• acemetacin
• basic amino acids
• co-amorphous
• gastric ulcer

• JYTZD2023142 Key Research Projects of the Liaoning Provincial Department of Education
• XLYC2203044 Liaoning Revitalization Talents Program
• 2021BEG02039 Ningxia Key Research and Invention Program
• YQ202113 Outstanding Youth Lifting Program in the Shenyang Pharmaceutical University

• adverse drug events
• drug-related problems
• drug–drug interactions
• older adults
• potentially inappropriate medications

Although neurological/ophthalmologic side effects including headache, vertigo, somnolence, paresthesia, optic neuritis, and optic neuropathy are listed as side effects in the medication guidelines for ibuprofen, transient tunnel vision and altered consciousness after a single dose of ibuprofen have not been reported. The patient was a 48-year-old man who experienced sudden-onset tunnel vision for a few seconds, followed by an altered state of consciousness for 20 minutes, during which he was communicating with his boss in an altered manner, 15 minutes after having taken 200 mg of ibuprofen. After awakening, he required 2 to 3 hours to return to his premorbid condition. No tongue biting or secessus occurred. Because his blood pressure, blood tests, blood gas analysis, electrocardiography, and electroencephalography results were normal and cerebral magnetic resonance imaging only showed non-specific spots in the subcortical white matter, the condition was attributed to ibuprofen. This case shows that a single dose of ibuprofen can cause severe side effects in the form of tunnel vision and altered consciousness. In some patients, single doses of ibuprofen may cause severe side effects.

• Non-steroidal anti-inflammatory drug
• adverse reaction
• altered consciousness
• hallucination
• headache
• side effect

• Chronic Low Back Pain
• Gastrointestinal Bleeding
• Nonsteroidal Anti-Inflammatory Drugs
• Osteoarthritis

• aspirin
• bleeding peptic ulcer
• cardiovascular disease
• non-steroidal anti-inflammatory drugs
• portal hypertension

• Anticoagulants
• Antithrombotics
• Aspirin
• Atrial fibrillation
• Bleeding
• Warfarin

• adverse drug reactions
• cyclo-oxygenase 2 inhibitors
• gastrointestinal events
• meta-analysis
• nonsteroidal anti-inflammatory drugs

• anti-inflammatory agents
• non-steroidal
• pharmacoepidemiology

• Anti-inflammatory agents
• Elderly
• Glomerular filtration rate
• NSAID
• Risk
• Sweden

• Adult
• Analgesics/administration & dosage
• Breast Implantation/methods
• Bupivacaine/administration & dosage
• Cohort Studies
• Drug Therapy, Combination
• Female
• Humans
• Intraoperative Care/methods
• Ketorolac/administration & dosage
• Liposomes
• Mammaplasty/methods
• Middle Aged
• Pain Management/methods
• Pain Measurement
• Pain, Postoperative/drug therapy
• Pain, Postoperative/prevention & control
• Prognosis
• Retrospective Studies
• Risk Assessment
• Treatment Outcome

• U54 GM104940 NIGMS NIH HHS

• Coxibs
• NSAIDs
• Tuberculosis

Empirical data of medication-related hospitalization are very limited. We aimed to investigate the associations between 12 high risk medication categories (diabetic agents, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, antiplatelets, antihypertensives, antiarrhythmics, anticonvulsants, antipsychotics, antidepressants, benzodiazepine (BZD)/Z-hypnotics, and narcotics) and unplanned hospitalizations. A population-based case–time–control study was performed using Taiwan’s National Health Insurance Research Database. Patients who experienced an unplanned hospitalization (index visit) were identified as index subjects and matched to a randomly selected reference visit within users of a specific category of high-risk medication. An unplanned hospitalization was defined as a hospital admission immediately after an emergency department visit. Discordant exposures to the high-risk medication during the case period (1–14 days before the visit) and the control period (366–379 days before the visit) were examined in both index and reference visits. Antipsychotics was associated with the highest risk of unplanned hospitalizations (adjusted OR: 1.54, 95% CI [1.37–1.73]), followed by NSAIDs (1.50, [1.44–1.56]), anticonvulsants (1.34, [1.10–1.64]), diuretics (1.24, [1.15–1.33]), BZD/Z-hypnotics (1.23, [1.16–1.31]), antidepressants (1.17, [1.05–1.31]) and antiplatelets (1.16, [1.07–1.26]). NSAIDs and narcotics were associated with the highest risks of unplanned hospitalizations with a length of stay ≥10 days. These medication categories should be targeted for clinical and policy interventions.

To assess the prevalence of possible risk factors of upper gastrointestinal bleeding (UGIB) and their age-group specific trend among the general population and osteoarthritis patients.

We utilized data from the National Health Insurance Service that included claims data and results of the national health check-up program. Comorbid conditions (peptic ulcer, diabetes, liver disease, chronic renal failure, and gastroesophageal reflux disease), concomitant drugs (aspirin, clopidogrel, cilostazol, non-steroidal anti-inflammatory drugs, steroid, anticoagulants, and SSRI), personal habits (smoking, and alcohol consumption) were considered as possible UGIB risk factors. We randomly imputed the prevalence of infection in the data considering the age-specific prevalence of Helicobacter pylori (H. pylori) infection in Korea. The prevalence of various UGIB risk factors and the age-group specific trend of the prevalence were identified. Prevalence was compared between osteoarthritis patients and others.

A total of 801926 subjects (93855 osteoarthritis patients) aged 20 and above were included. The prevalence of individual and concurrent multiple risk factors became higher as the age increased. The prevalence of each comorbid condition and concomitant drug were higher in osteoarthritis patients. Thirty-five point zero two percent of the overall population and 68.50% of osteoarthritis patients had at least one or more risk factors of UGIB. The prevalence of individual and concurrent multiple risk factors in younger age groups were also substantial. Furthermore, when personal habits (smoking, and alcohol consumption) and H. pylori infection were included, the prevalence of concurrent multiple risk factors increased greatly even in younger age groups.

Prevalence of UGIB risk factors was high in elderly population, but was also considerable in younger population. Patient with osteoarthritis was at higher UGIB risk than those without osteoarthritis. Physicians should consider individualized risk assessment regardless of age when prescribing drugs or performing procedures that may increase the risk of UGIB, and take necessary measures to reduce modifiable risk factors such as H. pylori eradication or lifestyle counseling.

• Upper gastrointestinal bleeding
• Prevalence
• Risk factor
• General population
• Osteoarthritis

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Alcohol Drinking/adverse effects
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Anticoagulants/adverse effects
• Anticoagulants/therapeutic use
• Comorbidity
• Female
• Gastrointestinal Hemorrhage/epidemiology
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/isolation & purification
• Humans
• Male
• Middle Aged
• Osteoarthritis/drug therapy
• Peptic Ulcer/epidemiology
• Platelet Aggregation Inhibitors/adverse effects
• Platelet Aggregation Inhibitors/therapeutic use
• Precision Medicine
• Prevalence
• Republic of Korea/epidemiology
• Risk Assessment
• Risk Factors
• Selective Serotonin Reuptake Inhibitors/adverse effects
• Selective Serotonin Reuptake Inhibitors/therapeutic use
• Sex Factors
• Smoking/adverse effects
• Young Adult

• Contraindications
• Drug safety
• Interactions
• Musculoskeletal pain
• Non-steroidal anti-inflammatory drugs

• Antipsychotic agents
• Case-crossover
• Diabetes mellitus
• Older people
• Pharmacoepidemiology

• Acute pain
• Ambulatory surgery
• Day surgery
• Dipyrone
• EQ-5D
• Functional Recovery Index
• Metamizole
• NSAID
• Postoperative pain
• Recovery

Nicorandil is a vasodilatory drug used to relieve angina symptoms. Several healthcare products regulatory agencies have issued a warning associating the use of nicorandil and gastrointestinal (GI) ulceration. We aimed to evaluate the association between use of nicorandil and GI ulceration/perforation. A population-based cohort study involving 1 million randomly sampled participants in Taiwan’s National Health Insurance Research Database was carried out. We estimated the association between use of nicorandil and GI ulceration/perforation by a Cox proportional hazards regression model. A nicorandil-specific propensity score (PS) was also created for adjustment of 75 covariates and matching. 25.8% (183/710) of nicorandil-treated patients developed new GI ulcer events and 1.6% (20/1254) developed new GI perforation events in the three-year follow-up period, as compared to 9.3% (61,281/659,081) and 0.3% (2,488/770,537) in the general population comparator cohort. Patients treated with nicorandil were at significantly increased risk of GI ulcer (PS adjusted hazard ratio 1.43, 95% CI, 1.23 to 1.65, 6848 excess cases per 100,000 person years) or GI perforation (aHR 1.60, 95% CI 1.02–2.51, 315 excess cases per 100,000 person years) compared with the nicorandil unexposed population. Our finding may warn the clinicians to weigh the overall risk-benefit balance of nicorandil treatment in patients.

• Consensus
• Endoscopy
• Esophageal and Gastric Varices/complications
• Esophageal and Gastric Varices/therapy
• Gastrointestinal Hemorrhage/complications
• Gastrointestinal Hemorrhage/therapy
• Humans
• National Health Programs
• Risk Factors
• Taiwan

Famotidine given at a dose of 80 mg/day is effective in preventing NSAID-induced gastropathy. The aim of this proof of concept study was to compare twice a day (BID) vs 3-times a day (TID) administration of this total dose of famotidine on intragastric pH in healthy volunteers.

Two analyses were undertaken: (1) a 13 subject controlled cross-over 24-h intragastric pH evaluation of the BID and TID administration of 80 mg/day of famotidine, as well as measures for drug accumulation over 5 days (EudraCT, number 2006-002930-39); and (2) a pharmacokinetic (PK)/pharmacodynamic (PD) model which predicted steady-state famotidine plasma concentrations and pH of the two regimens.

For the cross-over study, gastric pH was above 3.5 for a mean of 20 min longer for TID dosing compared to BID dosing on Day 1. On Day 5, the mean time above this threshold was higher with the BID regimen by ∼25 min. For pH 4, subjects’ gastric pH was above this pH value for a mean of 25 min longer for TID dosing compared to BID dosing on Day 1. For Day 5, the pH was above 4 for ∼45 min longer with the TID regimen as compared with the BID regimen. The mean 24-h gastric pH values when taken in the upright position trended higher for the TID dosing period compared to the BID regimen on Day 1. The steady-state simulation model indicated that, following TID dosing, intragastric pH will be above 3 for 24 h vs 16 h for the BID regimen. There was no evidence for plasma accumulation of famotidine with TID dosing as compared to BID dosing from either analysis.

The data indicate that overall more time is spent above the acidic threshold pH values when 80 mg/day of famotidine is administered TID vs BID. Key limitations included small study size with a short duration and lack of a baseline examination, but was compensated for by the cross-over and PK/PD modeling design. Although most of the comparisons in this proof of concept study were not statistically significant these results have important implications for future research on gastric acid lowering agents used for the prevention of NSAID-induced gastropathy.

• Famotidine
• Gastropathy
• Intragastric
• NSAID
• Prophylaxis
• pH

Older people often need comprehensive treatment, including many medications, and polypharmacy is common. The aims of this cross-sectional investigation were to examine the potentially inappropriate medication during the hospitalization and to identify the factors that may influence such inappropriateness among elderly in Italy.

A sample of 605 individuals aged 65 years and older admitted in non-academic public acute care hospitals was randomly selected. Prescription of inappropriate medications were evaluated during the period from the day of admission to a randomly preselected day (index day). Beers Criteria were used to evaluate appropriateness.

At least one potentially inappropriate medication prescription from the day of hospital admission to the index day has been observed in 188 patients (31.1%), and respectively 84.1% and 15.9% of them had received one or two inappropriate medications. A total of 15 medications was prescribed inappropriately to these 188 patients, for 215 times with a total of 1143 doses. The multivariate logistic regression analysis revealed that the significant predictors for having at least one potentially inappropriate medication prescription during the hospitalization were: patients having an elementary education level, a lower pre-admission performance-based measure of basic activities of daily living, having received an inappropriate drug before the hospitalization, a hospital stay in the general and in the specialties surgical wards, a longer length of hospital stay from the admission to the index day, and having received a higher number of drugs from the day of the hospital admission to the index day. The most prevalent inappropriate medications administered were ketorolac (27.4%), amiodarone (19.1%), and clonidine (11.2%).

This study supports the need for clinical guidelines implementation to assist physicians in choosing the most appropriate drugs for the elderly and for effective education of all physicians.

• Helicobacter pylori
• cyclooxygenase
• gastrointestinal haemorrhage
• nonsteroidal anti-inflammatory agents
• oesophageal and gastric varices
• peptic ulcer

• Anti-Inflammatory Agents, Non-Steroidal/chemistry
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Female
• Fenamates/pharmacology
• Humans
• Mefenamic Acid/chemistry
• Mefenamic Acid/pharmacology
• Pain/drug therapy

Background: The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs; however, there is little information on the risk associated with some NSAIDs and on the impact of risk factors. These data are necessary to evaluate the benefit-risk of individual NSAIDs for clinical and health policy decision making. Within the European Community’s Seventh Framework Programme, the Safety Of non-Steroidal anti-inflammatory drugs (NSAIDs) [SOS] project aims to develop decision models for regulatory and clinical use of individual NSAIDs according to their GI and cardiovascular safety.

Objective: The aim of this study was to conduct a systematic review and meta-analysis of observational studies to provide summary relative risks (RR) of upper GI complications (UGIC) associated with the use of individual NSAIDs, including selective cyclooxygenase-2 inhibitors.

Methods: We used the MEDLINE database to identify cohort and case-control studies published between 1 January 1980 and 31 May 2011, providing adjusted effect estimates for UGIC comparing individual NSAIDs with non-use of NSAIDs. We estimated pooled RR and 95% CIs of UGIC for individual NSAIDs overall and by dose using fixed- and random-effects methods. Subgroup analyses were conducted to evaluate methodological and clinical heterogeneity between studies.

Results: A total of 2984 articles were identified and 59 were selected for data abstraction. After review of the abstracted information, 28 studies met the meta-analysis inclusion criteria. Pooled RR ranged from 1.43 (95% CI 0.65, 3.15) for aceclofenac to 18.45 (95% CI 10.99, 30.97) for azapropazone. RR was less than 2 for aceclofenac, celecoxib (RR 1.45; 95% CI 1.17, 1.81) and ibuprofen (RR 1.84; 95% CI 1.54, 2.20); 2 to less than 4 for rofecoxib (RR 2.32; 95% CI 1.89, 2.86), sulindac (RR 2.89; 95% CI 1.90, 4.42), diclofenac (RR 3.34; 95% CI 2.79, 3.99), meloxicam (RR 3.47; 95% CI 2.19, 5.50), nimesulide (RR 3.83; 95% CI 3.20, 4.60) and ketoprofen (RR 3.92; 95% CI 2.70, 5.69); 4–5 for tenoxicam (RR 4.10; 95% CI 2.16, 7.79), naproxen (RR 4.10; 95% CI 3.22, 5.23), indometacin (RR 4.14; 95% CI 2.91, 5.90) and diflunisal (RR 4.37; 95% CI 1.07, 17.81); and greater than 5 for piroxicam (RR 7.43; 95% CI 5.19, 10.63), ketorolac (RR 11.50; 95% CI 5.56, 23.78) and azapropazone. RRs for the use of high daily doses of NSAIDs versus non-use were 2-3 times higher than those associated with low daily doses.

Conclusions: We confirmed variability in the risk of UGIC among individual NSAIDs as used in clinical practice. Factors influencing findings across studies (e.g. definition and validation of UGIC, exposure assessment, analysis of new vs prevalent users) and the scarce data on the effect of dose and duration of use of NSAIDs and on concurrent use of other medications need to be addressed in future studies, including SOS.

• aged
• osteoarthritis
• analgesics
• adverse drug events

• Acetaminophen/adverse effects
• Acetaminophen/therapeutic use
• Age Factors
• Aged
• Analgesics, Non-Narcotic/adverse effects
• Analgesics, Non-Narcotic/therapeutic use
• Analgesics, Opioid/adverse effects
• Analgesics, Opioid/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Chemical and Drug Induced Liver Injury/etiology
• Frail Elderly
• Humans
• Osteoarthritis/drug therapy
• Risk Factors

• R01 AG034056 NIA NIH HHS
• R01 AG027017 NIA NIH HHS
• R01 NR010135 NINR NIH HHS
• R01 HS018721 AHRQ HHS
• R01 HS017695 AHRQ HHS
• R01HS018721 AHRQ HHS
• K12 HS019461 AHRQ HHS
• K07AG033174 NIA NIH HHS
• K07 AG033174 NIA NIH HHS
• P30 AG024827 NIA NIH HHS
• R56 AG027017 NIA NIH HHS
• P30AG024827 NIA NIH HHS
• R01AG034056 NIA NIH HHS
• R56AG 027017 NIA NIH HHS
• R01 AG028050 NIA NIH HHS
• R01AG028050 NIA NIH HHS
• T32 AG021885 NIA NIH HHS