 16 years, respectively. The predominant routes of administration were oral (33% of published cases and 47% of spontaneous cases) and intra-articular (35% of the published cases or parenteral (7% of the spontaneous cases). There were isolated cases of tendinopathy after inhaled or topical (i.e. ocular, cutaneous, nasal) corticosteroid use. Tendinopathies that were reported in the literature cases consisted mainly of tendon ruptures (93%), predominantly of the Achilles tendon. Of the spontaneous cases, 31% had a rupture and the remaining cases had a tendinitis or an unspecified tendon disorder. CONCLUSION: Oral and parenteral applications, especially intra-articular use, were the most prevalent routes of administration in cases with corticosteroid-associated tendinopathies. However, topical application has also been rarely associated with tendinopathies. Future pharmacoepidemiological studies should further address this issue to quantify the risk of corticosteroid-associated tendinopathies.

Adolescent↗

PubMed2005

[Dealing with adverse drug reactions in dentistry. Procedures on encountering adverse drug reactions and goal of the Swiss Pharmacovigilance system].

Dentists may be confronted with adverse drug reactions (ADRs) in their dental practice, and are--like other health professionals--obliged to report certain ADRs. The aim of this article is to sensitise dentists for this topic, to show how to proceed in case of a supposed ADR, and to emphasise the importance of spontaneous reporting of ADRs. ADRs may not always be clearly distinguished from symptoms of underlying diseases, and in cases of polypharmacy multiple drugs may be responsible for the reaction. It is therefore important to get a detailed medical history, and to establish a temporal relationship between start of a therapy and appearance of the symptom. Information from the medical literature, exclusion of other possible causes, and identification of risk factors help to confirm a causal relationship between a suspected drug and an observed reaction. In Switzerland severe and unexpected ADRs have to be reported to one of the regional Pharmacovigilance centres with the yellow ADR reporting form from Swissmedic. The spontaneous reports of ADRs help to early identify new problems of a drug therapy, and permit to take measures to minimise the risk.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Use of beta-blockers and risk of fractures.

CONTEXT: Animal studies suggest that the beta-blocker propranolol increases bone formation, but data on whether use of beta-blockers (with or without concomitant use of thiazide diuretics) is associated with reduced fracture risk in humans are limited. OBJECTIVE: To determine whether use of beta-blockers alone or in combination with thiazides is associated with a decreased risk of fracture in adults. DESIGN, SETTING, AND PARTICIPANTS: Case-control analysis using the UK General Practice Research Database (GPRD). The study included 30,601 case patients aged 30 to 79 years with an incident fracture diagnosis between 1993 and 1999 and 120,819 controls, matched to cases on age, sex, calendar time, and general practice attended. MAIN OUTCOME MEASURES: Odds ratios (ORs) of having a fracture in association with use of beta-blockers or a combination of beta-blockers with thiazides. RESULTS: The most frequent fractures were of the hand/lower arm (n = 12,837 [42.0%]) and of the foot (n = 4627 [15.1%]). Compared with patients who did not use either beta-blockers or thiazide diuretics, the OR for current use of beta-blockers only (> or =3 prescriptions) was 0.77 (95% confidence interval [CI], 0.72-0.83); for current use of thiazides only (> or =3 prescriptions), 0.80 (95% CI, 0.74-0.86); and for combined current use of beta-blockers and thiazides, 0.71 (95% CI, 0.64-0.79). Data were adjusted for smoking; body mass index; number of practice visits; and use of calcium channel blockers, angiotensin-converting enzyme inhibitors, antipsychotics, antidepressants, statins, antiepileptics, benzodiazepines, corticosteroids, and estrogens. CONCLUSIONS: Our data suggest that current use of beta-blockers is associated with a reduced risk of fractures, taken alone as well as in combination with thiazide diuretics. Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with beta-blockers and thiazides.

Adrenergic beta-Antagonists↗

PubMed2004

Rhabdomyolysis in association with simvastatin and amiodarone.

OBJECTIVE: To report a case of severe myopathy associated with concomitant simvastatin and amiodarone therapy. CASE SUMMARY: A 63-year-old white man with underlying insulin-dependent diabetes, recent coronary artery bypass surgery, and postoperative hemiplegia was treated with aspirin, metoprolol, furosemide, nitroglycerin, and simvastatin. Due to recurrent atrial fibrillation, oral anticoagulation with phenprocoumon and antiarrhythmic treatment with amiodarone were initiated. Four weeks after starting simvastatin 40 mg/day and 2 weeks after initiating amiodarone 1 g/day for 10 days, then 200 mg/day, he developed diffuse muscle pain with generalized muscular weakness. Laboratory investigations revealed a significant increase of creatine kinase (CK) peaking at 40 392 U/L. Due to a suspected drug interaction of simvastatin with amiodarone, both drugs were stopped. CK normalized over the following 8 days, and the patient made an uneventful recovery. An objective causality assessment revealed that the myopathy was probably related to simvastatin. DISCUSSION: Myopathy is a rare but potentially severe adverse reaction associated with statins. Besides high statin doses, concomitant use of fibrates, defined comorbidities, and concurrent use of inhibitors of cytochrome P450 are important additional risk factors. This is especially relevant if statins predominantly metabolized by CYP3A4 are combined with inhibitors of this isoenzyme. Amiodarone is a potent inhibitor of several different CYP isoenzymes, including CYP3A4. CONCLUSIONS: Avoiding the concomitant use of drugs with the potential to inhibit CYP-dependent metabolism (eg, amiodarone) or elimination of statins may decrease the risk of statin-associated myopathy. Alternatively, if drug therapy with a potent CYP inhibitor is inevitable, choosing a statin without relevant CYP metabolism (eg, pravastatin) should be considered.

Amiodarone↗

PubMed2004

Effect of rheumatoid arthritis or systemic lupus erythematosus on the risk of first-time acute myocardial infarction.

We explored the association between diagnosed rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and the risk of developing a first-time acute myocardial infarction (AMI) by conducting a population-based, case-control analysis using data from the United Kingdom-based General Practice Research Database (GPRD). Among 8,688 patients with AMI and 33,329 matched controls, the adjusted odds ratio (ORs) of AMI for subjects with RA was 1.47 (95% confidence interval [CI] 1.23 to 1.76), and in subjects with both RA and diagnosed hyperlipidemia, the OR was 7.12 (95% CI 4.16 to 12.18). The risk associated with SLE was 2.67 (95% CI 1.34 to 5.34). These results underline that RA and SLE increase the risk of AMI.

Aged↗

PubMed2004

Inhaled corticosteroids and the risk of fractures in children and adolescents.

OBJECTIVE: To determine whether children or adolescents who are exposed to inhaled corticosteroids (ie, beclomethasone, budesonide, fluticasone) are at a higher risk of having bone fractures compared with nonexposed individuals. METHODS: We performed a population-based nested case-control analysis using data from the United Kingdom-based General Practice Research Database. Within a base population of 273,456 individuals aged 5 to 79 years, we identified by International Classification of Diseases codes children or adolescents who were aged 5 to 17 years with a fracture diagnosis and up to 6 control subjects per case matched to cases on age, gender, general practice attended, calendar time, and years of history in the GPRD. We compared use of inhaled steroids before the index date between fracture cases and control patients. RESULTS: We identified 3744 cases and 21,757 matched control subjects aged 5 to 17 years. Current exposure to inhaled steroids did not reveal a substantially altered fracture risk compared with nonusers, even in individuals with current longer term exposure (ie, > or =20 prescriptions; adjusted odds ratio 1.15; 95% confidence interval: 0.89-1.48). In individuals with current or previous exposure to oral steroids, the adjusted odds ratio for current long-term inhaled steroid use compared with nonusers was 1.21 (95% confidence interval: 0.99-1.49). CONCLUSIONS: Exposure to inhaled steroids does not materially increase the fracture risk in children or adolescents compared with nonexposed individuals.

Administration, Inhalation↗

PubMed2004

Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.

BACKGROUND: It has been suggested that increased platelet activation increases the risk of acute myocardial infarction (AMI) in patients with depression. Selective serotonin reuptake inhibitors (SSRIs) may attenuate platelet activation by serotonin depletion in platelets. Observational studies have shown discrepant results of AMI risk associated with the use of SSRIs. OBJECTIVE: The aim of this study was to evaluate the association of exposure to different groups of antidepressants, including SSRIs, and the risk of AMI. The study also assessed in more detail the influence of timing of the exposure to antidepressants in a general adult population (<90 years of age), with or without diagnosed risk factors for AMI. STUDY DESIGN/METHODS: We conducted a population-based case-control analysis on the UK General Practice Research Database (GPRD). The study included 8688 patients (<90 years of age), with a first-time AMI between 1995 and 2001, and 33 923 controls, who were matched by age, sex, calendar time, and general practice. Conditional logistic regression was used to estimate odds ratios (ORs). RESULTS: Current use of an antidepressant was defined as a supply of the last prescription for an antidepressant that lasted up to the index date or beyond. Recent past use was defined as a supply of the last prescription for an antidepressant that ended 1-29 days before the index date. SSRIs investigated were citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine. Non-SSRIs investigated were amitriptyline, clomipramine, dosulepin, doxepin, imipramine, lofepramine, nefazodone, trazodone and trimipramine. Other antidepressants included were amoxapine, desipramine, lithium, maprotiline, mianserin, moclobemide, nortriptyline and protriptyline. Adjusted ORs (with 95% CI) for the current use of SSRIs, non-SSRIs, or other antidepressants, compared with non-use of antidepressants, were 0.63 (95% CI 0.43, 0.91; p=0.02), 0.92 (95% CI 0.77, 1.09; p=0.32) and 0.59 (95% CI 0.29, 1.20; p=0.14), respectively. The adjusted OR of recent past use of SSRIs compared with non-use of SSRIs was 1.42 (95% CI 1.02, 1.97; p=0.04). CONCLUSION: The present analysis provides further evidence that the current use of SSRIs is associated with a slightly decreased risk for AMI.

Age Distribution↗

PubMed2003

Appropriateness of serum level determinations of antiepileptic drugs.

AIM: To assess the appropriateness of the determination of the serum levels of the antiepileptic drugs (AEDs) phenytoin, valproic acid and carbamazepine in inpatients of a tertiary care institution. METHODS: We performed a retrospective analysis of 602 AED serum level determinations. Appropriateness criteria regarding indication and timing were defined a priori using existing criteria from the literature. The main outcome measure was the proportion of serum levels with an appropriate indication and sampling time. RESULTS: Of 602 levels assessed, 463 (77%; 95% confidence interval [95% CI], 74-80%) had an appropriate indication with a range of 68% to 84% for individual AEDs; overall, 65% (95% CI: 61-69%) met the criteria for appropriate timing. Combining the two criteria, 268 (48%; 95% CI: 44-52%) AED level measurements were assessed as appropriate. Of 139 (23%, 95% CI: 20-27%) levels assessed as having an inappropriate indication, the majority (77%) were performed for routine monitoring. CONCLUSIONS: Less than half of all AED measurements met our criteria for appropriate AED level determinations. This creates unnecessary costs. Our data indicate the need for means to improve the rational use of AED serum level determination.

Adolescent↗

PubMed2003

Potential drug-drug interactions in the medication of medical patients at hospital discharge.

OBJECTIVE: Information on the frequency of drug combinations with the potential to induce dangerous drug-drug interactions (DDIs) in patients discharged from the hospital is scarce. With the present study, we assessed the frequency and potential clinical significance of DDIs in the prescriptions of discharged medical patients. METHODS: We retrospectively screened the medication for potential DDIs of 500 patients consecutively discharged with at least two prescriptions using a computerised drug-interaction program. RESULTS: The 500 patients (56.6% male, mean age 67.0+/-15.9 years, median length of stay 13 days) were prescribed a median of six drugs (range 2-18) at discharge. Three hundred patients (60.0%; 95% confidence interval 55.7-64.3%) had at least one potentially interacting drug combination. Of 747 potential DDIs at discharge overall, 402 (53.8%) were new at the time of discharge due to a change of the medication during the hospital stay. Of these, 72 (17.9%) were of potentially minor, 281 (69.9%) of moderate and 49 (12.2%) of major severity. Of 44 patients with a potential DDI with major severity, 1 patient was re-hospitalised within 2 months after discharge due to a probable drug-related problem associated with the potential DDI. CONCLUSIONS: Using a computerised drug-interaction program, a high proportion of patients was detected with at least one potential DDI in the medication prescribed at discharge. However, the proportion of DDIs associated with potentially relevant clinical consequences appeared to be relatively low.

Aged↗

PubMed2003

Drug-induced erythroderma with high fever--is it drug hypersensitivity syndrome?

Explore the source record for details and available documents.

Butanones↗

PubMed2003

Validity of the general practice research database.

The United Kingdom General Practice Research Database (GPRD) is an office-based, computer-generated, medical resource designed from its inception to be used for epidemiologic research. A distinct version of the GPRD is maintained by the Boston Collaborative Drug Surveillance Program and has been the source of more than 130 scientific articles primarily addressing drug safety issues. We reviewed evidence related to the validity of the GPRD. Specifically, with our extensive experience with this automated database, we evaluated the quality and completeness of the data that it contains.

Databases, Factual↗

PubMed2003

HMG-CoA reductase inhibitors in osteoporosis: do they reduce the risk of fracture?

Osteoporosis affects a large number of people in industrialised countries. It has clinical and public-health impacts, most importantly due to subsequent fractures. Osteoporotic fractures are one of the most common causes of disability and are associated with enormous healthcare expenditure. The majority of existing treatment options for osteoporosis only inhibit bone resorption and prevent excessive bone loss but are not capable of stimulating bone formation. However, several recent in vitro and in vivo studies in animals demonstrated that HMG-CoA reductase inhibitors stimulate the production of bone morphogenetic protein (BMP-2), which is a potent regulating protein in osteoblast differentiation and activity. This suggests that HMG-CoA reductase inhibitors may have an anabolic effect on bones, making them a potentially interesting treatment option for osteoporosis. Additionally, several studies in humans showed that some HMG-CoA reductase inhibitors may have a beneficial effect on bone turnover and may lead to an increase in bone mineral density. Consequently, several observational studies tried to evaluate whether use of HMG-CoA reductase inhibitors is associated with a decreased risk of fractures. Even though not all results of these epidemiological studies, using different designs in different study populations, were entirely consistent, they provided substantial evidence that HMG-CoA reductase inhibitor use may decrease the bone fracture risk by approximately 50%. On the other hand, reanalysis of two randomised controlled trials of HMG-CoA reductase inhibitor therapy, designed to assess cardiovascular outcomes, could not show that patients treated with HMG-CoA reductase inhibitors had a lower fracture risk in comparison with placebo-treated patients. Therefore, to conclusively assess the potential of HMG-CoA reductase inhibitors in the prevention and treatment of osteoporosis, randomised controlled trials need to be performed to address this conflicting issue. Until the results of such trials are available, practitioners should prescribe the drugs that have been proven to reduce the risk of osteoporotic fractures.

Animals↗

PubMed2003

Effect of selective serotonin reuptake inhibitors on platelet activation: can they prevent acute myocardial infarction?

In recent years a large body of evidence from several longitudinal studies has emerged suggesting that depression is an independent risk factor for cardiovascular disease (CVD) and that the association between depression and increased CVD risk is not merely due to negative mood-driven behavior related with depression. Even though the underlying mechanisms are not well understood, several hypotheses and explanations have been proposed such as increased activation of the hypothalamic-pituitary-adrenal axis, abnormalities in the sympathoadrenal system, or abnormalities in platelet function. Platelet function abnormalities, including increased platelet reactivity, may predispose patients with depressive disorders to clotting diatheses and may explain their vulnerability to CVD. Serotonin secreted by platelets induces both platelet aggregation and coronary vasoconstriction. Even though serotonin itself is only a weak platelet agonist, it markedly enhances platelet reactions to a variety of other agonists. Several studies have shown that selective serotonin reuptake inhibitors (SSRIs) reduce platelet and whole blood serotonin concentrations after repeated doses, and could therefore exert an inhibitory effect on platelet activation. For that reason, it was hypothesized that SSRIs could have a protective effect against myocardial infarction (MI). Results from three currently available epidemiological studies assessing the risk of MI in patients treated with antidepressants, including SSRIs, are controversial with respect to a potential beneficial effect of SSRIs on CVD risk in depressed patients. However, there is evidence that exposure to SSRIs does not substantially increase the risk of CVD in patients. A recent randomized, double-blind, placebo-controlled, multicenter trial that evaluated the safety and efficacy of the SSRI sertraline in patients with major depression and acute MI or unstable angina suggested that sertraline is well tolerated and effective. Further epidemiological studies or longer-term clinical trials may shed more light on this issue, and answer the question conclusively, whether the effect of SSRIs on platelets or another mechanism translates into a decreased risk of CVD in depressed patients.

Cardiovascular Diseases↗