Duration Of Nonsteroidal Anti-inflammatory Drugs Use Research Articles

НПВП-гастропатия — скрытая угроза при лечении боли

INTRODUCTION. NSAID gastropathy is one of the possible negative consequences of taking non-steroidal anti-inflammatory drugs (NSAIDs), characterized by pathological changes in the gastrointestinal tract. The disease is often asymptomatic, which is the reason for its low detectability during outpatient appointments. The risks of developing serious complications from the gastrointestinal tract (ulcers, bleeding, perforations) increase 3-fold already in the first days of NSAID use. Even a short course of NSAID therapy lasting 3–5 days carries a risk of gastrointestinal complications similar to that of long-term treatment. As a consequence, prevention strategies should be implemented regardless of the duration of therapy, especially in patients with more than one risk factor. CONCLUSION. The risks of complications when taking this group of drugs can be significantly reduced by drug prophylaxis in patients with risk factors for the development of NSAID-gastropathy. Proton pump inhibitors are the main means of preventing possible adverse drug reactions of NSAIDs from the upper gastrointestinal tract. Physicians should consider the need for prophylactic use of proton pump inhibitors throughout the duration of NSAID use. Omez® 20 mg has indications for both prevention and treatment of NSAID-associated gastropathy and can be recommended to such patients from the first day of NSAID intake regardless of the course duration of NSAID intake. KEYWORDS: pain, gastroenterology, geriatrics, gastrointestinal bleeding, gastrointestinal tract, proton pump inhibitors, neurology, adverse events, nonsteroidal anti-inflammatory drugs, NSAIDs, NSAID-associated complications, NSAID gastropathies, general surgery, prevention, therapy, risk factor, chronic pain

Abstract P2-11-01: Breast cancer (BC) risk among patients with benign breast disease (BBD) by NSAID use

Abstract Background: Approximately one million U.S women are diagnosed with benign breast disease (BBD) annually, which increases breast cancer (BC) risk between 1.5- and four-fold, depending on the pathologic characteristics of the lesion and other factors. BBD lesions are associated with inflammation and fibrosis, suggesting that inflammatory pathways may play a role in progression of BBD to BC. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are well tolerated, widely used drugs that block inflammation by inhibiting cyclooxygenase enzymes, which lowers prostaglandin synthesis, and by exerting numerous additional anti-inflammatory effects. NSAIDs are inversely associated with several types of cancer, including BC in some, but not all studies, and have been linked to lower BC risk among BBD patients in prior publications. We examined the association between NSAID use and BC risk, overall and by self-reported history of BBD, using data from the American Cancer Society Cancer Prevention Study II (CPS-II). Methods: The Cancer Prevention Study-II (CPS-II) Nutrition Cohort is a study of approximately 189,000 U.S. men and women followed prospectively for cancer incidence and mortality. Study participants filled out a detailed questionnaire at baseline in 1992/1993 and follow-up surveys in 1997 and every two years until 2017. On each follow-up survey, participants reported type, quantity, and duration of NSAID use as well as diagnoses of BBD. Incident BCs were either self-reported and validated via medical records or cancer registry linkage, or identified via National Death Index linkage. Women in the analytic cohort were followed from date of 1997 survey until diagnosis of BC, reported use of tamoxifen, report of cancer other than BC, date of death, loss to follow-up or end of follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) assessing associations of BBD and NSAID use with BC risk were estimated using Cox proportional hazards regression analysis. Statistical interactions between BBD and NSAID were evaluated by fitting and testing the corresponding cross-product terms, along with the main effects of each. Both NSAID use and BBD were modeled as time-dependent variables, allowing exposure status to change over the course of the multiple surveys returned. Results: Of the 60,517 women included in the study, 3,899 (6.4%) developed BC. Mean follow-up time was 12.7 years. A total of 23,661 women (39%) reported a diagnosis of BBD at some point during the study period, and 54,656 (90%) reported some NSAID use. Women self-reporting BBD were 46% more likely to develop BC than those without self-reported BBD (HR 1.46, 95% CI 1.36-1.57). Overall, BC risk was not increased among NSAID users versus non-users (HR 0.95, 95% CI 0.88-1.02). In contrast, BC risk was reduced among current NSAID users with a history of BBD (HR 0.87, 95% CI 0.78-0.97), but not among NSAID users who did not report a history of BBD (HR 1.02, 95% CI 0.92-1.13, p-interaction=0.04). Risk did not differ across number of pills per month (RR=0.84 for <15 pills/month, 0.89 for 15-29, 0.88 for 30-44, 0.78 for 45-59, 0.88 for 60+). Conclusion: In our study, NSAID use had a statistically-significant protective effect on BC risk among women with BBD, suggesting its potential use as a chemopreventive agent in this high-risk group of women, but not among those who did not report a history of BBD. Citation Format: Robert A Vierkant, Matthew Masters, Lauren R Teras, Mark E Sherman. Breast cancer (BC) risk among patients with benign breast disease (BBD) by NSAID use [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-01.

Adjunctive therapy for acute musculoskeletal pain

Acute musculoskeletal pain (MSP) is one of the leading complaints at patients' admission. Acute MSP is usually localized in the lower back, neck, shoulder girdles, and shins. With an increase in the number of obese and hypodynamic people, the prevalence of MSP increases, especially lower back pain. Treatment of acute MSP in the back consists of informing the patient about a favorable prognosis of the disease, recommendations to maintain daily activity, primary and additional pharmacotherapy. Primary or main pharmacotherapy of acute MSP in the back includes non-steroidal anti-inflammatory drugs (NSAIDs). Adjunctive therapy is usually used in combination with NSAIDs and is aimed to increase the effectiveness of treatment and reduce the duration of NSAIDs use. As an additional therapy, muscle relaxants or B vitamins can be prescribed. The efficacy and safety of combination therapy of NSAIDs and high-dose complexes of B vitamins have been demonstrated in clinical trials involving patients with acute back pain.

Non-steroidal anti-inflammatory drugs and gastroprotection in primary health care users.

ObjectiveThe aim of this study is to assess the prevalence of gastroprotection and identify the main factors that influence the taking of protective drugs by the adult population treated with non-steroidal anti-inflammatory drugs (NSAID).MethodsThis study was cross-sectional, conducted by including a contingent of 800 users of primary health care services (n=369, 46% males and n=431, 54% females). Included in the study were individuals of both genders aged 18+ who sought counselling or treatment during the three-month period. The data collection of this study was based on the completion of a structured questionnaire, which included questions related to the use of NSAIDs, the way these drugs were prescribed and administered and the simultaneous taking of gastroprotective drugs.ResultsThe prevalence of the gastroprotective drugs use was higher among the elderly, individuals living in urban areas, those with higher education, those with daily use of NSAID, individuals receiving prescriptions from their own doctors, and those suffering from side effects from the use of NSAID, as well as subjects that had a longer duration of NSAID use. Diclofenac was the most prescribed NSAID. Gastric pain and dizziness were the most experienced side effects.ConclusionThis paper demonstrates the need to improve the quality of primary health care service through informing and educating patients regarding the need to take gastro-protective drugs for those at high risk of adverse effects manifested by the use of NSAIDs.

Nonsteroidal Anti-Inflammatory Drugs Impact on the Outcomes of Hospitalized Patients with Clostridium difficile Infection.

PurposeMouse model experiments have demonstrated an increased Clostridium difficile infection (CDI) severity with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) use. We aim to evaluate the impact of NSAIDs in humans after a diagnosis of CDI on primary outcomes defined as I) all-cause mortality and II) toxic mega-colon attributable to CDI.Patients and methodsAll hospitalized patients with a diagnosis of CDI were divided into two groups; those with NSAIDs administered up to 10 days after onset of CDI versus no NSAIDs use. The primary outcomes were analyzed between the groups, while controlling for severity of CDI. A logistic regression analysis was performed to identify the predictors of worse outcomes.ResultsNSAIDs were administered in 14% (n=80) of the 568 hospitalized visits for an average of 2.5 days after the CDI diagnosis. All-cause mortality was high in patients who did not receive NSAIDs as compared to those who did receive NSAIDs (16.6% vs 12.5%, p 0.354). Patients who were prescribed NSAIDs were more likely to have toxic mega-colon as compared to those who were not prescribed NSAIDs (2.5% vs 0.6%, p 0.094). Results were not statistically significant, even after controlling for CDI severity. Logistic regression analysis did not identify NSAIDs administration as a significant factor for all-cause mortality in CDI patients.ConclusionThis retrospective study results, contrary to mouse model, did not show association between NSAID use and CDI related mortality and toxic mega-colon. Shorter duration of NSAIDs use, younger people in study group, and timely CDI treatment may have resulted in contrasting results.

Non-Steroidal Anti-Inflammatory Drug Use and the Risk of Acute Myocardial Infarction in the General German Population: A Nested Case-Control Study.

IntroductionUse of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied.ObjectivesThe aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors.MethodsBased on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004–2009, a nested case–control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers.ResultsOverall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26–2.45), indometacin (1.69, 1.22–2.35), ibuprofen (1.54, 1.43–1.65), etoricoxib (1.52, 1.24–1.87), and diclofenac (1.43, 1.34–1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group (<60 years) and similar for patients with or without major cardiovascular risk factors.ConclusionRelative AMI risk estimates differed among the 15 investigated individual NSAIDs. Diclofenac and ibuprofen, the most frequently used NSAIDs, were associated with a 40–50% increased relative risk of AMI, even for low cumulative NSAID amounts. The relative AMI risk in patients with and without cardiovascular risk factors was similarly elevated.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-017-0113-x) contains supplementary material, which is available to authorized users.

Adverse drug reactions in a primary care population prescribed non-steroidal anti-inflammatory drugs

Objective. To determine how often patients with musculoskeletal (MSK) complaints prescribed a non-steroidal anti-inflammatory drug (NSAID) subsequently consult their general practitioner (GP) with a non-serious adverse drug reaction (ADR). Design. Cohort study. Setting. A healthcare database containing the electronic GP medical records of over 1.5 million patients throughout the Netherlands. Patients. A total of 16 626 adult patients with MSK complaints prescribed an NSAID. Main outcome measures. The patients’ medical records were manually assessed for the duration of NSAID use for a maximum of two months, and consultations for complaints predefined as potential ADRs were identified. Subsequently, the likelihood of an association with the NSAID use was assessed and these potential ADRs were categorized as likely, possible, or unlikely ADRs. Results. In total, 961 patients (6%) consulted their GP with 1227 non-serious potential ADRs. In 174 patients (1%) at least one of these was categorized as a likely ADR, and in a further 408 patients (2.5%) at least one was categorized as a possible ADR. Dyspepsia was the most frequent likely ADR, followed by diarrhoea and dyspnoea (respectively 34%, 8%, and 8% of all likely ADRs). Conclusion. Of the patients with MSK complaints prescribed an NSAID, almost one in 30 patients re-consulted their GP with a complaint likely or possibly associated with the use of this drug. The burden of such consultations for non-serious ADRs should be taken into account by GPs when deciding whether treatment with an NSAID is appropriate.

Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available.

Nonsteroidal Anti-Inflammatory Drug and Aspirin Use in Relation to Lung Cancer Risk among Postmenopausal Women

Results from prospective studies suggest that nonsteroidal anti-inflammatory drugs (NSAID) may decrease lung cancer risk; however, any protective effect appears to be most evident in men. We evaluated the associations between NSAID use and lung cancer incidence in postmenopausal women in the Women's Health Initiative (WHI) adjusting for female-specific potential confounders such as hormone therapy in addition to smoking histories and other potential confounders. We identified 143,841 women from ages 50 to 79 and 1,902 centrally confirmed lung cancer cases were included in the analysis. We used Cox regression models to estimate HRs and their 95% confidence intervals (CI). Compared with nonuse, regular NSAID use was not associated with overall lung cancer incidence (NSAID use >10 years HR 0.87; 95% CI, 0.71-1.08, P(trend) = 0.13). No statistically significant associations were found when examined by histologic subtypes and although there was a trend of decreased risk with longer duration of NSAID use in the adenocarcinoma subtype, this was not statistically significant (NSAID use >10 years HR 0.80; 95% CI, 0.58-1.10; P(trend) = 0.07). Our study did not show that NSAID use is associated with lung cancer risk in women even after adjusting for female-specific confounders. There was a trend of decreased risk in the adenocarcinoma subtype; however, this was not statistically significant. Future studies will need to take in account the various molecular subtypes of non-small cell lung cancer to further elucidate the role of NSAIDs in lung cancer, especially for the adenocarcinoma subtype.

Abstract LB-279: Nonsteroidal anti-inflammatory drug (NSAID) use and risk of lethal renal cell carcinoma

Abstract Background: Studies suggest that non-steroidal anti-inflammatory drug (NSAID) use may increase risk of renal cell cancer (RCC), but the relationship to the lethal form of RCC remains unknown. Methods: We examined the relationship between NSAID use and RCC risk in two large prospective cohorts: the Nurses’ Health Study and the Health Professionals Follow-up Study. Use of aspirin and other NSAIDs was ascertained in 1990 in the Nurses’ Health Study and in 1986 in the Health Professionals Follow-up Study, and every 2 years thereafter. We evaluated baseline use and duration of NSAID use. We defined the lethal form of RCC as RCC that resulted in death due to the disease. Results: During follow-up of 18 years among 77,524 women and 20 years among 49,403 men, we documented 364 cases of RCC, of which 102 were fatal. Regular use of non-aspirin NSAIDs was associated with an increased overall RCC risk; there was a dose-response relationship between duration of non-aspirin NSAID use and RCC risk; compared with non-regular use, the pooled multivariable relative risks (RRs) were 0.78 (95% CI, 0.58-1.06) for use of less than 4 years, 1.29 (95% CI, 0.95-1.74)) for 4 to less than 10 years, and 2.21 (95% CI 1.39-3.49) for use for 10 or more years (P for trend, 0.0006). Furthermore, non-aspirin NSAID users of 4-10 years (pooled multivariable RR 3.13, 95% CI 1.70-5.77) and more than 10 years (pooled multivariable RR 7.23, 95% CI 2.51-20.83) had a significantly increased risk of lethal RCC. Aspirin use was not associated with increased risk of overall (pooled multivariable RR 1.07, 95% CI 0.84-1.34) or lethal RCC (pooled multivariable RR 1.59, 95% CI 0.85-2.96). Conclusion: Our prospective data suggest that non-aspirin NSAID use is associated with an increased incidence of RCC, especially the lethal form of RCC. Citation Format: Mark A. Preston, Jed-sian Cheng, Glen Barrisford, Alex Sanchez, Adam S. Feldman, Dayron Rodriguez, Toni K. Choueiri, Meir Stampfer, Walter C. Willett, Eunyoung Cho. Nonsteroidal anti-inflammatory drug (NSAID) use and risk of lethal renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-279. doi:10.1158/1538-7445.AM2014-LB-279

Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease.

The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease. Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays. Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P=0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P=0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P<0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P=0.018, respectively). The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

Nonsteroidal anti-inflammatory drug use and the risk of melanoma

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have emerged as potential chemopreventive agents for melanoma. However, the clinical studies have provided contradictory results as to whether NSAIDs reduce the risk of melanoma. Our aim was to assess this association through a detailed meta-analysis of the studies on the subject published in the peer-reviewed literature. Relevant studies were identified by searching PubMed, EMBASE and Web of Science electronic databases up to July 2012. Reference lists from retrieved articles were also reviewed. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the fixed-effects or the random-effects models on the basis of heterogeneity analysis. Subgroup analyses were carried out where data were available. Ten studies involving 490 322 participants contributed to the meta-analysis. The summary RR estimate on the basis of all studies did not indicate that overall NSAIDs use significantly decreases the risk of melanoma (RR=0.94; 95% CI, 0.86-1.03). The use of neither aspirin (RR=0.96; 95% CI, 0.89-1.03) nor nonaspirin NSAIDs (RR=1.05; 95% CI, 0.96-1.14) was associated with the risk of melanoma. Similar results were obtained in the subgroup analyses of cohort studies (RR=1.03; 95% CI, 0.95-1.13), high-intensity NSAID use (the highest dose of NSAID use reported by included studies, RR=1.05; 95% CI, 0.79-1.40), and long-term NSAID use (longest duration of NSAID use reported by included studies, RR=0.87; 95% CI, 0.66-1.14). However, a slight reduction in the risk of melanoma by taking NSAIDs was observed in case-control studies (RR=0.86; 95% CI, 0.80-0.93). In conclusion, the results of our meta-analysis did not indicate that the use of NSAIDs or aspirin is associated with the risk of melanoma. More and in-depth research should focus on those problems in the future.

Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: Results from five prospective cohort studies

Animal and pathological studies suggest that inflammation may contribute to amyotrophic lateral sclerosis (ALS) pathology and that non-steroidal anti-inflammatory drugs (NSAIDs) might be protective. However, there are no prospective data on the relation between NSAID use and ALS risk in humans. The relation between NSAID use and ALS risk was explored in five large prospective cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health - AARP Diet and Health Study). Detailed NSAID information was sought from 780,000 participants, 708 of whom developed ALS during follow-up. Cox proportional hazards models were used within each cohort and cohort-specific estimates were pooled with random effects models. Results showed that neither non-aspirin NSAID use, nor aspirin use was associated with ALS risk overall. The multivariable, pooled relative risk was 0.96 (95% CI 0.76-1.22) among non-aspirin NSAID users compared with non-users. Duration of NSAID use in years and frequency of NSAID use were not associated with ALS risk overall. In conclusion, the results do not support an overall effect of NSAIDs on ALS risk, but because NSAIDs have heterogeneous effects, a role of individual compounds cannot be excluded.

Systematic review of small bowel diaphragm disease requiring surgery

To perform a systematic review of all cases of small bowel diaphragm disease requiring surgery. Small bowel diaphragm disease is a rare complication of small bowel enteropathy secondary to the use of non-steroidal anti-inflammatory drugs (NSAIDs). The objective was to determine the presenting symptoms, duration of NSAID use, mode of diagnosis and type of surgery associated with cases of small bowel diaphragm disease requiring surgery. A comprehensive search of the world literature between January 1980 and December 2010 was undertaken. The search terms 'diaphragm disease' and 'mucosal diaphragm disease' in combination with the terms 'surgery', 'intestine' or 'small bowel' were used. All cases of small bowel diaphragm disease requiring surgery in adult patients within the the last 30 years were included. Data including age, gender, mode of presentation, NSAID use, mode of diagnosis, form of surgery, affected area of small bowel and mortality were recorded and analysed. There were 55 cases of small bowel diaphragm disease requiring surgery (31F:18M) with a median age of 69 years. NSAID use occurred in 44 cases and the mean duration of NSAID use was 7 years. The most common presentation was with anaemia in combination with obstructive symptoms. The diagnosis was established by a laparotomy in 51% of cases followed by capsule endoscopy in 25% of cases. Operations performed included small bowel resection (56), combined resection and strictureplasty (three), strictureplasty (one) and hemicolectomy (two). There was only one death. Small bowel diaphragm disease presenting as a surgical emergency is likely to become more common due to the increased use of NSAIDs. A history of NSAID use in patients with iron deficiency anaemia or obstructive symptoms should lead to a high index of suspicion for this condition and should be preoperatively investigated.

Association of Perioperative Use of Nonsteroidal Anti-Inflammatory Drugs With Postoperative Myocardial Infarction After Total Joint Replacement

Use of nonsteroidal anti-inflammatory drug (NSAIDs) analgesics is controversial because of cardiovascular risk, but perioperative use may be advantageous for total joint replacement. Thus, we performed this single-center observational cohort study to determine any association between NSAID use and postoperative myocardial infarction (POMI). All patient admissions undergoing total hip or knee replacement between March 3, 2009, and September 1, 2010, were identified. Nonsteroidal anti-inflammatory drug use was identified. Postoperative myocardial infarction was defined as troponin I level greater than 0.1 ng/mL. Propensity scores were calculated to adjust for bias of receiving NSAIDs and troponin measurements. Propensity scores and other covariates were used in logistic regression to determine the independent association of NSAID use with POMI. Of the 10,873 arthroplasty admissions, 1518 (14%) had serial troponins measured, and 97 had a POMI (0.9%). Incidence of POMI was 0.8% for the 9,831 who received NSAIDs and 1.8% for the 1,042 (10%) admitted patients who did not receive NSAIDs with a risk difference of -1% with 95% confidence interval (CI) of -0.2% to -1.9%. The adjusted odds ratio (0.95; 95% CI, 0.5-1.8) and relative risk (0.95; 95% CI, 0.5-1.8) indicated that NSAIDs were not significantly associated with the risk of POMI. Mean duration of NSAID use was 3 days. Length of stay (98 versus 115 hours) was significantly reduced in the NSAID group. Brief perioperative use of NSAIDs was not associated with increased risk for myocardial infarction after total hip and knee replacement; it may provide benefit in length of stay.

Nonsteroidal anti‐inflammatory drugs

Nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a decreased colorectal cancer (CRC) risk. However, to the best of the authors' knowledge, the effects of NSAID on clinical outcomes after CRC diagnosis are not well defined. The authors investigated the association between prediagnosis NSAID use and mortality after CRC diagnosis among women in the California Teachers Study cohort. Women aged <85 years participating in the California Teachers Study, without a prior CRC diagnosis at baseline (1995-1996), and who were diagnosed with CRC during follow-up through December 2005, were eligible for analysis of the association between prediagnosis NSAID use and mortality. NSAID use (including aspirin and ibuprofen) was collected through a self-administered questionnaire. Cancer occurrence was identified through California Cancer Registry linkage. Multivariate Cox proportional hazards regression models were used to estimate hazards ratios (HR) for death and 95% confidence intervals (95% CIs). Among 621 CRC patients who were identified, 64% reported no prediagnosis regular NSAID use, 17% reported use of 1 to 6 days/week, and 20% reported daily use. A duration of NSAID use <5 years was reported by 17% of patients and a use of >or=5 years was reported by 18%. Regular prediagnosis NSAID use (1-3 days/week, 4-6 days/week, and daily) versus none was associated with improved overall survival (OS) (HR, 0.71; 95% CI, 0.53-0.95) and CRC-specific survival (HR, 0.58; 95% CI 0.40-0.84) after adjustment for clinically relevant factors. Prediagnosis NSAID use >or=5 years (vs none) was found to be associated with improved OS (HR, 0.55; 95% CI, 0.37-0.84) and CRC-specific survival (HR, 0.40; 95% CI, 0.23-0.71) in adjusted analyses. When used regularly or over a prolonged duration before CRC diagnosis, NSAIDs are associated with decreased mortality among female CRC patients.

Are Patients Aware of Upper Gastrointestinal (GI) Side Effects of Nonsteroidal Anti-inflammatory Drugs (NSAIDs)? An Inner City Community Hospital Experience

Purpose: NSAID associated GI side effects are a significant cause of morbidity and mortality. Although much is known about NSAIDs and their GI side effects, little is known about patient awareness of NSAID related upper GI side effects in the United States. The aim of our study was to evaluate patient awareness about NSAID induced upper GI side effects. Methods: A retrospective analysis utilizing a standard questionnaire completed during physician encounter at Interfaith Medical Center, Brooklyn NY from March to May 2009. All patients 18 years of age or older currently taking NSAID or having used NSAID in the last 2 years were included in the study. Those who never used NSAID and critical care patients were excluded. The questionnaire included demographics, co-morbidities, indication and duration of NSAID use and awareness of upper GI side effects. Complications of NSAID such as heartburn, abdominal pain, ulcer, bleeding and perforation were evaluated. There were 130 females and 180 males included in the study. The data was analyzed using regression analysis, t-test, correlation and Chi-square test as indicated. Results: The ages ranged from 18-93 years with mean age of 52 years. African-Americans comprised 88.7% of the study population. Only 15.8% patient had achieved education beyond high school. Motrin was the most commonly used NSAID (41.6%) and 37.7% patients had used two or more types of NSAIDs at different times. 68% of patients were not aware of any upper GI side effects while 32% were aware of some side effects. Of those who were aware of some side effects, only 44% patients knew NSAIDs could cause peptic ulcers and upper GI bleeding. About 50% of patients who were prescribed NSAID claimed that they were not counseled of potential GI side effects. Patients who had used 2 or more types of NSAID were more aware of side effects compared to those taking less than 2 types (p: 0.016). Among those patients who had used multiple NSAIDs, only 30% had been made aware of upper GI side effects (p: 0.009). 37% of patients who claimed they read side effects profile of NSAID were aware of some side effects compared to 14% of those who never read side effects profile (p: 0.04). Only 5 out of 26 patients with PUD were aware of side effects (p: 0.02). There was no statistically significant difference in awareness in terms of education, duration, indications and between patients who were prescribed vs. those who took OTC. Conclusion: Despite the associated significant mortality and morbidity and high cost of treatment, most patients remain unaware of upper GI side effects of NSAID. We can hope that increased patient knowledge of side effects may reduce the incidence and prevalence of GI complications due to these medications.Table

Effect of non‐steroidal anti‐inflammatory drugs on non‐melanoma skin cancer incidence in the SKICAP‐AK trial

Recent studies link the prostaglandin metabolic pathway to skin carcinogenesis expanding possibilities that cyclooxygenase (COX) inhibitors may be utilized in non-melanoma skin cancer (NMSC) chemoprevention. Using data from a study of the efficacy of retinol supplementation on incidence of NMSC, we sought to determine the role of non-steroidal anti-inflammatory drugs (NSAIDs) in NMSC development. Cox proportional hazards models describe the relationship between NSAID use and time to first squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) among participants categorized by use pattern: continuous users (use for length of study duration), new users (use for less than study duration), and non-users. For SCC and BCC, there was a statistically significant protective effect for participants who reported use for less than the study duration (HR = 0.49, 95%CI 0.28-0.87 and HR = 0.43, 95%CI 0.25-0.73, respectively). Categorical examination of NSAIDs (aspirin (ASA) vs. non-ASA NSAIDs) showed significant effects for BCC among those using non-ASA NSAIDs for less than the study duration (HR = 0.33, 95%CI 0.13-0.80). For SCC and BCC, NSAID use of shorter duration and potentially more recent, was more protective than longer duration of use. These results are counter to the idea that longer duration of NSAID use is more protective. Additional investigations are needed into the role NSAIDs play in the chemoprevention of NMSC.

Nonsteroidal anti-inflammatory drug use and breast cancer risk: a Danish cohort study

Epidemiologic studies investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer have yielded conflicting results. We examined the association between use of aspirin and nonaspirin NSAIDs and breast cancer risk among 28 695 women in the Danish Diet, Cancer and Health cohort. Information on NSAID and paracetamol use was obtained from a self-administered questionnaire completed at baseline (1993-1997) and updated through 2003 using a nationwide prescription database. Detailed information on breast cancer incidence and tumour characteristics was obtained from nationwide health registers. Cox proportional hazards regression was used to compute incidence rate ratios (RRs) and 95% confidence intervals (CIs). We identified 847 breast cancer cases over an average follow-up period of 7.5 years. Any NSAID use at baseline was associated with an increased incidence of breast cancer compared with nonuse (RR, 1.27; 95% CI, 1.10-1.45). A similar result was observed for any NSAID use in a combined analysis of baseline and prescription data (1.34; 95% CI, 1.15-1.56). Aspirin-only users experienced a slightly higher breast cancer incidence (RR, 1.38; 95% CI, 1.12-1.69) than exclusive users of nonaspirin NSAIDs (RR, 1.25; 95% CI, 1.04-1.49). Introduction of a lag time of 1 year provided similar results. We found no clear differences in risk estimates with frequency, recency or duration of NSAID use, or by hormone receptor status of the breast tumours. Paracetamol use was unrelated to breast cancer incidence. The increased breast cancer incidence among NSAID users may reflect a noncausal association, but our study provides no evidence of a chemopreventive effect of NSAIDs against breast cancer over the durations studied.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and mammographic density

Mammographic density has been established as a strong risk factor for breast cancer while use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) has been associated with a reduction in risk of breast cancer. The hypothesis is that NSAIDs reverses the expression of prostaglandin E2, thereby reducing the local production of estrogens. This report describes the differences in mammographic densities by duration of NSAID use in a multiethnic population. Information for this analysis was available from two previous investigations: a nutritional intervention study with 218 women and a nested case-control study of breast density with 1274 women. On the basis of self-reported medication use from a questionnaire common to both investigations, women were categorized into no use, up to 1 year, 2-5 years, 6-10 years, and 11+ years. Screening mammograms were assessed for density using a computer-assisted method. We applied general linear models to calculate mean percent densities for each medication use category while adjusting for covariates. The analysis of the overall study population did not show a significant association between total NSAID use and mammographic density. Contrary to our hypothesis, women with long-term total NSAID use had non-significantly higher densities than non-users. In addition, the results differed by menopausal status. Whereas the trend of higher densities with longer duration of total NSAID use was significant among postmenopausal women, breast density was slightly lower among premenopausal women with long-term NSAID use. Experimental studies need to be performed to study the effect, if any, of NSAID use on breast density.