Optimising pediatric paracetamol and ibuprofen use: a retrospective study with expert evaluation of efficacy, safety, and healthcare costs

This study aims to compare use and costs of anti-secretory and cardiovascular co-medication in osteoarthritis patients treated with selective or non-selective NSAIDs. A retrospective study examined Belgian patients aged 65 years or more who suffer from osteoarthritis and are chronic users of selective NSAIDs (n=1,376) or non-selective NSAIDs (n=8,482). A before-and-after analysis compared drug use and costs between period 1 (first 6 months of 2002) and period 2 (several 1-year periods stretching over 2003-2004). A cohort analysis contrasted patients taking selective NSAIDs with patients taking non-selective NSAIDs. Anti-secretory co-medication included histamine H2-receptor antagonists and proton pump inhibitors. Cardiovascular co-medication referred to cardiac glycosides, anti-arrhythmics, anti-thrombotics, anti-angina drugs, anti-hypertensive drugs and serum-lipid-reducing drugs. Volume of drug use was expressed as number of packages and costs were computed in Euro. The volume of anti-secretory co-medication increased by 36% with selective NSAIDs and by 55% with non-selective NSAIDs between periods 1 and 2. Cardiovascular co-medication rose by 18% with selective NSAIDs and by 12% for non-selective NSAIDs. Focusing on patients who did not take anti-secretory co-medication in period 1, patients taking selective NSAIDs were just as likely to start anti-secretory co-medication in period 2 as patients taking non-selective NSAIDs (odds ratio: 1.05; 95% confidence interval: 0.90-1.23). Patients taking selective NSAIDs were just as likely to start cardiovascular co-medication as patients taking non-selective NSAIDs (odds ratio: 1.03; 95% confidence interval: 0.78-1.36). Annual costs of treating osteoarthritis in ambulatory care amounted to 756 <euro> with selective NSAIDs and 416 <euro> with non-selective NSAIDs. This originated from higher acquisition costs (278 <euro> vs. 24 <euro>) and higher costs of co-medication (477 <euro> vs. 392 <euro>) with selective NSAIDs. The use of selective and non-selective NSAIDs is accompanied by a higher use of co-medication over time. The increase in anti-secretory co-medication was more prominent with non-selective NSAIDs. The rise in cardiovascular co-medication was more pronounced with selective NSAIDs. Treatment of osteoarthritis with selective NSAIDs is more expensive than with non-selective NSAIDs in terms of acquisition costs and costs of co-medication.

Management of fever in children: Summary of the Italian pediatric society guidelines

Background Prior epidemiologic studies have shown an inverse relationship of aspirin and NSAID use with breast cancer (BC) risk in the general population. Women with benign breast disease (BBD) are at an increased BC risk compared with women in the general population, and we have shown that BBD biopsies contain increased numbers of immune cells compared with normal breast tissues donated for research in the Komen Tissue Bank. We hypothesized that NSAID use among women with BBD is associated with reduced risk of BC. Methods We evaluated BC risk in relation to aspirin and NSAID use in a single institution retrospective cohort of 4,498 women who received a biopsy diagnosis of BBD between 1/1/1992 and 12/31/2001. Information on usual medication use, including average number of days used per month (0, 1-7, 8-28 and &amp;gt;28), was collected via questionnaires mailed after identification of participants. NSAIDs were categorized into three classes: 1) Aspirin, 2) Ibuprofen (plus other prostaglandin synthesis inhibitors), and 3) COX inhibitors. BC events were captured via medical record, questionnaires, and Tumor Registry records. Medication use was evaluated for associations with clinical and pathology features. Hazard ratios (HR) and 95% confidence intervals (CI) examining associations between medication use and BC risk were estimated using Cox regression analyses, with adjustment for age and BMI at biopsy, years between biopsy and questionnaire, and pathologic features related to BC risk (severity of BBD and degree of involution in background lobules). Tests for trend examining frequency of use were calculated from ordered values (lowest to highest) in Cox models with a one degree-of-freedom linear term. We assessed BC associations with any type of NSAID use, as well as the three subclasses. Results Information on NSAID use was available for 3,089 (69%) of the participants in the cohort; these women had a median age of 49 and did not differ in BC risk from women who did not provide data on NSAID use (p=0.46). Of the 3,089 respondents, 313 (10.1%) subsequently developed BC with median follow-up of 17 years. Age was significantly associated with use of all types of NSAIDs, with increasing use in older women. BMI at the time of biopsy, severity of BBD findings, and involution in background lobules were also associated with NSAID use; thus these factors and age were adjusted for in risk association analyses. Ever users of NSAIDs (any type) had a significantly lower risk of BC than never users (HR 0.76, CI 0.59-0.98, p=0.03), and increasing frequency of NSAID use was significantly associated with lower BC risk (HRs 0.81, 0.79, and 0.70 for regular use 1-7, 8-28, and &amp;gt;28 days/month), trend p=0.02. Analyses of drug classes revealed that ever use of ibuprofen (HR 0.61, CI 0.42-0.89, p=0.01) and ever use of COX inhibitors (HR 0.59, CI 0.39-0.89, p=0.01) were associated with decreased BC risk. COX inhibitors in particular showed a strong dose response effect with increasing use (HRs 0.97, 0.52, and 0.47 for regular use 1-7, 8-28, and &amp;gt;28 days/month), trend p&amp;lt;0.01. Use of aspirin was not associated with BC risk (HR 0.88, CI 0.64-1.21, p=0.44). Conclusions In this exploratory analysis, we found use of ibuprofen and other NSAIDs to be associated with decreased BC risk among women who had undergone a BBD biopsy. These findings suggest that anti-inflammatory approaches may have value in chemoprevention among women with BBD. Citation Format: Amy Degnim, Robert Vierkant, Stacey Winham, Marlene Frost, Daniel Visscher, Jodi Carter, Suneetha Kaggal, Julie Cunningham, Teresa Allers, Tanya Hoskin, Ethan Heinzen, Celine Vachon, Keith Knutson, Keith Knutson, Derek Radisky, Mark Sherman. NSAID use and breast cancer risk in a retrospective cohort of women with benign breast disease [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-06.

This study sought to evaluate inappropriate prescribing practices in an atrial fibrillation (AF) population, as outlined by the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults with Atrial Fibrillation or Atrial Flutter document. The 2016 AF quality measures document specified medications to avoid in certain AF populations, including aspirin and anticoagulant combination therapy in patients without cardiovascular disease, and non-dihydropyridine calcium channel blockers in patients with reduced ejection fraction. Using data from the NCDR PINNACLE registry, a national outpatient cardiology practice registry, we assessed rates of inappropriate prescription of two types of medications among AF outpatients from 5/1/2008-5/1/2016. Overall rates of inappropriate prescription and variation by practice were calculated. Patient and practice factors associated with inappropriate prescription were assessed in adjusted analyses. A total of 107,759 of 658,250 (16.4%) patients without cardiovascular disease were inappropriately prescribed an antiplatelet and anticoagulant together, and 5,731 of 150,079 (3.8%) patients with reduced ejection fraction were inappropriately prescribed a non-dihydropyridine calcium channel blocker. Overall, 14.8% of AF patients were prescribed medications that were not recommended. Both patient and practice factors were associated with inappropriate prescribing, and the adjusted practice-level median odds ratio for inappropriate prescription was 1.70 (95% CI: 1.61-1.82), indicating a 70% likelihood that 2 random practices would treat identical AF patients differently. In a large registry of AF patients treated in cardiology practices, overall rates of inappropriate prescription practices, as defined by the 2016 AF quality measures, were relatively low, but significant practice variation was present.

Current enhanced recovery guidelines suggest that opioid sparing medications should be used for analgesia whenever possible following colorectal surgery. The present study aims to assess whether post-operative NSAID use is associated with an increased anastomotic leak rate after a colonic or rectal anastomosis. A systematic review was performed for studies investigating anastomotic leak rate following NSAID use vs control after colonic or rectal anastomosis. Meta-analysis was performed to assess for overall risk of anastomotic leak with NSAID use, as well as sub-group analysis to compare selective vs non-selective NSAIDs and drug-specific NSAID safety profiles. Seven studies were included in the final review. Use of an NSAID post-operatively was associated with an overall increased risk of anastomotic leakage [OR 1.58 (1.23, 2.03), P = 0.0003]. Non-selective NSAIDs were associated with an increased risk [OR 1.79 (1.47, 2.18), P < 0.00001], but selective NSAIDs were not. The non-selective NSAID diclofenac was associated with an increased leak rate [OR 2.79 (1.96, 3.96), P < 0.00001], but ketorolac was not [OR 1.36 (0.89, 2.06), P = 0.16]. Great caution must be taken when prescribing NSAIDs following colonic or rectal anastomotic creation. The safety profile varies within the NSAID class and further research is needed to clarify which NSAIDs are safe for use and which are not.

Objective To investigate adverse events(ADEs) associated with the use of paracetamol and ibuprofen in people under 18 years of age. Background The use of NSAIDs reached a peak as a result of the spread of COVID-19 in previous years. Minors, as a special population, need to pay more attention to the use of corresponding drugs and the occurrence of adverse events (ADEs). Methods ADEs report data of the two drugs were extracted from the FDA Adverse Event Reporting System(FAERS) from the first quarter of 2014 to the third quarter of 2022. Results The use of the two drugs in this population was primarily associated with injury, poisoning and surgical complications. The psychiatric disorders produced by the use of acetaminophen(12.6%) and ibuprofen(9.2%) in the adolescent group were significantly higher than those in the other age groups. The use of acetaminophen in the four age groups involved hepatobiliary disorders was more significantly (10.3%, 8.1%, 9.1%, 11.5%), while the use of ibuprofen was more obviously involved in renal and urinary disorders(5.0%, 6.2%, 9.6%, 7.1%). Conclusions The use of acetaminophen and ibuprofen in children of different age groups has different characteristics. Pediatric clinical pharmacists can provide medication monitoring to minimize ADEs based on these characteristics.

The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. However, following their introduction into the market, concerns have developed regarding their safety, particularly their cardiovascular safety. The purpose of this study was to assess the cardiovascular risk (events included were myocardial infarction, stroke and myocardial infarction-related deaths) associated with long-term (>180 days of exposure) and short-term (<or=180 days of exposure) use of non-selective NSAIDs, including 'preferential COX-2 inhibitors' (i.e. etodolac, nabumetone and salsalate), and selective COX-2 inhibitors. A retrospective analysis of the Veterans Integrated Service Network 17 Veterans Affairs (VA) database was conducted. Medicare data and Texas Department of Health mortality data were incorporated to capture events occurring outside the VA healthcare network. Patients >or=35 years of age who received celecoxib, rofecoxib, ibuprofen, etodolac and naproxen from 1 January 1999 through 31 December 2001, were included. Multivariate Cox proportional hazard models were used to analyse the relationship between cardiovascular risk and NSAID use, including selective COX-2 inhibitor use, while adjusting for various risk factors. We identified 12 188 exposure periods (11 930 persons) and 146 cardiovascular events over the entire study period. Compared with long-term ibuprofen use, long-term use of celecoxib (adjusted hazard ratio [HR] 3.64; 95% CI 1.36, 9.70) and rofecoxib (adjusted HR 6.64; 95% CI 2.17, 20.28) was associated with a significant increase in cardiovascular risk. When restricted to patients >or=65 years of age, the cardiovascular risks associated with long-term celecoxib (adjusted HR 7.36; 95% CI 1.62, 33.48) and rofecoxib (adjusted HR 13.24; 95% CI 2.59, 67.68) use increased. Short-term use of celecoxib (adjusted HR 0.75; 95% CI 0.42, 1.35) and rofecoxib (adjusted HR 0.85; 95% CI 0.39, 1.86) was not associated with any significant change in cardiovascular risk when compared with short-term ibuprofen use. Neither long- nor short-term exposure to naproxen and etodolac was associated with cardionegative or cardioprotective effects when compared with ibuprofen use. The findings of this observational study, along with recent clinical trial results, suggest that prolonged exposure to selective COX-2 inhibitors may be associated with an increased risk of adverse cardiovascular outcomes.

Advisors Call for No New Heart Warnings for NSAIDs

BackgroundAntibiotic consumption is increasing worldwide, particularly in low and middle-income countries (LMICs). Access to lifesaving antibiotics in LMICs is crucial while minimising inappropriate use. Studies assessing the economic impact of inappropriate antibiotic use in LMICs are lacking. We explored the economic impact of inappropriate antibiotic use using the example of upper respiratory tract infections (URIs) in Ghana, as part of the ABACUS (AntiBiotic ACcess and USe) project.MethodsA top-down, retrospective economic impact analysis of inappropriate antibiotic use for URIs was conducted. Two inappropriate antibiotic use situations were considered: (1) URIs treated with antibiotics, against recommendations from clinical guidelines; and (2) URIs that should have been treated with antibiotics according to clinical guidelines, but were not. The analysis included data collected in Ghana during the ABACUS project (household surveys and exit-interviews among consumers buying antibiotics), scientific literature and stakeholder consultations. Included cost types related to health care seeking behaviour for URIs. Additionally, cost saving projections were computed based on potential effects of future interventions that improve antibiotic use.ResultsHealth care costs related to inappropriate antibiotic use for URIs were estimated to be around 20 million (M) USD annually, including 18 M USD for situation 1 and 2 M USD for situation 2. Travel costs and lost income due to travel, together, were estimated to be around 44 M USD for situation 1 and 18 M USD for situation 2. Possible health care cost savings range from 2 to 12 M USD for situation 1 and from 0.2 to 1 M USD for situation 2.ConclusionsThis study indicates that inappropriate antibiotic use leads to substantial economic costs in a LMIC setting that could have been prevented. We recommend investment in novel strategies to counter these unnecessary expenditures. As the projections indicate, this may result in considerable cost reductions. By tackling inappropriate use, progress can be made in combatting antibiotic resistance.

To review the rationale for and the potential clinical benefits of an early approach to viral acute respiratory infections with NSAIDs to switch off the inflammatory cascade before the inflammatory process becomes complicated. It has been shown that in COVID-19 as in other viral respiratory infections proinflammatory cytokines are produced, which are responsible of respiratory and systemic symptoms. There have been concerns that NSAIDs could increase susceptibility to SARS-CoV-2 infection or aggravate COVID-19. However, recent articles reviewing experimental research, observational clinical studies, randomized clinical trials, and meta-analyses conclude that there is no basis to limit the use of NSAIDs, which may instead represent effective self-care measures to control symptoms. The inflammatory response plays a pivotal role in the early phase of acute respiratory tract infections (ARTIs); a correct diagnosis of the cause and a prompt therapeutic approach with NSAIDs may have the potential to control the pathophysiological mechanisms that can complicate the condition, while reducing symptoms to the benefit of the patient. A timely treatment with NSAIDs may limit the inappropriate use of other categories of drugs, such as antibiotics, which are useless when viral cause is confirmed and whose inappropriate use is responsible for the development of resistance.

The Inappropriate Use of Imaging Studies: A Report of the 2004 Intersociety Conference

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently dispensed nonprescription drugs in community pharmacies. However, inappropriate use of NSAIDs by consumers has been associated with development of gastrointestinal (GI) injuries and renal injuries. Community pharmacists’ education of consumers on proper use of NSAIDs and their associated adverse effects has been shown to reduce the GI and renal injuries. In Qatar, no studies have been done to assess the community pharmacists’ knowledge, attitude, and practices related to renal and GI adverse effects of NSAIDs. Therefore, this study aimed to assess Qatar community pharmacists’ knowledge, attitude, and practices on the safe use of nonprescription NSAIDs to reduce the risk of kidney and GI injuries. MethodsA cross-sectional web-based survey was conducted among community pharmacists in Qatar. A pre-tested 28-item questionnaire that was developed through a multi-phase iterative process was administered to a convenient sample of community pharmacists in Qatar. Data were analyzed using descriptive and inferential statistics with statistical significance set at p < 0.05. ResultsOverall, 114 community pharmacists responded to the online questionnaire (response rate 15.2%). Approximately 90% of the community pharmacists demonstrated from good to excellent knowledge on the renal and GI adverse effects of NSAIDs, with none of their sociodemographic and professional characteristics having a significant effect on their knowledge scores. More than half of the pharmacists reported that they always or usually educated patients on the dosage (98.6%), administration (95.8%), side effects and precautions (78%), and contraindications (71.2%) of NSAIDs during their routine practices. The majority of the pharmacists had positive attitude towards educating patients about adverse effects of NSAIDs, as well as identifying high-risk patients who should avoid nonprescription NSAIDs. However, 45.7% of the pharmacists strongly agreed or agreed that educating patients about NSAIDs can be time consuming. ConclusionCommunity pharmacists in Qatar demonstrated good knowledge of the renal and GI adverse effects of NSAIDs with some obvious areas of improvement, and this can be reinforced through continuing professional development. They also showed positive attitudes towards protecting patients against the renal and GI adverse effects of NSAID. However, a significant proportion of the pharmacists admitted that educating patients on NSAIDs was time consuming, which is a cause of concern warranting further investigation. Community pharmacy managers should provide community pharmacists adequate time and support to educate individuals at risk of renal and GI injuries who obtain NSAIDs from their pharmacies. Also, the Ministry of Public Health of Qatar should consider making counseling on high-risk medications (e.g., NSAIDs and insulin) by community pharmacists mandatory so that measures can be put in place in the pharmacies to free the pharmacist for education and counseling.

Background: Once daily use of aspirin has been associated with a reduction in risk for cancer and cardiovascular mortality outcomes. More frequent use of aspirin and ibuprofen has not been well studied. We evaluated the association between aspirin and ibuprofen use and risk of all-cause mortality, cancer mortality, and cardiovascular disease mortality within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Methods: Participants included 72,242 male and 70,978 female participants aged 55-74 with no history of cancer at baseline enrolled in the trial between 1993-2001. The frequency of aspirin and ibuprofen use one year prior to baseline was ascertained through self-administered questionnaires and causes of mortality were ascertained by linkage to the National Death Index. Multivariate hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: During follow-up, 14,721 deaths due to all causes, 7,069 deaths due to cancer, and 5,281 deaths due to cardiovascular disease were identified. A J-shaped risk curve for all-cause mortality was observed among exclusive aspirin users compared to those not taking either aspirin or ibuprofen. Although reductions in risk for mortality were observed among individuals who reported using aspirin less than daily (HR=0.90, 95%CI: 0.84-0.96 for all-cause mortality), a significant increase in risk for all-cause mortality (HR=1.21; 95% CI 1.12-1.31), cancer mortality (HR=1.12; 95% CI 0.99-1.25), and cardiovascular mortality (HR=1.23; 95% CI 1.09-1.40) was observed among individuals who reported taking aspirin more than once daily. The significant elevation in risk for all-cause mortality among exclusive aspirin users remained (HR=1.17; 95% CI 1.05-1.29) even after exclusion of deaths within the first six years of follow-up. Similar reductions in risk for mortality outcomes were observed for daily or less than daily use of ibuprofen and for the combined use of aspirin and ibuprofen, although no significant elevations in risk were observed overall among individuals who reported using more than once daily. Conclusion: This large prospective analysis observed an inverse association between all mortality outcomes and daily or less than daily use of NSAIDs. Our data did not, however, support a reduction in risk for any mortality outcomes among individuals using NSAIDs more than once daily, and may even suggest an elevation in risk for heavy aspirin users. Citation Format: Sarah E. Daugherty, Sonja I. Berndt, Mark Purdue, Wen-yi Huang. Nonsteroidal anti-inflammatory drugs and all-cause mortality, cancer mortality, and cardiovascular mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B93.

Inappropriate antimicrobial use in Turkish pediatric hospitals: A multicenter point prevalence survey

BackgroundInappropriate visits to emergency departments (EDs) could represent from 20% to 40% of all visits. Inappropriate use is a burden on healthcare costs and increases the risk of ED overcrowding....