Nonsteroidal Anti-inflammatory Drugs Risk Research Articles

The Effect of High-Dose Corticosteroids on Cervical Spinal Fusion: A Report of Two Cases.

1Institute for Modern & Innovative Surgery, 1100 West Oakland Park Boulevard, Suite 3, Fort Lauderdale, FL 33311. E-mail address for K.R. Chin: [email protected] 2Less Exposure Surgery (LES) Society, 300 East Oakland Park Boulevard, Suite 502, Fort Lauderdale, FL 33334

IκBKβ and NFκB1 , NSAID use and risk of colorectal cancer in the Colon Cancer Family Registry

The NFκB-signaling pathway regulates cell proliferation and inflammation. Activation of the pathway is implicated in the etiology of colorectal cancer (CRC). NSAIDs may reduce CRC risk partially through a nuclear factor-kappa B (NFκB)-dependent pathway. In this study, we investigated associations between 34 NFκB1 and 8 IκBKβ tagSNPs and CRC risk and examined interactions with non-steroidal anti-inflammatory drug (NSAID) use. Using conditional logistic regression, we investigated these associations among 1584 incident CRC cases and 2516 sibling controls from the Colon Cancer Family Registry. Three IκBKβ SNPs were associated with a statistically significant lower colorectal or colon cancer risk: rs9694958 (A>G intron 5) (colorectal: OR(hzv) = 0.26(0.07-0.99), P(trend) = 0.048, P(adj) = 0.25), rs10958713 (A>C intron 19) (colon: OR(hzv) = 0.62(0.42-0.92), P(trend) = 0.005, P(adj) = 0.03) and rs5029748 (C>A intron 2) (colon: OR(het) = 0.72(0.56-0.91), P(trend) = 0.01, P(adj) = 0.08). We replicated trends associated with NFκB1 and IκBKβ variants identified in a previous study (rs4648110 (T>A intron 22), rs13117745 (G>A intron 5) and rs3747811 (T>A intron 1)). IκBKβ's rs6474387 (C>T intron 20) and rs11986055 (A>C intron 2) showed substantially lower colon cancer risk among current NSAID users (P(interaction) = 0.01 and P(interaction) = 0.045, respectively), whereas NFκB1's rs230490 (G>A 5' (outside UTR)) and rs997476 (C>A 3' (outside UTR)) showed higher CRC risk among current NSAID users (P(interaction) = 0.01 and P(interaction) = 0.03, respectively). These findings suggest that variants in NFκB1 and IκBKβ are associated with CRC risk and NSAIDs may function partially through an NFκB-dependent pathway. The SNPs identified here should be considered for future functional studies and may be useful in designing a pharmacogenetic approach to preventive NSAID use.

Long-term NSAID use and incident urothelial cell carcinoma in the VITamins and Lifestyle (VITAL) study

PurposeLiterature on the chemopreventive role of nonsteroidal anti-inflammatory drugs (NSAIDs) in urothelial carcinoma of the bladder (UC) is conflicting. A recent pooled analysis of 3 cohorts reported regular use of nonaspirin NSAIDs was associated with reduced risk of urothelial carcinoma (UC) among nonsmokers only; however, nonsmokers are a group with a low risk of UC. We examine the association between NSAID use and UC risk. Materials and methodsStudy participants were members of the VITamins and Lifestyle (VITAL) cohort of 77,048 Washington State residents aged 50–76 years who completed a baseline questionnaire in 2000–2002 on NSAID use and cancer risk factors. Ten-year use of aspirin and other NSAIDs was categorized as none, low-use (1–3 d/wk or <4 years), or high-use (≥4 d/wk and ≥4 years). Incident UC cases were prospectively identified via linkage to a local cancer registry. Hazard ratios (HR) were estimated by multivariate Cox regression. ResultsA total of 385 incident cases of UC were diagnosed over a mean follow-up of 7 years. There was no association with NSAID use and risk of UC. However, the association of use of nonaspirin NSAIDs with UC risk differed by smoking status (P for interaction = 0.02). Specifically, among long-term former smokers (quit ≥10 years), nonaspirin NSAID use was associated with a 31% reduction in risk of UC in low-users (HR 0.69, 95% CI 0.46–1.04), and 48% reduction in risk for high-users (HR 0.52, 95% CI 0.24–1.11, P for trend = 0.02). ConclusionsOur results show a risk reduction with nonaspirin NSAID use among long-term quitters, a group with significant risk of UC.

Dispensed Selective and Nonselective Nonsteroidal Anti-inflammatory Drugs and the Risk of Moderate to Severe Hyperkalemia: A Nested Case-Control Study

It is not known whether nonselective and cyclooxygenase 2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) differ in terms of hyperkalemia risk. The aim of this study was to compare the differential risk of hyperkalemia associated with various NSAIDs. Nested case-control study. New NSAID users receiving care in the US Department of Veterans Affairs (VA) health care system from October 2000 to September 2006. PREDICTOR OF FACTOR: Different NSAIDs ordered by COX-2 selectivity. Risk of hyperkalemia (defined as first serum potassium value ≥6.0 mEq/L) was estimated with a multivariate conditional logistic model adjusting for age, race, morbidities, medications, and contrast media. We identified 18,326 cases of hyperkalemia and 355,106 matched controls. Risk of hyperkalemia did not differ in patients using a single NSAID (adjusted OR, 1.03; 95% CI, 0.98-1.08) or 2 or more NSAIDs (OR, 1.16; 95% CI, 0.96-1.41) compared with patients no longer using an NSAID. However, risk varied by specific NSAID and elevated risks were found for use of rofecoxib, celecoxib, diclofenac, and indomethacin, but not meloxicam, etodolac, piroxicam, sulindac, ibuprofen, naproxen, and ketorolac. Interactions were found between NSAID use and exposure to renin-angiotensin blockers and contrast media. Some NSAIDs are available over the counter and women are under-represented in the VA population. NSAIDs may not by themselves carry a higher risk of moderate to severe hyperkalemia. Certain NSAIDs may increase the risk of hyperkalemia, but it is not related to COX-2 selectivity of the NSAID and may depend on concurrent exposure to other agents.

Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in full-term pregnant women leads to fetal or neonatal toxicity, such as constriction of the ductus arteriosus (DA) and persistent pulmonary hypertension in the newborn. The aim of this study was to predict quantitatively the fetal toxicity of three NSAIDs (antipyrine, salicylic acid and diclofenac) using the transplacental pharmacokinetic parameters obtained from our previous placental perfusion studies. Human fetal plasma concentration profile after oral administration of each NSAID to the mother was estimated using the transplacental pharmacokinetic parameters and pharmacokinetic parameters in adult women. The fetal plasma concentration-response relationship for the three NSAIDs was estimated by pharmacokinetic/pharmacodynamic analysis of the results of previous studies investigating the effects of NSAIDs on the ratio of inner diameter of the DA to that of the pulmonary artery (DA/PA) in rats and the plasma concentration profiles of NSAIDs in pregnant rats. The risk of constriction of the DA was well predicted by the model. Mean DA/PA ratio after oral administration of diclofenac to the mother was estimated to be 39.0%, whereas both of the corresponding values after oral administration of antipyrine and salicylic acid were estimated to be 5.9%. These results suggest that the fetal risk of diclofenac is higher than those of salicylic acid and antipyrine. This study presents a novel approach to predict quantitatively the fetal risk of NSAIDs administered to the mother. Human placental perfusion study and pharmacokinetic/pharmacodynamic analysis may provide basic data for predicting human fetal toxicity of drugs.

NSAIDs Protect Against Skin Cancer

Experimental models have shown procarcinogenic effects of cyclooxygenase (COX) enzymes, which promote inflammation, facilitate invasion through the basement membrane zone, suppress host antitumor defense mechanisms, inhibit tumor cell apoptosis, and stimulate angiogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) block COX activity. These authors examined the association between NSAID use and risk for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) in patients with histologically …

Nonsteroidal Anti-inflammatory Drugs and Glioma in the NIH-AARP Diet and Health Study Cohort

Several case-control studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce risk for glioblastoma, an aggressive form of brain cancer. Prospective investigations have not observed such an association, but these studies lacked adequate brain cancer case numbers and did not stratify by histologic subtype. We prospectively investigated the association between NSAID use and risk of all glioma as well as the risk of glioblastoma subtype in the National Institutes of Health (NIH)-AARP Diet and Health Study. The frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using a self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox regression models with age as the underlying time metric, adjusted for sex, race, and history of heart disease. The analysis included 302,767 individuals, with 341 incident glioma cases (264 glioblastoma). No association was observed between regular use (>2 times/wk) of aspirin and risk of glioma (HR = 1.16; 95% CI, 0.87-1.56) or glioblastoma (HR = 1.17; 95% CI, 0.83-1.64) as compared with no use. Null associations were also observed for nonaspirin NSAID use (HR for glioma = 0.90; 95% CI, 0.65-1.25 and HR for glioblastoma = 0.83; 95% CI, 0.56-1.20) as compared with no use. Our findings from this large prospective study do not support an inverse association between NSAIDs and risk of all glioma or glioblastoma.

Aspirin, Nonsteroidal Anti-inflammatory Drugs, Acetaminophen, and Pancreatic Cancer Risk: a Clinic-Based Case–Control Study

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAID) show indisputable promise as cancer chemoprevention agents. However, studies have been inconsistent as to whether aspirin has a protective effect in development of pancreatic cancer. To further evaluate the association between aspirin, NSAID, and acetaminophen use with pancreatic cancer risk, we used a clinic-based case-control study of 904 rapidly ascertained histologically or clinically documented pancreatic ductal adenocarcinoma cases, and 1,224 age- and sex-matched healthy controls evaluated at Mayo Clinic from April 2004 to September 2010. Overall, there is no relationship between non-aspirin NSAID or acetaminophen use and risk of pancreatic cancer. Aspirin use for 1 d/mo or greater was associated with a significantly decreased risk of pancreatic cancer (OR = 0.74, 95% CI: 0.60-0.91, P = 0.005) compared with never or less than 1 d/mo. Analysis by frequency and frequency-dosage of use categories showed reduced risk (P = 0.007 and 0.022, respectively). This inverse association was also found for those who took low-dose aspirin for heart disease prevention (OR = 0.67, 95% CI: 0.49-0.92, P = 0.013). In subgroup analyses, the association between aspirin use and pancreatic cancer was not significantly affected by pancreatic cancer stage, smoking status, or body mass index. Our data suggest that aspirin use, but not non-aspirin NSAID use, is associated with lowered risk of developing pancreatic cancer.

Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO)

To investigate the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) lower lung cancer risk. We analysed pooled individual-level data from seven case-control and one cohort study in the International Lung Cancer Consortium (ILCCO). Relative risks for lung cancer associated with self-reported history of aspirin and other NSAID use were estimated within individual studies using logistic regression or proportional hazards models, adjusted for packyears of smoking, age, calendar period, ethnicity and education and were combined using random effects meta-analysis. A total of 4,309 lung cancer cases (mean age at diagnosis 65years, 45% adenocarcinoma and 22% squamous-cell carcinoma) and 58,301 non-cases/controls were included. Amongst controls, 34% had used NSAIDs in the past (81% of them used aspirin). After adjustment for negative confounding by smoking, ever-NSAID use (affirmative answer to the study-specific question on NSAID use) was associated with a 26% reduction (95% confidence interval 8 to 41%) in lung cancer risk in men, but not in women (3% increase (-11% to 30%)). In men, the association was stronger in current and former smokers, and for squamous-cell carcinoma than for adenocarcinomas, but there was no trend with duration of use. No differences were found in the effects on lung cancer risk of aspirin and non-aspirin NSAIDs. Evidence from ILCCO suggests that NSAID use in men confers a modest protection for lung cancer, especially amongst ever-smokers. Additional investigation is needed regarding the possible effects of age, duration, dose and type of NSAID and whether effect modification by smoking status or sex exists.

The use of nonsteroidal anti-inflammatory drugs and the risk of Barrett’s oesophagus

Epidemiological studies have consistently reported inverse associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and oesophageal adenocarcinoma, but few have investigated associations with the precursor lesion, Barrett's oesophagus. To investigate the relationship between NSAID use and risk of Barrett's oesophagus. We conducted a large population-based case-control study that collected information on patterns of intake for aspirin and non-aspirin NSAIDs during the past 5 years and other exposures from 285 patients with nondysplastic Barrett's oesophagus, 108 patients with dysplastic Barrett's oesophagus, and two separate control groups: 313 endoscopy patients with acute inflammatory changes ('inflammation controls') and 644 population controls. We calculated odds ratios (ORs) and 95% CIs using unconditional logistic regression. Use of aspirin was not associated with nondysplastic Barrett's oesophagus when compared with population (OR=1.01, 95% CI 0.71-1.43) or inflammation controls (OR=1.16, 95% CI 0.80-1.68). Whereas we observed significant risk reductions for use of non-aspirin NSAIDs when nondysplastic Barrett's oesophagus cases were compared with population controls (OR=0.69, 95% CI 0.49-0.97), the effect was weaker and nonsignificant when cases were compared with inflammation controls (OR=0.82, 95% CI 0.57-1.18), and no dose-response effects were present in either analysis. We found no evidence that aspirin or non-aspirin NSAID use conferred risk reductions for dysplastic Barrett's oesophagus, regardless of the control series. We excluded effect modification by known risk factors as an explanation for these null findings. We found little support for an inverse association between use of NSAIDs and Barrett's oesophagus. The question of whether or not these medications prevent the onset of Barrett's oesophagus remains open.

The Association Between Aspirin/Nonsteroidal Anti-inflammatory Drugs and Pancreatic Cancer Revisited: An Updated Meta-analysis

Purpose: The association between aspirin (ASA)/ other nonsteroidal antiinflammatory drugs (NSAIDs) and pancreatic cancer remains controversial. A meta-analysis done in 2007 showed no association, but recent evidence continues to point to a possible protective effect of prolonged aspirin use on the risk of pancreatic cancer. The aim of this study was to incorporate recent evidence in an updated meta-analysis on the strength and direction of the association. Methods: Two reviewers independently conducted a systematic search of the Cochrane Library, MEDLINE and PubMed database from 1960 to April 2011. Search terms included aspirin, NSAIDs, anti-inflammatory drugs combined with pancreatic and/or gastro-intestinal cancers. Identified articles were reviewed for additional references. Only studies reporting an effect measure for the association between ASA and/or other NSAIDs and pancreatic cancer were eligible for inclusion. In addition to overall effect of ASA/NSAIDs, subgroup analysis by study design(prospective vs retrospective), study setting(USA vs Other countries), duration of exposure (less than or greater than 5 years) and by exposure type (ASA vs. other NSAIDs) were also performed. Analysis was done using the fixed effect model after a preliminary analysis showed no evidence of heterogeneity among all studies and subgroups. Publication bias was assessed using the Begg and Egger tests and visual inspection of funnel plot. All analyses were done using STATA 11. Results: Fourteen (nine prospective and five retrospective) studies were included in the analysis. The overall pooled effect estimate for both ASA and/or NSAID use was 0.99 (95% CI 0.95-1.04). There was no significant association seen in the subgroup analysis by 1) study design: prospective (RR 0.99, 95% CI 0.94, 1.04), retrospective (RR 1.01, 95% CI 0.85, 1.20); 2) setting: USA(RR 0.98, 95% CI 0.92, 1.04), Other Countries (RR 1.01, 95% CI 0.93, 1.09); 3) duration of exposure: less than or 5 years (RR 0.97, 95% CI 0.87, 1.07), More than 5 years (RR 1.12, 95CI 0.91, 1.39); and 4) type of exposure: ASA (0.98, 95% CI 0.92, 1.03), NSAIDs (RR 1.03, 95% CI 0.94, 1.12). Table 1 summarizes the overall and subgroup analysis results.Table 1: . No Caption available.Conclusion: Currently available evidence suggests that there is no association between ASA/other NSAIDs use and risk of pancreatic cancer. This result is not influenced by duration or type of exposure, and study design or country of study.

Quantifying nonsteroidal anti-inflammatory drug (NSAID) risk: can combining the evidence with the use of a network meta-analysis provide a solution?

Quantifying nonsteroidal anti-inflammatory drug (NSAID) risk: can combining the evidence with the use of a network meta-analysis provide a solution?

Exposure to Non-Steroidal Anti-Inflammatory Drugs during Pregnancy and the Risk of Selected Birth Defects: A Prospective Cohort Study

BackgroundSince use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs.Methods and FindingsWe used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0–12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4–1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9–15.7).ConclusionsExposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded.

Comment on «Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction. A Nationwide Cohort Study»

BackgroundDespite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI). Methods and resultsPatients ≥30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment). ConclusionsEven short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.

Comentário a «Duração do tratamento com anti-inflamatórios não esteroides e impacto no risco de morte e recorrência de enfarte do miocárdio em pacientes com enfarte do miocárdio prévio. Um estudo de coorte Nacional»

Background Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI). Methods and results Patients ≥ 30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment). Conclusions Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MIin patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.

Blood Pressure and Cardiovascular Outcomes in Patients Taking Nonsteroidal Antiinflammatory Drugs

The increased thrombotic cardiovascular (CV) risk in trials of cyclo-oxygenase-2 (COX-2) inhibitors versus placebo, and the apparent similar risk with nonsteroidal antiinflammatory drugs (NSAIDs), may be related to their potential to elevate blood pressure (BP). We evaluated the relationship between baseline BP and change in BP on CV events (CVEs) in patients receiving NSAIDs or COX-2 inhibitors in the prospective randomized, double-blind, Multinational Etoricoxib and Diclofenac Arthritis Long-term Program (N = 34,701) comparing etoricoxib 60 or 90 mg or diclofenac 150 mg daily for a mean duration of 18 months. The main outcome measure was confirmed thrombotic CVEs. The Antiplatelet Trialists' Collaboration endpoint, all-cause mortality, CV/congestive heart failure (CHF) mortality, and CHF incidence were similarly evaluated. We found that baseline systolic BP (SBP) was associated with significantly higher risk of all events (P < 0.001). Baseline diastolic BP (DBP) was inversely and significantly associated with risk of all events (P < 0.001 to P = 0.016) except CV/CHF mortality (P = 0.054). There was no significant differential effect between etoricoxib and diclofenac in relation to CVEs, except for confirmed CHF, for which the risk was significantly higher with etoricoxib (P = 0.019). Only CHF risk (P = 0.020 for both SBP and DBP change), but not thrombotic endpoints, was significantly associated with change in BP from months 0 to 4. These findings were not meaningfully altered after covariate adjustment for baseline CV risk. Baseline BP, but not change in BP, was significantly associated with risk of thrombotic CVEs through 18 months. The CV risk of COX-2s and NSAIDs did not appear to be related to the BP-elevating effects of these agents, although such analyses, i.e., from randomized controlled trials, are unable to definitively exclude such a relationship.

Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction

Background— Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI). Methods and Results— Patients ≥30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment). Conclusions— Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.

Nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol for acute musculoskeletal injuries: Physiotherapists' understanding of which is safer, more effective, and when to initiate treatment

Physiotherapists are primary care practitioners, and are often the first health professional to consult with patients presenting with acute sprains or strains, and such patients may ask for advice regarding medications. Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) are readily available without a prescription and are commonly used by patients. The aim of this study was to investigate New Zealand physiotherapists' knowledge regarding the comparative safety, effectiveness, and appropriate timing of paracetamol and NSAIDs for acute musculoskeletal sprains and strains. A questionnaire was mailed to all members of the New Zealand Society of Physiotherapists currently practicing in the field of musculoskeletal physiotherapy (n = 948). Of 278 respondents (29.3%), just over half (52%) thought that NSAIDs were more effective than paracetamol in the treatment of sprains and strains. Almost half (45%) believed that NSAIDs should be withheld because of the potential for interrupting the beneficial role of inflammation in healing and that NSAIDs could increase bleeding into the injured tissue. In contrast, the majority of respondents (81%) recognised that there was no need to withhold paracetamol in the initial postinjury period. Knowledge regarding safety, effectiveness, and risks of paracetamol and NSAIDs may assist physiotherapists to recommend appropriate management of acute musculoskeletal injuries, within regulatory boundaries.

Meta-analysis: non-steroidal anti-inflammatory drug use and the risk of esophageal squamous cell carcinoma

The relationship between non-steroidal anti-inflammatory drug (NSAID) use and esophageal squamous cell carcinoma (ESCC) has remained unclear. To evaluate the relationship between NSAID use and risk of ESCC, we searched the MEDLINE, Biosis, Web of Science and ISI proceedings databases up to September 2010, together with a manual search of reference lists of relevant articles. Studies evaluating the association between exposure to NSAIDs and risk of ESCC were included. The analyses used random-effect or fixed-effect model based on homogeneity analysis. Seven studies (six case-control studies and one nested case-control study) were included in this meta-analysis. NSAID use was associated with a reduced risk of ESCC (odds ratio = 0.58, 95% confidence interval = 0.47 to 0.72). Specific analysis for aspirin and non-aspirin NSAIDs yielded similar results. There was a protective association between NSAIDs and ESCC. This finding warrants more prospective studies evaluating the relationship between NSAIDs and ESCC.

Balancing the Risks and Benefits of Proton Pump Inhibitors

Balancing the Risks and Benefits of Proton Pump Inhibitors