Intake Of Non-steroidal Anti-inflammatory Drugs Research Articles

Peptic ulcer disease and H. pylori gastritis: key advances in clinical management

Helicobacter pylori (H. pylori) gastritis and non-steroidal anti-inflammatory drug (NSAID) intake are the most important risk factors for peptic ulcer disease (PUD) and ulcer bleeding. H. pylori infection was shown to increase the risk of ulcer bleeding in patients with PUD who are taking NSAID, aspirin, or another antiplatelet drug. H. pylori-positive patients on combined platelet aggregation inhibition are at the highest risk of bleeding. Evidence-based interdisciplinary treatment recommendations for the safe use of NSAID have been released. For patients with a moderate risk of PUD, the combination of NSAID and a proton pump inhibitor (PPI) or a monotherapy with a selective cyclooxygenase-2 (COX-2) inhibitor is recommended, whereas patients with a high risk of bleeding should receive a combination of a selective COX-2 inhibitor and a PPI. According to a recent randomized trial, hemodynamically stable patients with signs of upper gastrointestinal bleeding and an increased risk of death (Glasgow-Blatchford Score ≥ 12) undergoing endoscopy 6-24 after consultation do not have any disadvantage in terms of 30-day mortality compared to patients receiving endoscopy within 6 hours. After successful endoscopic hemostasis, additional prophylactic angiographic embolization does not reduce the risk of recurrent bleeding. Successful H. pylori eradication reduces the risk of developing gastric cancer (GC) in first-degree relatives of patients with GC by 73 %. In patients with successful endoscopic treatment of early GC, H. pylori testing with subsequent eradication also halves the rate of metachronous GC. Clarithromycin-based triple therapy for H. pylori eradication shows a decreasing effectiveness due to increasing antibiotic resistance, especially against macrolides. Accordingly, bismuth-containing quadruple therapy is widely recommended as the standard empiric first-line therapy.

Management of patients with subacute back pain: how to effectively prevent chronicity

A clinical observation of a patient with subacute nonspecific lower back pain and comorbid panic disorder is presented; it illustrates a modern approach to the management of this type of patients. Subacute back pain is the transition from acute to chronic pain. Clinically, the pain becomes constant, exhausting the patient and reducing his quality of life, and pathophysiologically, the pain transforms from nociceptive to dysfunctional. Chronicity of musculoskeletal pain does not occur in conditions of mental and social well-being, the patient necessarily has the so-called “yellow flags” – factors that contribute to central sensitization and chronic pain. In the presented clinical case, the most common “yellow flags” were identified – anxiety, misunderstanding about the causes of back pain, pain catastrophizing, restrictive “pain” behavior. These factors are often found among patients with subacute back pain. It is important to identify “yellow flags” timely and treat patient taking into account their correction. For the treatment of this category of patients, the prescription of pain therapy alone is not enough, an interdisciplinary approach is needed, which will include rational pharmacotherapy, psychological methods and kinesiotherapy. The patient underwent interdisciplinary treatment, including non-drug and drug therapies and in accordance with Russian and foreign clinical guidelines for the treatment of subacute nonspecific lower back pain and panic disorder. Non-drug treatment consisted of educational talks, recommendations for daily activities, cognitive behavioral therapy, and kinesiotherapy. These methods were aimed at forming the patient's correct ideas about his condition, at reducing the catastrophizing of pain and anxiety, and at increasing the patient's physical and social activity. It is known that many patients with pain syndromes have insufficient adherence to treatment and adherence to medical recommendations. Patient adherence to non-drug treatments was maintained through educational conversations and cognitive-behavioral therapy. Taking into account the previous multiple intake of non-steroidal anti-inflammatory drugs and in order to avoid the risk of side effects, drugs of this group were not included in the present pharmacotherapy plan. The patient was prescribed Alflutop as a pharmacotherapy. After 10 days of treatment, a marked relief of pain was observed, and after 3 weeks of treatment, back pain regressed, and anxiety significantly decreased. The patient has formed correct ideas about his condition, about his lifestyle. Follow-up of the patient for 12 months showed that there were no repeated episodes of back pain and panic attacks. The patient continued to regularly engage in kinesiotherapy and maintain an active lifestyle.

Association of ATP8B3 gene polymorphisms with aspirin-exacerbated respiratory disease in asthmatics.

Aspirin-exacerbated respiratory disease (AERD), an asthma phenotype, often presents with severe manifestations and it remains widely underdiagnosed because of insufficient awareness of the relationship between the ingestion of nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid (ASA), and asthma exacerbation. Our previous genome-wide association study demonstrated an association between a single nucleotide polymorphism (SNP) of the ATP8B3 gene and the risk of AERD. This study examined AERD-related SNPs of the ATP8B3 gene in a large population. Twenty-five SNPs of ATP8B3 were genotyped with the GoldenGate assay using VeraCode microbeads in 141 asthmatics with AERD and 995 Aspirin-tolerant asthma (ATA). The genotype distribution was analyzed using logistic regression models. The declines in forced expiratory volume in 1 second (FEV1)following an ASA challenge were compared among the genotypes and haplotypes using a type III generalized linear model. The minor allele frequencies (MAFs) of rs10421558 A>G in the 5'UTR and rs10403288 G>A in the intron were significantly lower in the AERD than the ATA [34.0% vs. 43.8%, OR = 0.66 (0.62-0.92), Pcorr = 0.03 and 28.4% vs. 35.4%, OR = 0.62 (0.59-0.89), Pcorr = 0.016, respectively]. BL1ht5 was significantly higher in the AERD [7.6% vs. 1.6%, OR = 12.23 (0.2-0.51), P = 4.7 × 10 -4 , Pcorr = 0.001]. Among them, rs10421558 A>G and BL1ht5 were associated with the percent decline in FEV1 on the oral ASA challenge test. The minor allele of rs10421558 A>G in the 5'UTR may protect against the development of AERD via the increased production of ATP8B3.

Treatment With Tumor Necrosis Factor Inhibitors Is Associated With a Time-Shifted Retardation of Radiographic Sacroiliitis Progression in Patients With Axial Spondyloarthritis: 10-Year Results From the German Spondyloarthritis Inception Cohort.

To investigate the longitudinal association between radiographic sacroiliitis progression and treatment with tumor necrosis factor inhibitors (TNFi) in patients with early axial spondyloarthritis (SpA) in a long-term inception cohort. We included patients from the German Spondyloarthritis Inception Cohort who underwent radiographic assessment of the sacroiliac joints at baseline and at least once more during the 10-year follow-up. Two central readers scored the radiographs according to the modified New York criteria for ankylosing spondylitis. The sacroiliac sum score was calculated as a mean of the scores determined by both readers. TNFi use was assessed according to exposure in the current and/or previous 2-year radiographic interval. The association between TNFi use and radiographic sacroiliitis progression was examined by longitudinal generalized estimating equation analysis with adjustment for potential confounders. In this long-term inception cohort, 10-year follow-up data on 737 radiographic intervals assessed in 301 patients with axial SpA (166 patients with nonradiographic axial SpA and 135 patients with radiographic axial SpA) were obtained. Having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was associated with a significant decrease in the sacroiliitis sum score (β=-0.09 [95% confidence interval (95% CI) -0.18, -0.003]; analyses adjusted for age, sex, symptom duration, HLA-B27 status, Bath Ankylosing Spondylitis Disease Activity Index score, C-reactive protein, and nonsteroidal antiinflammatory drug intake). In contrast, among patients receiving TNFi in the current radiographic interval, there was no significant association with change in the sacroiliitis sum score (β=0.05 [95% CI -0.05, 0.14]). This effect of having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was stronger in patients with nonradiographic axial SpA as compared to patients with radiographic axial SpA (β=-0.16 [95% CI -0.28, -0.03] versus β=-0.04 [95% CI -0.15, 0.07]). Treatment with TNFi was associated with the reduction in radiographic sacroiliitis progression in patients with axial SpA. This effect became evident between 2 and 4 years after treatment was initiated.

MO43-1 Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) and associated risk of Barrett's esophagus: A systematic review

Barrett's esophagus (BE) is a condition characterized by conversion of normal squamous epithelium into metaplastic columnar epithelium. Individuals with BE are predisposed to esophageal adenocarcinoma, a cancer with high morbidity and mortality. Aspirin and other NSAIDs have been suggested to protect against esophageal adenocarcinoma. The aim of this study is to evaluate the risk of developing Barrett's esophagus with aspirin or other NSAIDs intake.

Treatment with tumour necrosis factor inhibitors is associated with a time-shifted retardation of radiographic spinal progression in patients with axial spondyloarthritis

ObjectiveThe objective of the current study was to analyse the association between treatment with tumour necrosis factor inhibitors (TNFi) and radiographic spinal progression in patients with axial spondyloarthritis (axSpA) from...

The Effect of Diclofenac Sodium on Callus Formation in White Male Rat (Rattus norvegicus) Cruris Fracture Healing

Highlights: Sodium diclofenac is one of NSAID a common treatment to relieve pain associated with bone fractures. Sodium diclofenac with a some dose of body weight could decrease the callus quality on fracture healing. Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac sodium, are standard treatments to relieve pain associated with bone fractures. The bone healing process consists of four stages: inflammation, soft callus formation, complex callus formation, and bone remodeling. Previous studies mentioned that intake of NSAIDs (sodium diclofenac) could inhibit the bone healing process. This study examined the effect of diclofenac sodium intake on callus formation in fracture healing. In this study, thirty-six rats (Rattus Norvegicus) with fractures were used and divided into two groups, namely 18 rats for the control and 18 rats for the treatment group. In the treatment group, each rat was given 1.8 mg sodium diclofenac/150 grams of body weight per day. In the control group, each rat was given CMC-Na 0.5% with equal volume as diclofenac sodium in the treatment group. After 28 days, all the rats were stunned until dead, and the diameter and strength of their calluses were measured. In the treatment group with diclofenac sodium1.8 mg/ 150 grams BW/ 28 days after the tibia bone callus was pressed using the Shimadzu tool, the lowest callus strength was found to be 56.500 N, and the highest callus strength was 59.000 N. The lowest callus diameter in the treatment group was 4 mm, the highest was 5 mm. In the control group, the lowest callus strength was 76 N, and the highest callus strength was 77 N. The lowest callus diameter in the control group was 6 mm, and the highest was 8 mm. The strongest callus in the treatment group was found in the sixth observation, with a value of 59 N and a diameter of 4 mm. In the control group, the highest callus strength was 77 N, with a diameter of 7-8 mm. These measurements were found on the 5th, 7th, 8th, 9th, 16th, and 17th observations. Diclofenac sodium with a dose of 1.8 mg/150 grams of body weight could decrease the callus quality parameters, such as callus strength and diameter on fracture healing.

A review of risk factors and prevention strategies for exercise associated hyponatremia.

Exercise-associated hyponatremia (EAH) is defined as a serum sodium concentration under 135mmol·L-1 during or within 24h of exercise. Increasing interest in endurance events has led to a higher number of athletes presenting with this potentially life-threatening condition. EAH is largely caused by the overconsumption of hypotonic fluids leading to weight gain during exercise. The primary risk factors include the inappropriate secretion of arginine vasopressin, longer exercise duration, smaller body mass, and to smaller extent ingestion of non-steroidal anti-inflammatory drugs. Accurate tracking of fluid intake and losses to prevent weight gain during exercise, sodium supplementation, and heat acclimatization may help attenuate declines in serum sodium concentration during exercise.

Prescripción potencialmente inadecuada: utilidad de los criterios STOPP/START versión 2 a nivel poblacional en Cataluña

ObjectiveTo measure the prevalence of potentially inappropriate prescribing (PIP) among the elderly population in Catalonia using criteria Screening Tool of Older Person's Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) version 2. In addition, to evaluate the association between PIP and several factors (polypharmacy, gender, age and sociodemographic conditions). Materials and methodsDesign: Retrospective cross sectional population study. SettingsPrimary Health Care, Catalonia, Spain. ParticipantsThe study population comprised of participants 70 years old and over, who attended primary health care centres in Catalonia in 2014 (700.058 patients). Main analysis55 STOPP and 19 START criteria are applied to analyse PIP prevalence. Logistic regression models are adjusted to determine PIP association with several factors. ResultsThe mean age is 79. 2±6.5. 58.5% being female. 38.7% of patients have 7 or more prescribed drugs, whereas 50% go to a primary care centre 10 or more times during one year. The most frequent PIP among STOPP criteria are related to nonsteroidal anti-inflammatory drug intake, antiplatelet and anticoagulants use, and benzodiazepines.According to START, the most frequent omissions are vitamin D and calcium supplements, antidepressants, and cardiovascular medications.Factors that increase PIP are: female gender, living in a nursing home, receiving home health care, polypharmacy and frequent visits to primary care centres. ConclusionsThe overall prevalence of PIP is 89.6%. PPI is significantly related to certain drugs and patient's conditions. The knowledge of this association is important for the implementation of security measures for medical prescription.

POS-548 GLOMERULAR FILTRATION STATE OF CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS ACCORDING TO Cys-C INDICATORS

According to modern literature reveiw, it is believed that about 8% of children with juvenile idiopathic arthritis (JIA) have chronic kidney disease. Subclinical kidney damage in JIA remains undiagnosed in real clinical practice. Kidney damage can manifest itself as a complication of the underlying disease or, as a consequence, its long-term treatment.The structure of renal pathology in JIA is represented by secondary amyloidosis, glomerulonephritis, tubulo-interstitial nephritis. We investigated the level of cystatin C (Cys-C) in the blood of 80 children with JIA. The age of the subjects was from 3 to 17 years. The calculation of the glomerular filtration rate (GFR) was carried out twice (the first and third months of the study) on the basis of the concentration of Cys-C and creatinine in serum according to the methods: Hoek F.J. et al. (2003), Equation based on cystatin C (2012), Schwartz and Counahan-Barratt (2012). Cys-C averaged 0.886 ± 0.1495 (0.84; 0.79-0.98) μg / ml. The average GFR according to the 2012 equation based on cystatin C was 81.04 ± 12.129 (82.92; 71.74-88.53) ml / min / 1.73 m2, which is significantly lower than with the same GFR calculated using the method Hook - 88.81 ± 14.948 (91.05; 77.32- 98) ml / min / 1.73 m2, p <0.01. The percentage below normal GFR calculated using the 2012 equation based on cystatin C was twice that calculated using Hook's formula: 65 (81.3%) versus 33 (41.3%) cases (p <0.001 according to McNemar's test ). Analysis of the frequency of GFR decline, calculated on the basis of creatinine and Cys-C, also revealed a number of significant differences. Thus, the cystatin C-based equation technique compared with Schwartz and Counahan-Barratt 2012 methods overestimated the incidence of GFR abnormalities by 81.3% (p <0.001) and 47.5% (p <0.001), respectively, in the first month of the study and 81 respectively 3% (p <0.001) and 55.0% (p <0.001) in the third month. A similar comparison with Hook's method showed that according to the Schwartz formula, GFR decreased by 41.3% less often (p <0.001) both in the first and in the third month. The Counahan-Barratt formula did not show significant differences in the first study of creatinine (difference 7.5%, p <0.05), and the second study showed that the decrease in GFR according to the Counahan-Barratt was recorded 15.0% less frequently than according to the data on Hook's method - a deviation close to the level of significance, p <0.09. A more subtle method for detecting subclinical kidney damage in children with JIA is to determine the level of cystatin C followed by calculating the glomerular filtration rate, according to Hook's formula. The concentration of Cys-C was directly related to the duration of the use of non-steroidal drugs (ρ = 0.44, p <0.04), thus, the lengthening of their use had a negative effect on GFR (ρ = -0.44, p <0.04) . And, conversely, with an increase in the duration of immunobiological therapy, the level of cystatin C in the blood decreased (ρ = -0.48, p <0.02) and GFR increased (ρ = 0.48, p <0.02). When detecting a decrease in GFR in children with JIA, it is necessary to limit the intake of non-steroidal anti-inflammatory drugs and increase the basic therapy.

Simultaneous quantification of 19 nonsteroidal anti-inflammatory drugs in oral fluid by liquid chromatography-high resolution mass spectrometry: Application on ultratrail runner's oral fluid.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a therapeutic class suspected to be used by ultratrail runners. The use of NSAIDs during ultratrails is known to be associated with various adverse effects. To study the prevalence of NSAIDs intake in ultratrail runners, oral fluid (OF) is a relevant matrix as it is noninvasive and easy to collect. The aim of our work was to develop and validate a liquid-liquid extraction followed by a liquid chromatography (LC)-mass spectrometry (MS)/high resolution mass spectrometry (HRMS) method for the simultaneous quantification of 19 NSAIDs in OF. After a comparison of different liquid-liquid extraction methods, a double step liquid-liquid extraction with chloroform was performed on OF collected with Quantisal®, with extraction recoveries higher than 90%. An Accucore AQ column was selected for the chromatographic separation of NSAIDs. The Q Exactive Plus mass spectrometer operated in full scan and ddms2 mode after positive and negative electrospray ionization. Selectivity, carry-over, matrix effect, and linearity were validated for all NSAIDs. Within-day and between-day accuracy and precision were validated for all NSAIDs (<15% for quality control [QC] samples and <20% for lower limit of quantitation [LLOQ]), except within-day accuracy for the LLOQ of mefenamic acid. A stability study was also performed on OF at room temperature and +4°C. The method was applied on OF from runners who participate to Ultra Trail du Mont Blanc®.

Meloxicam clinical effects

Pain syndromes, acute and chronic, against the background of inflammatory diseases (such as osteoarthritis (OA)), degenerative-dystrophic changes (involutive process, trauma) or systemic diseases (rheumatoid arthritis, etc.) dictate a steady increase in the intake of nonsteroidal anti-inflammatory drugs (NSAIDs). The choice of the most «safe NSAID» is based on the assessment of the toxicity index (the ratio when blocking cyclooxygenase (COX)) and the development of relative risks (the benefit/risk ratio). As well as those adverse events that can be detected with individual sensitivity to a specific NSAIDs, taking into account the anamnesis of previous diseases and intolerance to NSAIDs, existing chronic diseases (gastrointestinal tract, cardiovascular system, type 2 diabetes mellitus), limiting the appointment of NSAIDs. Considering these circumstances, the NSAID meloxicam (Amelotex) can be recommended for the treatment of various genesis pain syndromes. A number of studies have demonstrated the efficacy and safety of meloxicam with different methods of its administration (per oral (p/o), intramuscularly (i/m)) in the treatment of pain syndrome in the lower back, with OA, etc. Recent studies concern intravenous (i/v) meloxicam (30 mg) administration with moderate and severe postoperative pain syndrome. Today, the most commonly pain therapy scheme using meloxicam includes step-by-step administration of injectable and oral forms: meloxicam i/m (1.5 ml) for 3-5 days, followed by a transition to p/o (7.5-15 mg) intake for 14 days, or complex therapy with meloxicam (Amelotex), with muscle relaxant and B vitamins.

Uninvestigated Dyspepsia and Heartburn Overlap Syndrome at Industrial Hub of Eastern Siberia

Aim. A study of the overlap syndrome of uninvestigated dyspepsia and heartburn at an industrial hub city of Eastern Siberia.Materials and methods. A total of 1,382 subjects (684 men and 698 women, mean age 40.6 years) were randomly selected and examined for the central district of Krasnoyarsk. The clinical check-up and interviewing results were registered with a standard questionnaire. Heartburn was diagnosed as per the Montreal Consensus. Since no endoscopic patient examination had been performed, dyspepsia was assumed uninvestigated. Dyspepsia was diagnosed as per the Rome IV criteria. The study conduction complied with ethical standards. Each participant signed an informed examination consent, in accordance to the regulations by the World Medical Association’s Declaration of Helsinki. The survey data were analysed with common statistical methods.Results. Heartburn, uninvestigated dyspepsia and their overlap syndrome had prevalence of 12.4, 21.1 and 5% in study population, respectively. Uninvestigated dyspepsia was registered in 40.4% patients with and 18.4% — without heartburn (p &lt; 0.001). The risk factors of overlap syndrome were age &gt;40 years (p = 0.002), obesity (p = 0.002), nonsteroidal anti-inflammatory drug and/or aspirin intake (p = 0.004) and tobacco smoking (p = 0.007). Among total patients with the heartburn/uninvestigated dyspepsia overlap syndrome, only 33.3% systemically had proton pump inhibitors, and only 17.4% had a prokinetic therapy.Conclusion. The heartburn/uninvestigated dyspepsia overlap syndrome is an actual issue in the Krasnoyarsk population. Attention is warranted to this problem to optimise treatment and prevention measures.

Characteristics of unintentional ingestion of oral non-steroidal anti-inflammatory drugs and analgesics in preschool children.

We characterised accidental ingestion of non-steroidal anti-inflammatory drugs and non-opioid analgesics in children aged 0–5 years between 2009 and 2019 by analysing records of telephone consultations with the Croatian Poison Control Centre (CPCC) and cases treated at the Children’s Hospital Zagreb (CHZ). Among the total of 466 identified cases (411 from CPPCC records and 55 from CHS hospital records), the most frequently ingested drugs were ibuprofen (47 %), paracetamol (20 %), ketoprofen (15 %), and diclofenac (11 %). In 94 % of the cases unsupervised children ingested the drug left within their reach. The remaining 6 % were dosing errors by parents or caregivers and involved liquid formulations as a rule. Our findings can serve as real-life examples informing preventive measures.

Safety, Outcomes, and Recommendations for Two-Step Outpatient Nonsteroidal Anti-Inflammatory Drug Challenges

Nonsteroidal anti-inflammatory drug (NSAID) outpatient challenge protocols are not standardized. They vary in clinical practice and can be time- and resource-intensive to perform. To investigate the safety and outcomes of two-step outpatient NSAID challenges to evaluate patients with non-aspirin-exacerbated respiratory disease (AERD)-related NSAID hypersensitivity. We conducted a retrospective study of patients with a history of NSAID allergy who underwent outpatient NSAID challenges under allergist supervision. Individuals with AERD were excluded. Patient demographics, NSAID reaction history, and drug challenge details and outcomes were collected. A total of 249 patients (mean age, 51.6 years; 63.5% female) underwent 262 NSAID challenges. Of these, 224 challenges were negative (85.5%). Thirty challenges resulted in an immediate reaction during the challenge procedure (11.5%) and eight resulted in delayed reactions (3.1%). Three individuals with immediate reactions required treatment with intramuscular epinephrine. Factors associated with a positive NSAID challenge included a prior reaction occurring within 5 years of drug challenge (odds ratio [OR]= 3.66; 95% confidence interval [CI], 1.67-8.44), a prior immediate reaction within 3 hours of NSAID ingestion (OR= 2.45; 95% CI, 1.12-5.57), a history of cross-reactive NSAID hypersensitivity to multiple NSAIDs (OR= 2.97; 95% CI, 1.23-6.91), and the presence of comorbid chronic spontaneous urticaria (OR= 2.95; 95% CI, 1.35-6.41). More than 85% of two-step non-AERD NSAID drug challenges were negative for an immediate or delayed reaction, which allowed patients to use at least one clinically indicated NSAID. Challenge reactions were generally mild. Two-step NSAID challenge protocols can be safely performed in the outpatient setting.

Sauna dehydration as a new physiological challenge model for intestinal barrier function

The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

Construct Validity of the Routine Assessment of Patient Index Data 3 (RAPID3) in the Evaluation of Axial Spondyloarthritis.

Although there are different tools to evaluate axial spondyloarthritis (axSpA), they are hardly used in routine clinical practice due to time constraints. The Routine Assessment of Patient Index Data 3 (RAPID3) is a composite measure feasible for use as a sole metric in busy clinics. We aimed to test its measurement properties in patients with axial SpA in a real-world clinical setting. This cross-sectional study included 131 consecutive patients with axial SpA. The convergent (Spearman ρ) and discriminant (receiver-operating characteristic [ROC] curve analysis) validity of RAPID3 were tested against several axSpA-specific measures (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS], Bath Ankylosing Spondylitis Functional Index [BASFI], and modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). A multivariate model was built to detect disease factors associated with RAPID3 remission (values ≤ 3). The study included 82 men and 49 women, with a median age of 55 (IQR 46-61) years, and a median disease duration of 11 (IQR 6-24) years. Mean RAPID3 was 9.45 ± 6.7. The BASDAI showed moderate correlation with ASDAS (ρ 0.66, P < 0.0001), but higher correlations with BASFI (ρ 0.78, P < 0.0001) and RAPID3 (ρ 0.75, P < 0.0001). The ASDAS had moderate correlations with BASFI, BASDAI, and RAPID3 (ranges 0.66-0.68, P < 0.0001). Higher correlations were found between BASFI and BASDAI (ρ 0.78, P < 0.0001), and BASFI and RAPID3 (ρ 0.73, P < 0.0001). The mSASSS did not show any correlation with any of the above composite measures. κ agreement between RAPID3 remission and other SpA remission criteria was moderate (κ 0.46-0.56). The RAPID3 thresholds to define remission ranged from values ≤ 2 to ≤ 6 with areas under the ROC curve between 0.86-0.91. Female sex (OR 0.34, 95% CI 0.12-0.90, P = 0.03) and nonsteroidal antiinflammatory drug intake (OR 0.26, 95% CI 0.10-0.66, P = 0.005) were independently associated with lower odds of achieving RAPID3 remission. RAPID3 demonstrated construct validity in this cross-sectional study. This index can be useful for a more comprehensive assessment of axSpA in busy clinical settings.

Treatment of ankylosing spondylitis during pregnancy

Aims of the trial – to study the frequency of drug use in pregnant women with ankylosing spondylitis (AS), to determine the effect of discontinuation of drugs of various groups, as well as the dose of non-steroidal anti-inflammatory drugs (NSAIDs) used, on AS activity during gestation.Material and methods. 50 pregnancies in 49 patients with AS that met the modified New York criteria of 1984. The average age of the patients was 31.7±4.9 years, the duration of the disease was 134.4±85.8 months. The visits were conducted at 10–11, 20–21 and 31–32 weeks of gestation. The BASDAI in the month of conception and in the I, II and III trimesters of pregnancy was: 1.4 [0.6; 3.3], 2.3 [1.2; 4.4], 2.8 [1.4; 4.2] and 2.2 [1.6; 4.0], respectively. The total dose of NSAIDs was determined by the NSAID intake index (Dougados M., 2011).Results and discussion. NSAIDs. After inclusion in the study, the drug of choice was ibuprofen, which was canceled for all women not later than on 32 week of gestation. At the time of conception and in the first, second and third trim. NSAIDs were taken by 23 (46%), 20 (40%), 30 (60%) and 21 (43.8%) women, respectively. NSAIDs intake index in I trimester (5.8 [2.9; 11.8]) was lower than before pregnancy (28.6 [16.7; 50]) and in II (15.5 [4.7; 30.9]) and III trimesters (24.4 [9.5; 50]) (p&lt;0.05). No relationship between the index of ibuprofen intake, as well as the fact of withdrawal of NSAIDs and AS activity throughout gestation was found. Sulfasalazine (SS) in correspondence with arthritis was taken 3 months before conception by 11 (22%) women, during pregnancy – by 6 (12%) women at a dose of 1.25±0.25 g. Withdrawal of SS was not associated with recurrence of arthritis. Glucocorticoids (GC) at a dose of 7.5±2.5 mg 3 months before pregnancy and in the I, II and III trimesters of pregnancy were taken by 1 (2%), 4 (8%), 8 (16%) and 10 (20.8%) women, of whom 1 patient had arthritis and 1 had inflammatory bowel disease. The rest of the patients received GC due to high AS activity due to axial manifestations and the unavailability of TNFα inhibitors. Against the background of taking GC, the AS activity did not decrease: BASDAI in the II and III trimesters was 5.5±0.6 and 5.8±1.3 (p&gt;0.05). TNFα inhibitors: 3 months before pregnancy and in the trim. of pregnancy were taken by 11 (22%), 7 (14%), 6 (12%) and 2 (4.2%) patients. In those who canceled therapy (both independently and on the recommendation of a rheumatologist) on the eve of pregnancy, an increase in AS activity was noted; BASDAI in the month of conception and in I, II, III trimesters was: 2.7 [0.8; 3.5], 5.1 [3.1; 5.9], 5.5 [5; 6] and 6.7 [5.3; 7.3] (p&lt;0.05) compared to the month of conception. Cancellation of TNF-α in the month of conception was a risk factor for high AS activity (BASDAI&gt;4) in the II trimester (OR=30.4; 95% CI: 1.5–612.3; p=0.03) and in the III trimester (OR=32.7; 95% CI: 1.6–662.2; p=0.02).Conclusion. NSAIDs and GC in low doses do not reduce the activity of AS. Withdrawal of TNF-α inhibitors on the eve of pregnancy is a predictor of high AS activity. It is necessary to increase the knowledge of rheumatologists and patients about the therapeutic possibilities during pregnancy to avoid unjustified drug withdrawal.

Poor Responsiveness to Low-Dose Aspirin Contributes to Persistent In Vivo Platelet Activation in Polycythemia Vera

▪Introduction . Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by peripheral erythrocytosis, increased thrombotic risk affecting morbidity and mortality. Low-dose aspirin once-daily (od) is currently recommended for cardiovascular prevention in PV. However, it has been recently suggested that aspirin should be used at 100 mg twice-daily (bid) in PV patients at high cardiovascular risk (JAK2V617F allelic burden, age >60 years) on the assumption of a shorter lasting antiplatelet effect, similarly to essential thrombocythemia. However, pharmacological and clinical data supporting the need for a bid ASA regimen in PV are missing.Methods . We studied the platelet responsiveness to standard aspirin (100 mg od) in PV patients, assessed at the end of the 24-h dosing interval. Patients were diagnosed according to the WHO 2008 criteria, were all on od low-dose aspirin and underwent a run-in phase (7-10 days) where aspirin tablets were always ingested at breakfast. Routine hematochemistry, genotype and allelic burden, clinical characteristics and history, medications were recorded. Serum thromboxane B2 (sTXB2) was measured as ex vivo biomarker of aspirin pharmacodynamics, urinary 11-deidro-TXB2 (TXM) as in vivo index of platelet activation, the major urinary prostacyclin metabolite, 2,3 dinor 6-keto-PGF1α (PGIM), the urinary isoprostane 8-iso-PGF2α and plasma salicylic acid esterase activity.Results . Forty-nine patients (67±10 years, 16 females) on aspirin for ≥1 month gave their informed consent; aspirin compliance and non-steroidal anti-inflammatory drug intake were checked by phone calls and patient's interview on the day of the visit. Nine patients were on phlebotomy only, while the remaining patients were on phlebotomy and hydroxyurea to keep the hematocrit <45%. Average hematologic values were: hematocrit 43.8±3%; erythrocytes 5.3±1.3x106/µL; leukocytes 9.1±4.3x103/µL, platelets 359±165x103/µL, immature platelets 11.8±7.4x103/µL. The median sTXB2 value was 8.6 [2-50] ng/ml, urinary TXM 509 [205-3428] pg/mg creatinine, 8-iso-PGF2α 768 [234-2104] pg/mg creatinine, PGIM 172 [120-275] pg/mg creatinine, plasma esterase activity 53 [47-60] µmol/L salycilic acid/min. Overall, sTXB2 significantly (p<0.01) correlated with immature platelets (rho=0.46), erythrocyte count (rho=0.41), leukocytes (rho=0.39). Patients were then divided according to sTXB2 tertiles, and patients in the lowest tertile showed sTXB2 levels within the expected range (3.4 [2.4-4.2] ng/ml, Figure). The patients in the upper tertile of sTXB2 levels (19.8 [15.3-40.9] ng/ml) were characterized by significantly (p<0.05) higher erythrocyte counts, total platelet counts, and immature platelets (p=0.05), while age, JAK2V617F allelic burden, leukocytes, hematocrit, hemoglobin, and sex distribution were comparable across tertiles. Urinary TXM significantly (p<0.05) correlated with sTXB2 (rho=0.39 and Figure), disease duration (rho=0.33), and leukocytes (rho=0.33). By multivariable analysis, only sTXB2 (p=0.009) positively predicted urinary TXM excretion. Urinary PGIM correlated with 8-iso-PGF2α excretion but not with TXM. Plasma esterase activity correlated with hemoglobin levels (rho=0.33, p=0.04), but not with the hematocrit, erythrocyte count, urinary TXM or sTXB2. JAK2V617F burden was significantly associated with polymorphonucleate count (rho=0.65), hemoglobin (rho=-0.49), and male sex (rho=0.41) while it was unrelated to previous thrombosis, sTXB2, urinary TXM and PGIM. By multivariable analysis JAK2V617F allelic burden predicted leukocyte counts only.Conclusions . A fraction of PV patients characterized by high erythrocyte, platelet and immature platelet count have a reduced response to a standard regimen of low-dose aspirin, which may contribute to persistently enhanced in vivo platelet activation. An improved antiplatelet regimen should be tested in these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Early-Life Exposure to Antibiotics and Risk for Crohn's Disease: A Nationwide Danish Birth Cohort Study.

Early-life antibiotic use can alter the intestinal flora and modify the risk of developing Crohn disease (CD), but rigorous epidemiological evidence is limited, with inconsistent results. We identified all children born in Denmark from 1995 to 2009 and followed them from birth until death, emigration, a diagnosis of CD, or January 1, 2013. Using Cox regression, we assessed the association between antibiotic exposure in the first year of life and subsequent risk for CD, adjusting for sex, degree of urbanization, birth order, birth year, route of delivery, gestational age, smoking during pregnancy, intake of nonsteroidal anti-inflammatory drugs in the first year of life, and family history of CD. During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children. Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4; 95% confidence interval [CI], 1.1-1.8), with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1; 95% CI, 2.0-8.5). A family history of CD did not modify these risk associations. The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16‰ (95% CI, 0.11‰-0.22‰) compared to 0.11‰ (95% CI, 0.08‰-0.15‰) for children unexposed to antibiotics in their first year of life. Antibiotic use in the first year of life is associated with a modestly increased risk for CD, although the absolute risk is very low.