Risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis.

OBJECTIVE: To examine the risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large real-world ankylosing spondylitis (AS) cohort. METHODS: This nationwide population-based cohort study used data from the Korean National Health Insurance Database. Patients aged ≥18 years old who were newly diagnosed with AS without prior cardiovascular disease between January 2010 and December 2018 were included in this study. Controls without AS were randomly selected by age, sex, and index year. The primary outcome was cardiovascular disease, a composite outcome of ischemic heart disease, stroke, or congestive heart failure. Long-term use of NSAIDs was defined as use of NSAIDs for >365 cumulative defined daily doses. The association between long-term use of NSAIDs and incident cardiovascular disease was examined in both AS and non-AS populations. RESULTS: Among 19 775 patients with AS and 59 325 matched controls without AS, there were 1,663 and 4,308 incident cases of cardiovascular disease, showing an incidence of 16.9 and 13.8 per 1,000 person-years, respectively. Long-term use of NSAIDs was associated with increased risk of cardiovascular disease in non-AS controls (adjusted hazard ratio [aHR], 1.64; 95% CI, 1.48-1.82). In contrast, long-term use of NSAIDs did not increase the risk of cardiovascular disease in AS patients (aHR, 1.06; 95% CI, 0.94-1.20; adjusted for age, sex, socioeconomic status, body mass index, smoking status, hypertension, diabetes, hyperlipidemia, and tumor necrosis factor inhibitor use). CONCLUSION: Prolonged NSAID treatment in AS patients may not be as harmful as in the general population regarding cardiovascular risk.

Structural disease modification in axial spondyloarthritis.

"Disease modification" in axial spondyloarthritis (axSpA) seeks to not only alleviate clinical symptoms but also alter the disease's natural course by impeding new bone formation. Recent years have witnessed the effectiveness of treatments, including biologics and nonsteroidal anti-inflammatory drugs, in managing axSpA symptoms. Emerging evidence points toward their potential impact on slowing structural disease progression. This comprehensive review centers on the pivotal role of inhibiting new bone formation in axSpA disease modification. It delves into the significance of imaging techniques for assessing disease progression and explores the disease-modifying properties of available axSpA treatments, encompassing NSAIDs, TNF inhibitors, IL-17 inhibitors, and JAK inhibitors. This article offers valuable insights into the evolving landscape of disease modification strategies in axial spondyloarthritis, highlighting the multifaceted approaches used to attain these objectives.

Comparison of different nonsteroidal anti-inflammatory drugs for cesarean section: a systematic review and network meta-analysis.

BACKGROUND: Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery. METHODS: CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis. RESULTS: We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs. CONCLUSIONS: Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.

The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study.

Purpose: To investigate whether interindividual variability in the CYP2C9 (*2 and *3 alleles) and VKORC1 (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD >0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI). Results: For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41-174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70-556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the CYP2C9 and VKORC1 genes. No synergism was identified. Conclusion: Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user.

Effect of the combination of diuretics, renin-angiotensin-aldosterone system inhibitors, and non-steroidal anti-inflammatory drugs or metamizole (triple whammy) on hospitalisation due to acute kidney injury: A nested case-control study.

PURPOSE: Concomitant use of diuretics, renin-angiotensin-aldosterone system (RAAS) inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as 'triple whammy' (TW), has been associated with an increased risk of acute kidney injury (AKI). Nevertheless, there is still uncertainty on its impact in hospitalisation and mortality. The aim of the study was to analyse the association between exposure to TW and the risk of hospitalisation for AKI, all-cause mortality and the need for renal replacement therapy (RRT). METHODS: A case-control study nested in a cohort of adults exposed to at least one diuretic or RAAS inhibitor between 2009 and 2018 was carried out within the Pharmacoepidemiological Research Database for Public Health Systems (BIFAP). Patients hospitalised for AKI between 2010 and 2018 (cases) were matched with up to 10 patients of the same age, sex and region of Spain who had not been hospitalised for AKI as of the date of hospitalisation for AKI of the matching case (controls). The association between TW exposure versus non-exposure to TW and outcome variables was analysed using logistic regression models. RESULTS: A total of 480 537 participants (44 756 cases and 435 781 controls) were included (mean age: 79 years). The risk of hospitalisation for AKI was significantly higher amongst those exposed to TW [adjusted odds ratio (aOR) 1.36, 95% confidence interval (95%CI) 1.32-1.40], being higher with current (aOR 1.60, 95%CI 1.52-1.69) and prolonged exposure (aOR 1.65, 95%CI 1.55-1.75). No significant association was found with the need of RRT. Unexpectedly, mortality was lower in those exposed to TW (aOR 0.81, 95%CI 0.71-0.93), which may be influenced by other causes. CONCLUSION: Vigilance should be increased when diuretics, RAAS inhibitors, and NSAIDs or metamizole are used concomitantly, especially in patients at risk such as elderly patients.

Impact of lifestyle and socioeconomic position on use of non-steroidal anti-inflammatory drugs: A population-based cohort study.

PURPOSE: Lifestyle and socioeconomic position may confound the link between non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events, if associated with NSAID use. We examined this association. METHODS: We conducted a cohort study of all adult first-time responders to the Danish National Health Surveys of 2010, 2013, or 2017 without an NSAID prescription within 3 months before survey completion (n = 407 395). Study exposures were weight, smoking status, alcohol consumption, binge drinking frequency, physical activity level, marital status, highest achieved level of education, income, and employment status. We used a Cox model to compute hazard ratios of time to first redemption of an NSAID prescription and a cumulative odds model to compute odds ratios (ORs) of redeeming one additional NSAID prescription in the year after survey completion. RESULTS: Total follow-up time was 1 931 902 years. The odds of redeeming one additional NSAID prescription in the year after survey completion varied within all categories of lifestyle and socioeconomic position. The largest ORs were observed within categories of weight (1.70, 95% CI: 1.65-1.74 for obesity vs. normal weight), smoking status (1.24, 95% CI: 1.21-1.27 for current vs. never use), and education (1.44, 95% CI: 1.39-1.49 for primary or other vs. university or higher education). The Cox model showed consistent results. CONCLUSIONS: Markers of unhealthy lifestyle and low socioeconomic position were associated with initiation and prolonged NSAID use. Consideration of lifestyle and socioeconomic markers as potential confounders in NSAID studies is therefore recommended.

Prescription medication use of United States military service members by therapeutic classification.

Background: This cross-sectional study investigated the prevalence of, and factors associated with, filled prescription medications (FPMs) among United States (US) service members (SMs). Methods: A stratified random sample of active duty SMs from the Air Force, Army, Marine Corps, and Navy was obtained from military workforce records. Participants (n = 26,680) completed a questionnaire on demographics, physical characteristics, and lifestyle factors and approved access to their FPM for the previous 6 months. FPMs were obtained from the military Pharmacy Data Transaction Service that included all prescription medications dispensed at military medical treatment facilities, abroad, at retail pharmacies in the US, and/or through mail-order programs. Results: About two-thirds (65%) of SMs had ≥1 FPM in the 6 months surveillance period. Central nervous system (CNS) agents had the highest prevalence (41%), followed by anti-infective agents (20%), eye/ear/nose/throat preparations (20%), gastrointestinal drugs (18%), autonomic drugs (17%), skin and mucous membrane agents (13%), antihistamine drugs (12%), respiratory tract agents (12%) and cardiovascular drugs (9%). Among CNS agents, overall prevalence of dispensed non-steroidal anti-inflammatory drug (NSAIDs) was 30%. The odds of any FPM was independently associated with female gender, older age, higher body mass index, former tobacco use (smoking and smokeless tobacco), lower alcohol consumption, and was highest among Army, lowest among Marine Corps personnel. Conclusion: In this sample of SMs, dispensing of prescription medication was high, especially NSAIDs, but dispensing of cardiovascular drugs was much lower compared to the general US population, likely because of the younger age and higher level of physical activity of SMs.

Reduced risk of NSAID-Induced adverse events with concomitant use of misoprostol (MICRO study).

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used medications for pain, even though they increase the risk for adverse cardiovascular events. OBJECTIVES: The objective of this study was to determine cardiovascular, cerebrovascular, and renal event rates between NSAIDs versus NSAIDs plus misoprostol. METHODS: A population-based historical cohort of U.S. veterans receiving prescription NSAIDs (1,681,609) versus NSAIDs plus misoprostol (5972 misoprostol users) was followed for 5 years. In an intent-to-treat analysis, NSAID and NSAID plus misoprostol groups were compared using propensity score-weighted Poisson regression models to estimate incident rate ratio (IRR) and Cox regression to estimate hazard ratio (HR). RESULTS: The most prescribed NSAIDs were diclofenac and ibuprofen. The mean follow-up was 35.2 ± 14.5 months. There were 439 total cardio-renal events (5.62/1000 patient-months) in the NSAID group and 419 patients (5.01/1000 patient-months) in the NSAID plus misoprostol group (Hazard Ratio (HR): 0.89; 95% confidence interval [CI]: 0.78-1.019; p = 0.09). The risk of cardiovascular event was lower in the NSAID plus misoprostol group (HR: 0.56; 95% CI: 0.34-0.93; p < 0.0001). Cerebrovascular event rates were lower in the NSAID plus misoprostol group (HR: 0.74; 95% CI: 0.60-0.94, p < 0.0001) and for renal (HR: 0.67; 95% CI: 0.49-0.89, p < 0.0001) events. All-cause mortality rate was not different between the two groups (HR: 1.05; 95% CI: 0.88-1.25, p = 0.61). CONCLUSION: Compared with NSAID use alone, the concomitant use of NSAID plus misoprostol is associated with a reduced risk of NSAID-induced cardiovascular, cerebrovascular, and renal adverse events. These data support the development of a safer NSAID when combined with misoprostol.

Aspirin versus placebo on estrogen levels in postmenopausal women: a double-blind randomized controlled clinical trial.

BACKGROUND: Estrogen is involved in the pathogenesis of breast and gynecological cancers. Regular use of aspirin reduces estrogen levels. The present study aimed to evaluate the effect of aspirin on estrogen levels in postmenopausal women. METHODS: This double-blind, placebo-controlled parallel-group trial was conducted on postmenopausal women referred to an outpatient clinic at a women's hospital in Tehran. Volunteers were randomly assigned to receive aspirin 100 mg/day or placebo for 6 weeks. Estradiol, sex hormone-binding globulin (SHBG), and testosterone levels at baseline and at the end of the intervention were measured by ELISA. Data were analyzed using SPSS 20, Kolmogorov-Smirnov test, independent samples t-test, and Mann-Whitney U test. RESULTS: Twenty-seven and 28 participants were finally analyzed in the aspirin and placebo groups, respectively. There was no significant difference between the two groups in body mass index (BMI), age, or menopausal years. There was a statistically significant difference (p = 0.002) in the amount of  change in estradiol levels of the intervention group (median=- 3.5 pg/ml) compared to the control group (median=1.5 pg/ml). In contrast, there were no significant differences between the two groups regarding testosterone and SHBG levels (p = 0.58, p = 0.32). CONCLUSIONS: Since low doses of aspirin may decrease estradiol levels, it could be considered a promising adjunctive therapeutic candidate in postmenopausal women to decrease BC incidence. However, further studies with larger sample sizes, measurements of estrogen levels and its related compounds in different time points accompanied by long-term follow-ups are needed to better elucidate the potential mechanisms by which nonsteroidal anti-inflammatory drugs (NSAIDs) negatively affect breast cancer. TRIAL REGISTRATION: IRCT201012195397N1. Date of first registration: 03/01/2011.

Primary Dysmenorrhea: Pathophysiology, Diagnosis, and Treatment Updates.

Primary dysmenorrhea (PD) is a common, disregarded, underdiagnosed, and inadequately treated complaint of both young and adult females. It is characterized by painful cramps in the lower abdomen, which start shortly before or at the onset of menses and which could last for 3 days. In particular, PD negatively impacts the quality of life (QOL) of young females and is the main reason behind their absenteeism from school or work. It is suggested that increased intrauterine secretion of prostaglandins F2α and E2 are responsible for the pelvic pain associated with this disorder. Its associated symptoms are physical and/or psychological. Its physical symptoms include headache, lethargy, sleep disturbances, tender breasts, various body pains, disturbed appetite, nausea, vomiting, constipation or diarrhea, and increased urination, whereas its psychological symptoms include mood disturbances, such as anxiety, depression, and irritability. While its diagnosis is based on patients' history, symptoms, and physical examination, its treatment aims to improve the QOL through the administration of nonsteroidal anti-inflammatory drugs, hormonal contraceptives, and/or the use of non-pharmacological aids (e.g., topical heat application and exercise). Patients must be monitored to measure their response to treatment, assess their adherence, observe potential side effects, and perform further investigations, if needed.

Oral nonsteroidal anti-inflammatory drugs as treatment of joint and muscle pain in temporomandibular disorders: A systematic review.

OBJECTIVE: To evaluate pain control in patients with joint and muscle pain in temporomandibular disorder (TMD) diagnosis treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: The systematic research was conducted via Pubmed, Scopus, Web of Science, Google Scholar, and Cochrane databases. RESULTS: Four full-text randomized-controlled trials (RCTs) were considered eligible. This systematic review included 164 patients whose VAS scores were assessed before and after therapy. In the selected studies, a strong heterogeneity in the diagnosis and in the use of different types and prescriptions of NSAIDs was highlighted. These limitations had to be considered to understand whether a clinical recommendation could be made. Eventually, all patients treated with NSAIDs showed an improvement in pain. CONCLUSION: The use of oral NSAIDs as the first approach to control joint and muscle pain is sustained by the current scientific literature, but further investigations on this topic are still needed.

Acute Kidney Injury associated with "Triple whammy" combination: a protocol for a systematic review.

Background: "Triple whammy" (TW) refers to the simultaneous use of diuretics, renin-angiotensin-aldosterone system inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs). To date, the risk of developing acute kidney injury (AKI) associated to this combination has not been deeply investigated. The objectives are to analyze the incidence of AKI associated to the exposure to "triple whammy" including all NSAIDs versus non-exposure to this combination. Secondarily, the risk of hospitalization, severe adverse events, requirement of renal replacement therapy and mortality will be assessed. Also, the incidence of AKI associated to the exposure to "triple whammy" versus non-exposure will be analyzed, including only metamizole as NSAID.   Methods: A systematic literature search of intervention studies and analytical observational studies will be conducted in the Cochrane Library, Medline and EMBASE, among others. AKI 12 months after the last prescription of the triple combination will be the main outcome. Relative frequencies, risk of bias and certainty of evidence will be analyzed. Additionally, sensitivity and subgroup analyses will be performed.   Results: Once this systematic review has been completed, the results are expected to provide an estimate of the risk associated with this triple combination and the renal variables, in addition to new guidance on the renal treatment of patients potentially receiving triple therapy.  Conclusions: This is intended to be the first systematic review of observational studies to analyse TW combination and AKI's risk based on well-validated epidemiological databases exploring drug safety issues.

Effect of postoperative non-steroidal anti-inflammatory drugs on anastomotic leakage after pancreaticoduodenectomy.

BACKGROUND: Although the association between an increase in anastomotic leakage (AL) and non-steroidal anti-inflammatory drugs (NSAIDs) has been reported in gastrointestinal surgeries, this issue has rarely been addressed for pancreaticoduodenectomy (PD). We aimed to investigate the association between postoperative NSAIDs administration and clinically relevant AL (CR-AL) following PD. METHODS: We retrospectively evaluated 2,163 consecutive patients who underwent PD between 2007 and 2019. The patients were divided into two groups; patients who received and did not receive NSAIDs by postoperative day (POD) 5. We conducted a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the baseline differences between both groups. We compared the occurrence of CR-AL and other postoperative outcomes before and after IPTW. Further, we used the multivariable binary logistic regression method for a sensitivity analysis for CR-AL. RESULTS: A total of 2,136 patients were included in the analysis. Of these, 222 (10.4%) received NSAIDs by POD 5. The overall occurrence rate of CR-AL was 14.9%. After IPTW, postoperative NSAIDs were significantly associated with CR-AL (odds ratio [OR]: 1.24, 95% CI [1.05, 1.47], P = 0.012), prolonged postoperative hospitalization (OR: 1.31, 95% CI [1.14, 1.50], P < 0.001), and unplanned readmission within 30 days postoperatively (OR 1.48: 95% CI [1.15, 1.91], P = 0.002). However, this association was not consistent in the sensitivity analysis. CONCLUSIONS: Postoperative NSAIDs use was significantly associated with an increase in CR-AL incidence following PD. However, sensitivity analysis failed to show its association, which precludes a firm conclusion of its detrimental effect.

Granulocyte and monocyte/macrophage apheresis for the treatment of immune-mediated inflammatory arthropathies: case reports.

Drug therapy of immune-mediated inflammatory arthropathies is not always satisfactory, and there is a risk of adverse events. Granulocyte and monocyte/macrophage apheresis (GMA) is a non-pharmacological therapeutic option that is beneficial and very well tolerated. GMA involves passing blood through a column with cellulose acetate beads to remove increased and activated myeloid lineage cells and improve the cytokine profile. The technique reduces pain and inflammation. We present four clinical reports that illustrate the clinical uses of GMA with the medical device Adacolumn® in patients with different backgrounds and immune-mediated inflammatory arthritis. The results were positive, and no adverse events were reported.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Tolerability, and Safety of Celecoxib Oral Solution (ELYXYB) in Acute Treatment of Episodic Migraine with or without Aura.

BACKGROUND: Safe, effective, oral therapies are needed for acute treatment of migraine. This clinical trial assessed the efficacy, tolerability, and safety of celecoxib oral solution (ELYXYB) in a single migraine attack associated with moderate-to-severe pain. METHODS: This was a phase III, randomized (1:1), double-blind, placebo-controlled trial, conducted at 41 US centers from December 2016 to October 2017. Adults with episodic migraine (with or without aura) for ≥1 year were treated with a single 4.8 mL dose of 120-mg celecoxib oral solution or placebo. Co-primary endpoints were the proportion of patients who were pain-free and free from the most bothersome migraine symptom (MBS) at 2 hours post-dose. The MBS was identified at screening from among nausea, photophobia, or phonophobia. RESULTS: Six hundred thirty-one patients were randomized (celecoxib oral solution, n=316; placebo, n=315; mean age 41 years, range 18-75; 84.3% female). One study site met prespecified outlier criteria (defined as a treatment effect estimate that was at least twice as large as all other sites) and was excluded from efficacy analyses. This site had a mean 2-hour pain freedom placebo response rate of 75% vs a combined mean of 23.5% for all other sites. In subsequent analysis, 2-hour post-dose pain freedom response rates were significantly higher in the celecoxib oral solution group vs placebo (32.8%, [27.2%, 38.8%]) vs 23.5%, [18.5%, 29.2%]; P=0.020). For 2-hour post-dose MBS freedom, response rates were significantly higher in the celecoxib oral solution group vs placebo (58.1% [51.4%, 64.5%] vs 43.9% [37.2%, 50.7%]; P=0.003). A total of 10.7% (31/289) of patients treated with celecoxib oral solution and 9.9% (28/283) of placebo-treated patients reported a treatment-emergent adverse event (TEAE). Study drug-related TEAEs were reported by 7.3% (21/289) and 7.4% (21/283) of celecoxib oral solution and placebo patients, respectively; the most common were nausea (celecoxib oral solution: 1.4% [4/289] vs placebo: 1.8% [5/283]) and dysgeusia (celecoxib oral solution: 1.7% [5/289] vs placebo: 1.1% [3/283]). No serious TEAEs, deaths, or drug-related TEAEs leading to withdrawal were reported. CONCLUSION: Celecoxib oral solution is a safe, effective COX-2-selective nonsteroidal anti-inflammatory drug for the treatment of acute migraine. In this analysis, celecoxib oral solution was significantly more effective than placebo and was also associated with a low rate of gastric TEAEs. Celecoxib oral solution may provide a convenient, alternate option to currently available treatments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03009019; registered January 4, 2017; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03009019.

Recurrence rate and risk factors for recurrence after thoracoscopic surgery for primary spontaneous pneumothorax: A nationwide population-based study.

PURPOSE: This large-scale nationwide population-based study aimed to determine the recurrence rate and risk factors for recurrence after video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax (PSP). METHODS: This retrospective study used data from the Taiwan National Health Insurance Database to identify individuals who underwent VATS for PSP from 2007 to 2014. All patients were followed up until December 31, 2017. Study variables included demographic characteristics, intensive care unit admission, lung resection status, use of non-steroidal anti-inflammatory drugs (NSAIDs), and hospital level. The primary outcome was 1-year recurrence, and the secondary outcomes were the 1-year rate of reintervention for recurrence and overall recurrence rate. RESULTS: During the study period, 6654 patients underwent VATS for PSP (average age: 23.2 years, 89.1% male), including 910 patients (13.7%) who experienced recurrence within 1 year and 531 patients (8.0%) who required reintervention within 1 year. The overall recurrence rate was 24.8%, with an average follow-up time of 6.7 years. Age ≤18 years and the use of NSAIDs, especially ketorolac, were significant risk factors for 1-year recurrence and overall recurrence. Younger age was a risk factor for 1-year reintervention. In subgroup analysis, NSAID use was a significant risk factor for 1-year recurrence, 1-year reintervention, and overall recurrence in pediatric patients but not in adult patients. CONCLUSIONS: In Taiwan, the 1-year recurrence rate was 13.7% after VATS for PSP. Younger age and the use of NSAIDs, especially ketorolac, were significant risk factors for short- and long-term recurrence after VATS for PSP.

Does the administration of meloxicam before head and neck radiotherapy reduce the risk of mandibular osteoradionecrosis? An animal model study.

OBJECTIVE: To assess whether the administration of meloxicam before head and neck radiotherapy reduces the risk of mandibular osteoradionecrosis in rats. MATERIAL AND METHODS: Sixty male Wistar rats were randomly divided into 6 groups (n = 10) according to the meloxicam administration and radiation therapy: control (C), irradiated (I), single dose of meloxicam (M1), single dose of meloxicam and irradiated (M1I), triple dose of meloxicam (M3), triple dose of meloxicam and irradiated (M3I). Meloxicam was administrated (20 mg/kg per dose) 1 h before the radiation therapy (single dose of 20 Gy) and 24 h and 48 h after the radiation therapy for groups with two additional doses. Ten days after the radiation therapy, the three right mandibular molars were extracted from all rats, who were euthanatized after 21 or 35 days (n = 5 per group). The mandibles were assessed by macroscopic evaluation and micro-CT analysis. RESULTS: The right hemimandibles of the irradiated groups revealed macroscopic signs of osteoradionecrosis, and those of the non-irradiated groups revealed complete gingival healing. A significant delay in alveolar socket healing in all irradiated groups was observed in the micro-CT assessment regardless meloxicam treatment. CONCLUSION: The administration of meloxicam before head and neck radiotherapy does not reduce the risk of mandibular osteoradionecrosis when associated to dental extractions. CLINICAL RELEVANCE: Since meloxicam has been shown to be a potential radiation-protective agent, and osteoradionecrosis physiopathology is believed to be related to an inflammatory process, possible interactions are relevant to be investigated.

Management of urinary tract infections: what do doctors recommend and patients do? An observational study in German primary care.

BACKGROUND: Uncomplicated urinary tract infections (UTIs) in women are usually managed in primary care with antibiotics. However, many women seem to prefer to handle UTI symptoms with nonsteroidal anti-inflammatory drugs (NSAIDs) and other remedies. The aim of this study was to compare UTI management as recommended by physicians with the patients' management at home. METHODS: This prospective cohort study in German primary care is based on clinical data from local practices and patient questionnaires. Participating women completed a baseline data sheet in the practice; their urine sample was tested by a dipstick in the practice and cultured by a laboratory. The women reported treatment and symptom-related impairment on an eight-item symptom questionnaire daily for 7 days. Using growth curve models, we analysed the influence of time on the total severity score to examine how symptoms changed across days. We then examined whether symptom severity and symptom course differed between patients who took antibiotics or NSAIDs. RESULTS: A total of 120 women (mean age of 43.3 ± 16.6 years) were enrolled. The urine dipstick was positive for leucocytes in 92%, erythrocytes in 87%, and nitrites in 23%. Physicians prescribed antibiotics for 102 (87%) women and recommended NSAIDs in 14 cases. According to the women's reports, only 60% (72/120) took antibiotics, while the remainder took NSAIDs and other remedies. Symptoms declined from day 0 to day 6, irrespective of whether women decided to take an antibiotic, NSAIDs, none or both, as confirmed by a significant curvilinear time effect (B = 0.06, SE = 0.005, p < .001). The symptom course, however, was moderated by taking antibiotics so that the change in symptom severity was somewhat more pronounced in women taking antibiotics (B = 0.06) than in the remainder (B = 0.04). CONCLUSION: A substantial proportion of women did not follow their physicians' treatment recommendations, and many used NSAIDs. All women had a good chance of recovery irrespective of whether they decided to take antibiotics. A sensitive listening to patient preferences in the consultation may encourage physicians to recommend and prescribe symptomatic treatment with NSAID more often than antibiotic medicines.

Clinical Guidelines for Drug-Related Peptic Ulcer, 2020 Revised Edition.

Korean guidelines for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer were previously developed in 2009 with the collaboration of the Korean College of Helicobacter and Upper Gastrointestinal Research and Korean Society of Gastroenterology. However, the previous guidelines were based mainly upon a review of the relevant literature and expert opinion. Therefore, the guidelines need to be revised. We organized a guideline Development Committee for drug-related peptic ulcer under the auspices of the Korean College of Helicobacter and Upper Gastrointestinal Research in 2017 and developed nine statements, including four for NSAIDs, three for aspirin and other antiplatelet agents, and two for anticoagulants through a de novo process founded on evidence-based medicine that included a literature search and a meta-analysis, A consensus was reached through the application of the modified Delphi method. The primary target of these guidelines is adult patients undergoing long-term treatment with NSAIDs, aspirin or other antiplatelet agents and anticoagulants. The revised guidelines reflect the expert consensus and is intended to assist clinicians in the management and prevention of druginduced peptic ulcer and associated conditions.