Trends of medication used in patients with pre-ESKD from 2010 to 2018 in Taiwan.

BACKGROUND/PURPOSE: The burden of end-stage kidney disease (ESKD) continues to grow globally. Information on medication prescribed to advanced chronic kidney disease (CKD) patients can help formulate further CKD prevention policies. This study aimed to review and assess several major medications routinely prescribed to pre-ESKD patients. METHODS: Medication information of advanced CKD patients one year before regular dialysis was collected from the National Health Insurance Research Database from 2000 to 2018 in Taiwan. Usages of major medication were comprehensively analyzed. RESULTS: During 2000-2018, trends in medication usage evolved gradually in the pre-ESKD population in Taiwan. The use of erythropoietin had increased (48.3% in 2000 to 71.0% in 2018) with decreased blood transfusion rate (70.9% in 2003 to 52.1% in 2018). The use of non-steroidal anti-inflammatory drugs had also dropped (43.5% in 2004 to 25.5% in 2018). These changes were more evident for patients enrolled in the pre-ESKD prevention program. The most frequently used blood pressure-lowering and glucose-lowering agents were calcium channel blockers (90.6%) and insulin (78.1%), but usage of metformin was unexpectedly high (38.4% in 2018). The most frequently used blood thinner was aspirin (49.5%), with considerably increased use of direct oral anticoagulant (16.5% in 2018). CONCLUSION: An overview of the trends of major medication usage and blood transfusion represented the continuously improving care quality in pre-ESKD patients in Taiwan. These trends were especially evident in patients enrolled in the pre-ESKD prevention program. This report also indirectly indicated the potential and long-term benefits of implementing CKD and pre-ESKD prevention programs.

[Spondyloarthritis in childhood and adulthood]. / Spondyloarthritiden im Kindes- und Erwachsenenalter.

Axial spondylarthritis in adulthood (SpAA) is frequently initially manifested as a sacroiliitis, whereas this not true for enthesitis-related arthritis (EAA), which begins in childhood and adolescence. Classically, EAA begins with peripheral arthritis and only a part transitions into a juvenile SpA (jSpA) or SpAA. The criteria used for classification of SpAA and EAA are currently being validated and revised. For the first time imaging is included for EAA. For both diseases nonsteroidal anti-inflammatory drugs (NSAID) are initially used therapeutically, followed by biologicals or synthetic targeted disease-modifying drugs in refractory courses. Steroids should be avoided in long-term treatment. For optimal transition and further care in adulthood, a close cooperation between internistic and pediatric rheumatologists is necessary.

[Conservative treatment options for arthritis of the ankle : What is possible, what is effective?] / Konservative Optionen zur Therapie der Sprunggelenkarthrose : Was gibt es und was bringt es?

In this article the causes of arthritis in the region of the ankle are introduced and the conservative treatment options are described and discussed more extensively. The risks of treatment with nonopioid analgesics (NOPA) are presented in detail. The topical use of nonsteroidal anti-inflammatory drugs (NSAID) should always be considered in the clinical routine. If contraindications for oral NSAIDs are present, intra-articular treatment is a meaningful option. The best evidence is currently available for viscosupplementation but the study situation for the use of platelet-rich plasma (PRP) is still not sufficiently comprehensive and there are only a few case reports on the use of mesenchymal stem cells..

Characterization of human sulfotransferases catalyzing the formation of p-cresol sulfate and identification of mefenamic acid as a potent metabolism inhibitor and potential therapeutic agent for detoxification.

p-Cresol sulfate, the primary metabolite of p-cresol, is a uremic toxin that has been associated with toxicities and mortalities. The study objectives were to i) characterize the contributions of human sulfotransferases (SULT) catalyzing p-cresol sulfate formation using multiple recombinant SULT enzymes (including the polymorphic variant SULT1A1*2), pooled human liver cytosols, and pooled human kidney cytosols; and ii) determine the potencies and mechanisms of therapeutic inhibitors capable of attenuating the production of p-cresol sulfate. Human recombinant SULT1A1 was the primary enzyme responsible for the formation of p-cresol sulfate (Km = 0.19 ±â€¯0.02 µM [with atypical kinetic behavior at lower substrate concentrations; see text discussion], Vmax = 789.5 ±â€¯101.7 nmol/mg/min, Ksi = 2458.0 ±â€¯332.8 µM, mean ±â€¯standard deviation, n = 3), while SULT1A3, SULT1B1, SULT1E1, and SULT2A1 contributed negligible or minor roles at toxic p-cresol concentrations. Moreover, human recombinant SULT1A1*2 exhibited reduced enzyme activities (Km = 81.5 ±â€¯31.4 µM, Vmax = 230.6 ±â€¯17.7 nmol/mg/min, Ksi = 986.0 ±â€¯434.4 µM) compared to the wild type. The sulfonation of p-cresol was characterized by Michaelis-Menten kinetics in liver cytosols (Km = 14.8 ±â€¯3.4 µM, Vmax = 1.5 ±â€¯0.2 nmol/mg/min) and substrate inhibition in kidney cytosols (Km = 0.29 ±â€¯0.02 µM, Vmax = 0.19 ±â€¯0.05 nmol/mg/min, Ksi = 911.7 ±â€¯278.4 µM). Of the 14 investigated therapeutic inhibitors, mefenamic acid (Ki = 2.4 ±â€¯0.1 nM [liver], Ki = 1.2 ±â€¯0.3 nM [kidney]) was the most potent in reducing the formation of p-cresol sulfate, exhibiting noncompetitive inhibition in human liver cytosols and recombinant SULT1A1, and mixed inhibition in human kidney cytosols. Our novel findings indicated that SULT1A1 contributed an important role in p-cresol sulfonation (hence it can be considered a probe reaction) in liver and kidneys, and mefenamic acid may be utilized as a potential therapeutic agent to attenuate the generation of p-cresol sulfate as an approach to detoxification.

Low-dose aspirin use and risk of head and neck cancer-A Danish nationwide case-control study.

Results concerning a potential preventive effect of aspirin on head and neck cancer (HNC) are conflicting. We examined the association between low-dose aspirin use and HNC risk overall and by degree of human papillomavirus association in a nested case-control study using nationwide registries. Cases (n = 12 389) were all Danish residents diagnosed with primary HNC (2000-2015). Age- and sex-matched population controls (n = 185 835) were selected by risk-set-sampling. Using conditional logistic regression, we estimated multivariable-adjusted odds ratios and 95% confidence intervals for HNC associated with low-dose aspirin use (≥2 prescriptions). No association was observed between low-dose aspirin ever-use and overall HNC (odds ratio: 1.03, 95% confidence interval: 0.97-1.10). Estimates remained neutral according to patterns of use. Low-dose aspirin use appeared to slightly decrease HNC risk among the eldest (71-84 y), independently of human papillomavirus association, while slightly increase HNC risk among younger age groups (30-60, 61-70 y), driven by an increased risk of oral cancer. However, no consistent patterns in risk estimates were found according to duration and consistency of low-dose aspirin use in the age-stratified analyses.

Effect of Nonsteroidal Anti-inflammatory Agents on Small Intestinal Injuries as Evaluated by Capsule Endoscopy.

BACKGROUND: Currently, because the population is aging, use of medications has been increasing, including use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents. AIMS: This study aims to investigate whether NSAIDs can cause damage to the small bowel (SB) mucosa. METHODS: Endoscopic videos of subjects who had undergone capsule endoscopy (CE) were evaluated by three experts in order to identify SB injury. All medications taken within 2 weeks from the time of CE were investigated. Cases with a final diagnosis of intestinal tuberculosis, inflammatory bowel disease, Behcet's disease, Peutz-Jeghers syndrome, small bowel lymphoma, or Henoch-Schönlein purpura were excluded from the analysis. RESULTS: Among the 273 subjects, 125 (45.8%) had SB erosions or ulcers (erosion group) and the remaining 148 (54.2%) did not (no erosion group). SB erosions or ulcers were more common in females, patients aged > 60 years, and subjects taking NSAIDs (p = 0.048, 0.032, and < 0.001, respectively). No statistically significant differences were found between the two groups in the following variables: history of cancer and GI surgery, reasons for the test, comorbidities, and use of anticoagulants and antiplatelet agents. Multivariate analysis showed that use of NSAIDs [OR 4.191 (95% CI 1.858-9.458), p < 0.001] was an independent risk factor for SB erosions or ulcers. CONCLUSIONS: Use of NSAIDs is the only independent risk factor for SB injury identified in this study. Antithrombotic agents do not cause or exacerbate damage to the SB, according to our results. CLINICAL TRIAL REGISTRATION: KCT0004795.

Increased Use of Prophylactic Measures in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs), pancreatic duct stenting, and intensive intravenous hydration have been proven to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Trial participation and guideline changes demanded an assessment of the clinical practice of post-ERCP pancreatitis prophylaxis. AIMS: The surveys aim to identify points of improvement to inform and educate ERCPists about current evidence-based practice. METHODS: Two anonymous surveys were conducted among Dutch gastroenterologists in 2013 (n = 408) and 2020 (n = 575) for longitudinal views and attitudes pertaining to post-ERCP pancreatitis prophylaxis and recognition of post-ERCP pancreatitis risk factors. RESULTS: In 2013 and 2020, respectively, 121 and 109 ERCPists responded. In the 2013 survey, 98% of them utilized NSAID prophylaxis and 62% pancreatic duct stent prophylaxis in specific cases. In the 2020 survey, the use of NSAIDs (100%), pancreatic duct stents (78%), and intensive intravenous hydration (33%) increased among ERCPists. NSAID prophylaxis was the preferred prophylactic measure for all risk factors in the 2020 survey, except for ampullectomy, pancreatic duct contrast injection, and pancreatic duct cannulation, for which NSAID prophylaxis and pancreatic duct stent combined was equally favored or preferred. CONCLUSION: Rectal NSAIDs are the most applied post-ERCP pancreatitis prophylaxis in the Netherlands, followed by pancreatic duct stents and intensive intravenous hydration. Additionally, there is reason to believe that recent guideline updates and active research participation have led to increased prophylaxis implementation.

Use of nonaspirin nonsteroidal anti-inflammatory drugs and risk of head and neck cancer: A nationwide case-control study.

Head and neck cancer (HNC) is the sixth most frequent malignancy with high mortality and substantial morbidity and hence there is a need for identification of preventive factors. Preclinical and observational studies have reported antineoplastic effects of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), but studies of nonaspirin NSAID use and risk of HNC are sparse and with inconsistent results. We therefore conducted a register-based case-control study nested in the entire Danish population. Cases (n = 12,389) comprised all Danish residents aged 30-84 years with a histologically verified primary HNC diagnosis during 2000-2015. Based on the literature, cases were categorized into four groups of anticipated association with human papillomavirus (HPV): strong, potential, no/weak and uncertain. Age- and sex-matched population controls (n = 185,835) were selected by risk-set-sampling. We obtained information on filled prescriptions of nonaspirin NSAIDs, other drug use, comorbid conditions and socioeconomic parameters from nationwide Danish registries. Ever-use (≥2 prescriptions) of nonaspirin NSAIDs was not associated with the overall risk of HNC after adjustment for potential confounders (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.95-1.03). However, long-term consistent use (≥5 years) was associated with a 25% reduction in HNC risk (OR: 0.75, 95% CI: 0.62-0.90). Stratified analyses by anticipated HPV-association showed no material differences in estimates. In conclusion, ever-use of nonaspirin NSAIDs was not associated with the risk of HNC with no apparent influence on the estimates by the anticipated HPV-association. However, long-term consistent use may be associated with a reduced risk of HNC and merits further investigation.

Nonsteroidal anti-inflammatory drug use and breast cancer risk in a European prospective cohort study.

Experimental studies have shown a protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer development. However, results from epidemiological cohort studies are less consistent. Our objective was to assess the association between NSAID use and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self-reported information on NSAID use at baseline has been collected in five EPIC countries. Multivariable Cox regression models were used to estimate hazard ratios for the association of NSAID use with breast cancer incidence with adjustment for potential confounders. We also assessed effect modification by breast cancer risk factors and examined the associations within specific breast cancer subtypes. Among the 140,981 women included in the analysis, 7% were regularly using NSAIDs at baseline. During a median follow-up time period of 13 years, 7,379 incident breast cancer cases were diagnosed (816 in situ and 6,563 invasive). There were no statistically significant associations between NSAID use and breast cancer risk, overall and by subtypes. However, a statistically significant interaction was observed for invasive cases between NSAID use and ever use of menopausal hormonal therapy (MHT) among postmenopausal women [MHT users: HRNSAID use = 0.84 (0.73-0.96); non MHT users: HRNSAID use = 1.08 (0.93-1.25); pinteraction = 0.05]. Our results indicate potential effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in-depth investigation in studies with accurate data on both NSAID and MHT use.

Analgesic effectiveness, pharmacokinetics, and safety of a paracetamol/ibuprofen fixed-dose combination in children undergoing adenotonsillectomy: A randomized, single-blind, parallel group trial.

BACKGROUND: Pain following tonsillectomy is often poorly managed in the home setting. Multimodal analgesia with acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs offers superior analgesia over monotherapy but may be difficult for caregivers to manage. A fixed-dose combination oral suspension product containing paracetamol and ibuprofen has been developed to facilitate pediatric dosing. AIMS: The aims of this study are to determine the analgesic effectiveness, pharmacokinetics, and safety of the fixed-dose combination at two doses in the pediatric population. METHODS: In this prospective, multicenter, randomized, single-blind, parallel group trial, 251 children aged 2-12 years undergoing day-stay (adeno)tonsillectomy were randomized to two dose groups of the fixed-dose combination. A doubled loading dose was given preoperatively, followed by treatment for up to 11 days (Higher dose: paracetamol 15 mg/kg + ibuprofen 4.5 mg/kg, Lower dose: paracetamol 12 mg/kg + ibuprofen 3.6 mg/kg). Blood samples were collected for pharmacokinetic analysis for up to 6 hours after the loading dose. The analgesic effectiveness was examined on the first day after surgery using both Parents Postoperative Pain Measurement and modified Wong-Baker Faces pain scales. Rescue medication consumption was recorded throughout the study. RESULTS: Differences in maximum plasma concentration (Cmax ) and total exposure (AUC0→t ) between the treatment groups for both analytes were consistent with a 25% increase in dose; there was no difference in time to peak concentration (Tmax ). On the first postoperative day, there was no difference in pain scores or rescue medication use between treatment groups (approximately 30% in both groups). The combination was well tolerated by both groups. The most common adverse events were vomiting and nausea. The incidence of postoperative bleeding was 4.4%. CONCLUSION: The shallow dose-response relationship and good tolerability of the fixed-dose combination over an extended study period supports the utility of both doses of the fixed-dose combination in the home setting.

Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors.

OBJECTIVE: To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians. DATA SOURCES: A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs. Reference lists of included articles were reviewed to find additional eligible articles. STUDY SELECTION AND DATA EXTRACTION: All English-language observational, randomized, and pharmacokinetic (PK) studies assessing LD-MTX interactions in humans were analyzed to determine clinical relevance in making recommendations to clinicians. Clinical case reports were assigned a Drug Interaction Probability Scale score. DATA SYNTHESIS: A total of 32 articles were included (28 with NSAIDs, 3 with penicillins, and 2 with PPIs [1 including both PPI and NSAID]). Although there are some PK data to describe increased LD-MTX concentrations when NSAIDs are used concomitantly, the clinical relevance remains unclear. Based on the limited data on LD-MTX with penicillins and PPIs, no clinically meaningful interaction was identified. CONCLUSION: Given the available evidence, the clinical importance of the interaction between LD-MTX and NSAIDs, penicillins, and PPIs cannot be substantiated. Health care providers should assess the benefit and risk of LD-MTX regardless of concomitant drug use, including factors known to predispose patients to MTX toxicity, and continue to monitor clinical and laboratory parameters per guideline recommendations.

Management of Chronic Spontaneous Urticaria in Routine Clinical Practice Following the EAACI/GA(2)LEN/EDF/WAO Guidelines. / Manejo de la urticaria crónica espontánea en la práctica clínica diaria siguiendo las indicaciones de la guía EAACI/GA(2)LEN/EDF/WAO.

INTRODUCTION: Chronic spontaneous urticaria is a prevalent and difficult-to-treat condition that has a very negative impact on patient quality of life. OBJECTIVE: To describe the epidemiological and clinical characteristics of patients presenting with chronic spontaneous urticaria and the response to treatment administered according to the EAACI/GA(2)LEN/EDF/WAO consensus guideline. MATERIAL AND METHOD: Descriptive cross-sectional study of all the patients with chronic spontaneous urticaria who consulted a skin allergy unit in the dermatology department of a tertiary hospital in Spain between July 2011 and July 2015. RESULTS: The study included 100 patients with chronic spontaneous urticaria; inducible urticaria was present in 43% of cases, and angioedema in 40%. On diagnosis, 53% of patients were taking nonsteroidal anti-inflammatory drugs. All patients were treated with second generation H1-antihistamines, but the standard dose was sufficient in only 18% of cases. Higher doses (up to 4 times the standard dose) achieved control of the urticaria in 74% of the patients studied. Higher doses of second generation H1-antihistamines were required to control the condition in patients with angioedema, and the presence of angioedema was associated with a lack of response to treatment with these drugs (OR, 6.1%; P<.001). One in 4 patients failed to respond to second generation H1-antihistamines and required treatment with omalizumab or ciclosporin to control their condition. CONCLUSIONS: Doses of H1-antihistamines higher than the standard dose are required in most cases to achieve control of chronic spontaneous urticaria. Angioedema is associated with failure to respond to treatment with antihistamines. In refractory cases, control of the condition can be achieved with omalizumab or ciclosporin. Patients with chronic spontaneous urticaria do not generally avoid the use of nonsteroidal anti-inflammatory agents.

Analgesic use and the risk of primary adult brain tumor.

Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma.

Safely Managing Acute Osteoarthritis in the Emergency Department: An Evidence-Based Review.

BACKGROUND: Joint pain caused by acute osteoarthritis (OA) is a common finding in the emergency department. Patients with OA often have debilitating pain that limits their function and ability to complete their activities of daily living. In addition, OA has been associated with a high percentage of arthritis-related hospital admissions and an increased risk of all-cause mortality. Safely managing OA symptoms in these patients can present many challenges to the emergency provider. OBJECTIVES: We review the risks and benefits of available treatment options for acute OA-related pain in the emergency department. In addition, evidence-based recommendations will be made for safely managing pain and disability associated with OA in patients with comorbidities, including cardiovascular disease, renal insufficiency, and risk factors for gastrointestinal bleeding. DISCUSSION: Commonly used treatments for OA include acetaminophen, oral nonsteroidal anti-inflammatory drugs, and opioids, each with varying degrees of efficacy and risk depending on the patient's underlying comorbidities. Effective alternative therapies, such as topical preparations, intra-articular corticosteroid injections, bracing, and rehabilitation are likely underused in this setting. CONCLUSIONS: Emergency providers should be aware of the risks and benefits of all treatment options available for acute OA pain, including oral medications, topical preparations, corticosteroid injections, bracing, and physical therapy.

Toll-like receptor (TLR) 2 agonists ameliorate indomethacin-induced murine ileitis by suppressing the TLR4 signaling.

BACKGROUND AND AIM: Few drugs have been found satisfactory in the treatment of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy. Toll-like receptor (TLR) 4 and aberrant leukocyte migration to the intestinal mucosa are reported to be involved in the pathology of intestinal enteropathy and TLR2 agonists have been found to evoke hyposensitivity to TLR4 stimulation in vitro. In this study, we investigated whether and how lipoarabinomannan (LAM) or lipoteichoic acid (LTA), TLR2 agonists, attenuated indomethacin (IND)-induced intestinal damage. METHODS: LAM (0.5 mg/kg) or LTA (15 mg/kg) was administered intraperitoneally to mice before IND (10 mg/kg) administration. Disease activity was evaluated macroscopically and histologically. In the migration analysis, fluorescence-labeled leukocyte movement in the intestinal microvessels was observed by intravital microscopy. Expression of P-selectin, MAdCAM-1, TLR2, TLR4, and F4/80 was observed immunohistochemically. In the in vitro analysis, RAW264.7 macrophage cells were preincubated with LAM and stimulated with lipopolysaccharide (LPS), and the mRNA expression levels of TLR4, tumor necrosis factor-α, and interleukin-12p40 were measured. RESULTS: Pretreatment with LAM or LTA significantly decreased IND-induced injury as well as decreased leukocyte infiltration. Pretreatment with LAM decreased IND-induced TLR4 expression on F4/80(+) macrophages, the level of P-selectin expression, and leukocyte migration in the small intestinal vessels. In the in vitro study, a single administration of LAM decreased TLR4 mRNA expression and inhibited the increase in mRNA expression of inflammatory cytokines by LPS in a dose-dependent manner. CONCLUSION: TLR2 agonists attenuated IND-induced small intestinal lesions and leukocyte infiltration probably by suppressing the TLR4 signaling pathway in tissue macrophages.

Safety risks for patients with aspirin-exacerbated respiratory disease after acute exposure to selective nonsteroidal anti-inflammatory drugs and COX-2 inhibitors: Meta-analysis of controlled clinical trials.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause bronchospasm in susceptible patients with asthma, often termed aspirin-exacerbated respiratory disease (AERD), with the risk being greatest after acute exposure. Selective NSAIDs that preferentially inhibit COX-2 might be safer. OBJECTIVE: We sought to systematically evaluate changes in symptoms and pulmonary function after acute selective NSAID or COX-2 inhibitor exposure in patients with the AERD phenotype. METHODS: A systematic review of databases was performed to identify all blinded, placebo-controlled clinical trials evaluating acute selective NSAID or COX-2 inhibitor exposure in patients with AERD. Effect estimates for changes in respiratory function and symptoms were pooled by using fixed-effects meta-analysis, with heterogeneity investigated. RESULTS: No significant difference in respiratory symptoms (risk difference, -0.01; 95% CI, -0.03 to 0.01; P = .57), decrease in FEV1 of 20% or greater (RD, 0.00; 95% CI, -0.02 to 0.02; P = .77), or nasal symptoms (RD, -0.01; 95% CI, -0.04 to 0.02; P = .42) occurred with COX-2 inhibitors (eg, celecoxib). Selective NSAID exposure caused respiratory symptoms in approximately 1 in 13 patients with AERD (RD, 0.08; 95% CI, 0.02 to 0.14; P = .01). No significant differences were found according to leukotriene antagonist exposure or whether NSAIDs were randomly allocated. CONCLUSION: According to clinical trial evidence in patients with stable mild-to-moderate asthma with AERD, acute exposure to COX-2 inhibitors is safe, and selective NSAIDs exhibit a small risk. Thus COX-2 inhibitors could be used in patients with AERD or in patients with general asthma unwilling to risk nonselective NSAID exposure when oral challenge tests are unavailable.

Comparison of NSAID patch given as monotherapy and NSAID patch in combination with transcutaneous electric nerve stimulation, a heating pad, or topical capsaicin in the treatment of patients with myofascial pain syndrome of the upper trapezius: a pilot study.

OBJECTIVE: This study compared the therapeutic effect of monotherapy with a nonsteroidal anti-inflammatory drug (NSAID) patch vs an NSAID patch combined with transcutaneous electric nerve stimulation (TENS), a heating pad, or topical capsaicin in the treatment of patients with myofascial pain syndrome (MPS) of the upper trapezius. DESIGN: A randomized, single-blind, controlled study of combination therapy for patients with MPS was performed. METHODS: Ninety-nine patients were randomly assigned to one of four different self-management methods for treatment: NSAID patch (N = 25), NSAID patch + TENS (N = 24), NSAID patch + heating pad (N = 25), and NSAID patch + topical capsaicin (N = 25). The NSAID patch used in this study was a ketoprofen patch. All treatment groups were observed for 2 weeks, and the numeric rating scale (NRS) pain score, cervical active range of motion, pressure pain threshold, and Neck Disability Index were assessed. RESULTS: There was no significant difference between the NSAID patch alone group and the three combination therapy groups with respect to decrease in NRS score from baseline (day 0) to each period of observation. In covariate analysis, although there was no difference among the groups in most of the periods, the data at day 14 indicated a trend (P = 0.057). There were no significant differences in the other variables. CONCLUSIONS: We did not observe a statistical difference in improvements to the clinical variables among the four different methods. However, further studies regarding the effectiveness of a mixture of topical capsaicin and ketoprofen in patients with MPS should be considered.

Evaluation of Postoperative Efficacy and Safety of Celecoxib in Children Hospitalized After Adenotonsillectomy.

OBJECTIVE: The choice of optimal analgesia following an adenotonsillectomy is a clinical issue because of the risk of respiratory depression and bleeding. The objective of this study was to assess the effect of celecoxib on opioid use and pain scores in children hospitalized after adenotonsillectomy and to document its adverse effects. METHODS: This retrospective study was conducted in a tertiary care pediatric hospital. We compared a group of subjects aged 1 to 17 years who were prescribed celecoxib and opioids between January 2017 and June 2020 following an adenotonsillectomy during a 3-day or less hospitalization to a group of matched controls for sex, age, and length of stay who were prescribed opioids. RESULTS: A total of 228 patients were identified (76 in the celecoxib + opioids group, 152 in the control group). Opioid use, in oral morphine equivalent daily dose, was lower in the celecoxib + opioids group at 0 to 24 hours of hospitalization (0.15 vs 0.20 mg/kg/day, p = 0.05). Initiating celecoxib within 24 hours of surgery (n = 60) significantly reduced opioid requirement for up to 48 hours compared with controls (0-24 hours: 0.12 vs 0.20 mg/kg/day, p = 0.002; 25-48 hours: 0.02 vs 0.09 mg/kg/day, p = 0.001). A shorter length of stay was observed for patients receiving celecoxib + opioids during the first 24-hour post--operative period (27 vs 32 hours, p = 0.01). With celecoxib use, no significant change in pain scores and occurrence of adverse effects including bleeding was found. CONCLUSIONS: Using celecoxib early after an adenotonsillectomy has reduced both opioid use and duration of hospital stay without increasing adverse effects or bleeding.

[Diagnostics of drug allergies and intolerances]. / Diagnostik von Arzneimittelallergien und -intoleranzen bei Kindern und Jugendlichen.

The prevalence of hypersensitivity reactions to drugs is increasing. Currently, this affects more than 7% of the world population. Nonsteroidal anti-inflammatory drugs (NSAID) and beta-lactam antibiotics (BLA) are by far the most common pharmaceutical preparations involved in hypersensitivity reactions to drugs. Misdiagnoses are frequent and BLA allergies present a danger that can lead to adverse health outcomes. Therefore, delabeling (exclusion of a suspected diagnosis) is paramount for those affected. Following the occurrence of uncomplicated maculopapular exanthemas, outpatient oral drug provocation can be safely considered in children without prior skin tests. Immediate perioperative reactions are rare. The approach to studying these complex reactions requires collaboration between allergologists and anesthesiologists to provide the best possible care for these patients.

Acupressure versus NSAID for relief of orthodontic pain : A randomized controlled clinical trial.

AIM: To compare ibuprofen and acupressure for pain relief after insertion of elastomeric orthodontic separators. MATERIALS AND METHODS: A randomized control clinical trial was conducted in an orthodontic clinic. A total of 75 orthodontic patients aged 12-16 years participating in the study were randomly allocated to receive either 400 mg of oral ibuprofen, applying acupressure therapy, or no pain-relief approach. Pain scores were recorded on visual analog scales (10 cm) over a week at different times (4, 10, 18, 24 h, and 1 week). The margin of equivalence was defined as 10 mm. RESULTS: For all timepoints, the control group recorded the highest pain. For the ibuprofen and acupressure group, after 4 h, 18 h, and 1 week, no significant difference was noted. However, after 10 h, no significant difference in pain between the control and acupressure groups was noted and the ibuprofen group showed significantly lower pain. In the acupressure group, the highest pain was noted at 10 h. After this timepoint, pain progressively decreased with time and the lowest pain was noted after 1 week. In the control and ibuprofen groups, the highest pain was after 4 h, and then progressively decreased with time and the lowest pain was noted after 1 week. CONCLUSIONS: There was no significant difference in pain perception between participants using ibuprofen or acupressure and both groups recorded significantly lower pain than the control group at most of the observed timepoints. Results support the analgesic effect of the acupressure approach.