Prescription Of Anti-inflammatory Drugs Research Articles

Physicians’ attitudes toward gastroprotective strategies for nonsteroidal anti-inflammatory drug prescription

Introduction There is a paucity of information regarding providers’ attitudes toward gastric-protective strategies with concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs). We aimed to assess gastric-protective strategies used upon prescribing NSAIDs and providers’ awareness of societal guidelines for preventing NSAID-induced gastric complications. Methods A standardized 10-item questionnaire was sent to all orthopedic providers in North Carolina and South Carolina. The survey design and refinement were based on a literature review, item generation, and small and large focus group discussions. Results Forty-two orthopedists responded to the survey (response rate 16%). The most frequently used NSAIDs were meloxicam (79%), naproxen (69%), and ibuprofen (64%). NSAIDs were most commonly prescribed on an as-needed basis (52%), followed by <3 months (43%). The most common indications were degenerative arthritis (95%) and herniated disk (45%). Gastrointestinal adverse effects of NSAIDs were managed by discontinuing NSAID therapy (73%) or switching to a cyclooxygenase-2 (COX-2) inhibitor (40%). A small proportion were managed by referring to another physician (36%). Some clinicians prescribed gastric prophylaxis for patients at high risk for NSAID-induced gastric complications (24%). The academic setting was significantly associated with gastric prophylaxis and frequent assessment for NSAID-induced gastric adverse events. Providers with >20 years of experience showed similar trends. In low-risk patients, compliance with gastroprotective prophylaxis prescription was low (5%). Most providers were unaware of the societal guidelines for NSAID-induced gastric complications or the preventive strategies. Conclusion Prescription of gastric-protective medications with concurrent NSAID therapy is relatively low among orthopedists. Academic setting and higher years of experience showed a significant trend toward more gastric-protective medication prescription, COX-2 inhibitor use, and frequent assessments for gastric adverse events when prescribing NSAID therapy. Provider education on the latest societal guidelines and computer-based alerts can increase compliance and assessment for NSAID-induced gastric complications and preventive strategies.

Nonsteroidal Anti-inflammatory Drug (NSAID) Prescriptions in Living Kidney Donors

Nonsteroidal Anti-inflammatory Drug (NSAID) Prescriptions in Living Kidney Donors

Nonsteroidal anti-inflammatory drug (NSAID) prescribing after gastrojejunostomy: A preventable cause of morbidity

ObjectiveStudy findings showing an association between nonsteroidal anti-inflammatory drug use and marginal ulcer, a significant cause of morbidity after gastrojejunostomy, have been inconsistent. This study aimed to evaluate this relationship in large cohort. MethodsThis retrospective cohort included adult patients with a history of gastrojejunostomy documented between 2004 and 2023. The electronic medical record was queried for nonsteroidal anti-inflammatory drug prescriptions, marginal ulcer diagnosis, and comorbidities. Multivariable logistic regression was performed to assess the association between marginal ulcer and nonsteroidal anti-inflammatory drug exposures, controlling for smoking, Helicobacter pylori history, acid-suppressing therapy, diabetes, age, and sex. ResultsDuring the study period, 6,888 patients with a history of gastrojejunostomy were identified, of whom 45.2% (n = 3,115) of patients were exposed to an nonsteroidal anti-inflammatory drug and 10.12% (n = 697) developed a marginal ulcer. On multivariable analysis, the risk of marginal ulcer was found to be dose-dependent, with increasing odds of marginal ulcer with an increasing number of nonsteroidal anti-inflammatory drug exposures from odds ratio 1.67 (95% confidence interval, 1.37–2.02) with 1–2 nonsteroidal anti-inflammatory drug exposures to odds ratio 2.42 (95% confidence interval, 1.79–3.24) with >8 nonsteroidal anti-inflammatory drug exposures. Acid-suppressing therapy was found to be protective (odds ratio, 0.61; 95% confidence interval, 0.52–0.73). Over the last decade, the number of nonsteroidal anti-inflammatory drugs prescribed to patients with gastrojejunostomy has significantly increased from 15.87 prescriptions per 1,000 patients per year to 531.02 per 1,000 patients per year (R2 = 0.91, P < .001). ConclusionMarginal ulcer after gastrojejunostomy is associated with nonsteroidal anti-inflammatory drug prescriptions in a dose-dependent manner. Although acid-suppressing therapy appears protective for marginal ulcer, quality improvement efforts should focus on diminishing nonsteroidal anti-inflammatory drug prescribing in this population.

Massage Therapy Utilization in the Military Health System.

Massage therapy is an evidence-based approach for pain management. Information regarding its utilization in the Military Health System (MHS) is lacking. The goal of this study is to evaluate massage therapy utilization patterns across the MHS to include who receives (patient characteristics and diagnoses) and provides (e.g., massage therapists) massage therapy and where (e.g., clinic type). Medical record data of adult TRICARE Prime enrollees receiving outpatient massage therapy (Current Procedural Terminology codes: 97124 and 97140) from June 1, 2021, to May 31, 2023, were extracted from the MHS Data Repository. After identifying the index massage therapy visit, records for 6 months pre- and post-index were included. Descriptive statistics described massage therapy utilization patterns overall. Bivariate analysis compared patients who received massage therapy from massage therapists versus nonmassage therapist clinicians. Of patients who received massage therapy (n = 179,215), the median number of visits was 2 (interquartile range 1 to 4), the median age was 32 years (interquartile range 25 to 40), they were mostly assigned male (72%), White (53%), Senior Enlisted (51%), with a musculoskeletal diagnosis (90%), and recent non-steroidal anti-inflammatory drug (NSAID) prescription (58%). Massage therapy was primarily delivered by physical therapists (49%) in physical therapy clinics (74%). Massage therapists provided 0.2% of massage therapy. Patients who received massage therapy from massage therapists versus nonmassage therapists significantly varied across several patient and care characteristics. While massage therapy codes are documented frequently, massage therapists do not commonly provide massage therapy relative to nonmassage therapist providers. Access to massage therapists may be stymied by both lack of massage therapists and need for tertiary pain management referrals to access massage therapist-delivered care. Future research will leverage a health equity framework to (1) evaluate accessibility to massage therapy provided by massage therapists and (2) evaluate real-world evidence of massage therapy effectiveness.

Necrotizing soft-tissue infection of the upper limb: A single-center study of 24 cases

ObjectivesNecrotizing soft-tissue infection and necrotizing fasciitis of the upper limb are infrequent. Studies are rare, and often include other anatomical regions. The specificities and particularities of this pathology are not well known. The aim of this study was to report diagnosis and treatment aspects. MethodsA retrospective study was conducted over 10 years on every patient treated for necrotizing fasciitis of the upper limb with clinical, bacteriological and histological confirmation. One hundred ninety-eight items were extracted for each patient concerning clinical, biological, radiological and therapeutic data. ResultsDuring 10 years, 24 patients were diagnosed with necrotizing fasciitis of the upper limb: 18 males, 6 females; mean age, 59.9 years; mean body mass index, 25. Local erythema, pain and fever were the most frequent symptoms. Skin necrosis was present in fewer than 40% of patients.Sixteen cases (66.6%) had prior skin lesions and/or an entry point on the limb. Ten had non-steroidal anti-inflammatory drug prescription before acute symptom onset (42%), requiring intensive care unit admission.Treatment comprised surgical resection, resuscitative measures, antibiotic therapy and reconstructive surgery. Seven patients (30.4%) had 1 session of cutaneous excision, and the others had more than 2. Microbiological analysis found mono-microbial beta-hemolytic group A streptococci (BHGAS) infection in 14 patients (58.4%). Antibiotics were prescribed in 91% of cases before surgery, and in 100% after. The most frequently prescribed substance was clindamycin (18 patients, 75%).Ten patients (42%) stayed in the intensive care unit during treatment.Seventeen patients (70.8%) had thin skin graft reconstruction, including 50% with dermal substitute. Five patients (20.8%) had partial upper limb amputation. Two patients (8.3%) died in the 30 days following diagnosis. ConclusionsThe death rate in necrotizing fasciitis of the upper limb was rather low but the amputation rate was higher than in other locations.This study shows the specific clinical, biological and treatment features of this rare but serious pathology of the upper limb.

Development of a Machine Learning Model to Predict the Use of Surgery in Patients With Rheumatoid Arthritis.

One in five patients with rheumatoid arthritis (RA) rely on surgery to restore joint function. However, variable response to disease-modifying antirheumatic drugs (DMARDs) complicates surgical planning, and it is difficult to predict which patients may ultimately require surgery. We used machine learning to develop predictive models for the likelihood of undergoing an operation related to RA and which type of operation patients who require surgery undergo. We used electronic health record data to train two extreme gradient boosting machine learning models. The first model predicted patients' probabilities of undergoing surgery ≥5 years after their initial clinic visit. The second model predicted whether patients who underwent surgery would undergo a major joint replacement versus a less intensive procedure. Predictors included demographics, comorbidities, and medication data. The primary outcome was model discrimination, measured by area under the receiver operating characteristic curve (AUC). We identified 5,481 patients, of whom 278 (5.1%) underwent surgery. There was no significant difference in the frequency of DMARD or steroid prescriptions between patients who did and did not have surgery, though nonsteroidal anti-inflammatory drug prescriptions were more common among patients who did have surgery (P = 0.03). The model predicting use of surgery had an AUC of 0.90 ± 0.02. The model predicting type of surgery had an AUC of 0.58 ± 0.10. Predictive models using clinical data have the potential to facilitate identification of patients who may undergo rheumatoid-related surgery, but not what type of procedure they will need. Integrating similar models into practice has the potential to improve surgical planning.

Association between CNS-active drugs and risk of Alzheimer's and age-related neurodegenerative diseases.

As neuropsychiatric conditions can increase the risk of age-related neurodegenerative diseases (NDDs), the impact of CNS-active drugs on the risk of developing Alzheimer's Disease (AD), non-AD dementia, Multiple Sclerosis (MS), Parkinson's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) was investigated. A retrospective cohort analysis of a medical claims dataset over a 10 year span was conducted in patients aged 60 years or older. Participants were propensity score matched for comorbidity severity and demographic parameters. Relative risk (RR) ratios and 95% confidence intervals (CI) were determined for age-related NDDs. Cumulative hazard ratios and treatment duration were determined to assess the association between CNS-active drugs and NDDs at different ages and treatment duration intervals. In 309,128 patients who met inclusion criteria, exposure to CNS-active drugs was associated with a decreased risk of AD (0.86% vs 1.73%, RR: 0.50; 95% CI: 0.47-0.53; p <.0001) and all NDDs (3.13% vs 5.76%, RR: 0.54; 95% CI: 0.53-0.56; p <.0001). Analysis of impact of drug class on risk of AD indicated that antidepressant, sedative, anticonvulsant, and stimulant medications were associated with significantly reduced risk of AD whereas atypical antipsychotics were associated with increased AD risk. The greatest risk reduction for AD and NDDs occurred in patients aged 70 years or older with a protective effect only in patients with long-term therapy (>3 years). Furthermore, responders to these therapeutics were characterized by diagnosed obesity and higher prescriptions of anti-inflammatory drugs and menopausal hormonal therapy, compared to patients with a diagnosis of AD (non-responders). Addition of a second CNS-active drug was associated with greater reduction in AD risk compared to monotherapy, with the combination of a Z-drug and an SNRI associated with greatest AD risk reduction. Collectively, these findings indicate that CNS-active drugs were associated with reduced risk of developing AD and other age-related NDDs. The exception was atypical antipsychotics, which increased risk. Potential use of combination therapy with atypical antipsychotics could mitigate the risk conferred by these drugs. Evidence from these analyses advance precision prevention strategies to reduce the risk of age-related NDDs in persons with neuropsychiatric disorders.

First-contact physiotherapists' perceived competency in a new model of care for low back pain patients: a mixed methods study.

A new advanced practice model of care enables French physiotherapists to perform medical acts for low back pain (LBP) patients as first-contact physiotherapists (FCPs). The aim of this study is to determine the self-perceived competency of FCPs and to further explore factors underpinning this feeling. A mixed-methods explanatory sequential design was conducted. A survey was used to self-assess the perceived competency of FCPs in performing medical tasks. Semi-structured interviews were then performed to explore determining factors of perceived competency. Inductive thematic analysis was performed. Nine FCPs answered the survey and were interviewed (mean age 40.1, standard deviation [SD]: ±10.0). FCPs felt very competent with making medical diagnosis (3.44/4, SD: ±0.53), analgesic prescription (3.11, SD: ±0.78) and referring onward to physiotherapy (3.78, SD: ±0.55). They did not feel competent with nonsteroidal anti-inflammatory drug prescription (2.78, SD: ±0.67) and issuing sick leave certificate (2.67, SD: ±1.0). The main identified influencing factors were previous FCPs' experience, training, knowledge, collaboration with family physicians, high responsibility and risk management associated with decision-making. French FCPs appeared to have the necessary skills to directly manage LBP patients without medical referral. Future training focusing on analgesic prescription and issuing sick leave certificate is however needed.

Trends in the treatment of fibromyalgia in South Korea between 2011 and 2018: a retrospective analysis of cross-sectional health insurance data

ObjectivesFibromyalgia treatment trends vary globally; however, the trend in South Korea has not been investigated yet. This study aimed to analyse the fibromyalgia treatment trends in South Korea.DesignRetrospective, observational study...

A study of the impact of the COVID-19 pandemic on equine veterinary care in the UK.

During the COVID-19 pandemic, equine health care in the UK may have been adversely affected due to mandated changes in the delivery of veterinary healthcare and the potential for reduced health-seeking behaviour. Electronic patient records (EPRs) were analysed to describe veterinary activity for all equids under the active care of 20 veterinary practices in the UK in the 12 months before and after the introduction of the first UK lockdown. Pre-pandemic and pandemic levels of clinical activity were compared. Further comparisons of care, including immediate management and treatment, were made following a detailed review of EPRs from randomly selected subsets of equids under care in four time periods. All measures of activity and face-to-face interaction were lower in the early pandemic period than in the equivalent pre-pandemic period. Compared to pre-pandemic, the early pandemic was associated with a decrease in prophylactic care and non-urgent diagnostic imaging and an increase in systemic non-steroid anti-inflammatory prescription. Convenience sampling of veterinary practices may have limited the generalisability of the findings. The quality of EPRs was variable. While equine veterinary activity was significantly disrupted in the early pandemic period, there was a rapid return to pre-pandemic levels of activity. Subsequent lockdowns appeared to have had little effect on veterinary care.

Knowledge, attitudes and practices in HIV-related chronic inflammation and cardiovascular risk in Spain

BackgroundPeople with HIV (PWH) in suppressive antiretroviral treatment suffer from chronic inflammation-related comorbidities, mainly cardiovascular diseases. However, given the lack of specific evidence about inflammation in PWH, clinical guidelines do not provide recommendations for the management of this issue. To date, physician awareness of inflammation in PWH remains unclear. We analyzed the knowledge, attitudes, and practices (KAP) related to inflammation, particularly in the clinical management of PWH, of infectious disease specialists (IDS)/internists compared to other specialists treating inflammation directly (rheumatologists) or its cardiovascular consequences (cardiologists). MethodsA committee of IDS/internists treating PWH, cardiologists, and rheumatologists designed the KAP questionnaire. The survey was completed by 405 participants (135 physicians per specialty) stratified by Spanish geography, hospital size, and number of PWH under care (IDS/internists only). ResultsIDS/internists treating PWH scored higher than cardiologists and rheumatologists on knowledge of inflammation (5.5±1.4 out of 8 points vs. 5.2±1.3 and 4.6±1.4 points, respectively; p<0.05). Nevertheless, rheumatologists showed the most proactive attitude toward inflammation (i.e., biomarkers monitoring, anti-inflammatory drug prescription and cardiologist referral), followed by cardiologists and IDS/internists (13±3 of a total of 16 points vs. 11±3 and 10±3.3 points, respectively; p<0.05), irrespective of hospital size and years of experience. Most IDS/internists (59%) include inflammation in their therapeutic recommendations. However, in IDS/internists treating PWH, we observed a negative correlation between years of experience and concern about the clinical consequences of inflammation. ConclusionOur findings show that, compared to other specialists, infectious disease specialists/internists have high knowledge about inflammation in HIV infection, but, in the absence of scientific evidence to base their decisions on inflammatory markers, the therapeutic implications are scarce. The results support the need for more evidence on the monitoring and treatment of inflammation in PWH.

Using intervention mapping to design and implement a multicomponent intervention to improve antibiotic and NSAID prescribing.

Successfully changing prescribing behavior to reduce inappropriate antibiotic and nonsteroidal anti-inflammatory drug (NSAID) prescriptions often requires combining components into a multicomponent intervention. However, multicomponent interventions often fail because of development and implementation complexity. To increase the likelihood of successfully changing prescribing behavior, we applied a systematic process to design and implement a multicomponent intervention. We used Intervention Mapping to create a roadmap for a multicomponent intervention in unscheduled outpatient care settings in the Veterans Health Administration. Intervention Mapping is a systematic process consisting of six steps that we grouped into three phases: (i) understand behavioral determinants and barriers to implementation, (ii) develop the intervention, and (iii) define evaluation plan and implementation strategies. A targeted literature review, combined with 25 prescriber and 25 stakeholder interviews, helped identify key behavioral determinants to inappropriate prescribing (e.g. perceived social pressure from patients to prescribe). We targeted three desired prescriber behaviors: (i) review guideline-concordant prescribing and patient outcomes, (ii) manage diagnostic and treatment uncertainty, and (iii) educate patients and caregivers. The intervention consisted of components for academic detailing, prescribing feedback, and alternative prescription order sets. Implementation strategies consisted of preparing clinical champions, conducting readiness assessments, and incentivizing use of the intervention. We chose a mixed-method study design with a commonly used evaluation framework to assess effectiveness and implementation outcomes in a subsequent trial. This study furthers knowledge about causes of inappropriate antibiotic and NSAID prescribing and demonstrates how theoretical, empirical, and practical information can be systematically applied to develop a multicomponent intervention to help address these causes.

Older Adult-Onset of Inflammatory Bowel Diseases Is Associated With Higher Utilization of Analgesics: A Nationwide Cohort Study.

Patients with inflammatory bowel diseases (IBD) commonly require analgesic medications to treat pain, which may be associated with complications. We examined trends of analgesic use according to age at IBD onset. This nationwide cohort study included adults diagnosed with IBD between 1996 and 2021 in Denmark. Patients were stratified according to their age at IBD onset: 18-39 years (young adult), 40-59 years (adult), and older than 60 years (older adult). We examined the proportion of patients who received prescriptions for analgesic medications within 1 year after IBD diagnosis: strong opioids, tramadol, codeine, nonsteroidal anti-inflammatory drugs, and paracetamol. Multivariable logistic regression analysis was performed to examine the association between age at IBD onset and strong opioid prescriptions and the composite of strong opioid/tramadol/codeine prescriptions. We identified 54,216 adults with IBD. Among them, 25,184 (46.5%) were young adults, 16,106 (29.7%) were adults, and 12,926 (23.8%) were older adults at IBD onset. Older adults most commonly received analgesic prescriptions of every class. Between 1996 and 2021, strong opioid, tramadol, and codeine prescriptions were stable, while paracetamol prescriptions increased and nonsteroidal anti-inflammatory drug prescriptions decreased. After multivariable logistic regression analysis, older adults had higher adjusted odds of receiving strong opioid prescriptions (adjusted odds ratio 1.95, 95% confidence interval 1.77-2.15) and the composite of strong opioid/tramadol/codeine prescriptions (adjusted odds ratio 1.93, 95% confidence interval 1.81-2.06) within 1 year after IBD diagnosis compared with adults. In this nationwide cohort, older adults most commonly received analgesic prescriptions within 1 year after IBD diagnosis. Additional research is needed to examine the etiology and sequelae of increased analgesic prescribing to this demographic.

Knowledge, attitudes and practices in HIV-related chronic inflammation and cardiovascular risk in Spain

BackgroundPeople with HIV (PWH) in suppressive antiretroviral treatment suffer from chronic inflammation-related comorbidities, mainly cardiovascular diseases. However, given the lack of specific evidence about inflammation in PWH, clinical guidelines do not provide recommendations for the management of this issue. To date, physician awareness of inflammation in PWH remains unclear. We analyzed the knowledge, attitudes, and practices (KAP) related to inflammation, particularly in the clinical management of PWH, of infectious disease specialists (IDS)/internists compared to other specialists treating inflammation directly (rheumatologists) or its cardiovascular consequences (cardiologists). MethodsA committee of IDS/internists treating PWH, cardiologists, and rheumatologists designed the KAP questionnaire. The survey was completed by 405 participants (135 physicians per specialty) stratified by Spanish geography, hospital size, and number of PWH under care (IDS/internists only). ResultsIDS/internists treating PWH scored higher than cardiologists and rheumatologists on knowledge of inflammation (5.5±1.4 out of 8 points vs. 5.2±1.3 and 4.6±1.4 points, respectively; p<0.05). Nevertheless, rheumatologists showed the most proactive attitude toward inflammation (i.e., biomarkers monitoring, anti-inflammatory drug prescription and cardiologist referral), followed by cardiologists and IDS/internists (13±3 of a total of 16 points vs. 11±3 and 10±3.3 points, respectively; p<0.05), irrespective of hospital size and years of experience. Most IDS/internists (59%) include inflammation in their therapeutic recommendations. However, in IDS/internists treating PWH, we observed a negative correlation between years of experience and concern about the clinical consequences of inflammation. ConclusionOur findings show that, compared to other specialists, infectious disease specialists/internists have high knowledge about inflammation in HIV infection, but, in the absence of scientific evidence to base their decisions on inflammatory markers, the therapeutic implications are scarce. The results support the need for more evidence on the monitoring and treatment of inflammation in PWH.

A decade of water monitoring in a Mediterranean region: Pharmaceutical prioritisation for an upgraded analytical methodology

In order to evaluate the performance of wastewater treatment strategies and to foster water reclamation it is necessary to evaluate the removal of water pollutants such as pharmaceutical active compounds (PhACs). Therefore, the development and application of appropriate analytical methods for the monitoring of the most relevant ones is crucial. In this work, the occurrence data of 157 PhACs in different water bodies and wastewaters in Catalonia (Spain) in the last 10 years, as reported in circa 30 publications, was gathered and reviewed to select the 50 most relevant compounds, including 12 transformation products and metabolites. Historical data confirmed the high consumption and prescription of analgesic and anti-inflammatory drugs, together with psychiatric drugs and antibiotics. An analytical protocol based on solid-phase extraction preconcentration and further measurement by UHPLC-MS/MS was upgraded for the selected 50 compounds and applied to the characterisation of water samples from Catalonia and the Greek Islands, both areas suffering from water scarcity. Results showed similar PhAC concentration profiles in both countries except in the case of some compounds such as iopromide, venlafaxine, and gemfibrozil.

Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006–2021

This cross-sectional study examined nationwide real-world associations between anti-inflammatory agent fills and suicide-related death rates in 20-24-year-olds across the 21 Swedish regions during 2006-2021. Nationwide Swedish registers were used to compare regional year-wise suicide-related mortality (SRM) and dispensations for anti-inflammatory agents (ATC-code: M01) in 20-24-year-olds. Dispensations for paracetamol (ATC-code: N02BE01) was applied as a control variable. Associations between regional year-wise SRM and dispensation rates were analyzed by sex-stratified zero-inflated generalized linear mixed effect models (GLMM). Dispensation rates of paracetamol and inflammatory agents were designated as independent fixed effects variables, and year and region constituted random-intercept effects. Acetic acid derivatives and related substances (M01AB) and propionic acid derivates (M01A3) accounted for ∼71% of measured dispensation fills for anti-inflammatory agents. Diclofenac fills constituted ∼98% of the former category, whereas dispensations for Ibuprofen (∼21%), Naproxen (∼62%) and Ketoprofen (∼13%) constituted the most prescribed agents in the latter category. Regional yearly dispensation rates of anti-inflammatory agents in 20-24-year-old females were inversely associated with female SRM (β=-0.095, p=0.0393, 95% CI -0.186, -0.005) - independent of paracetamol rates, which were unassociated to SRM (p=0.2094). Results were confirmed in validation analyses for anti-inflammatory agents (OR=0.7232, p=0.0354, 95% CI [OR] 0.5347, 0.9781). No association was demonstrated in males (p=0.833). Anti-inflammatory agent dispensation rates were independently associated to lower suicide-related death rates in female 20-24-year-olds. This adds to growing evidence implicating inflammatory processes in mental disorders, warranting trials focusing on the suicide preventative potential of anti-inflammatories in young adults.

Fetal inflammatory response and risk for psychiatric disorders

Inflammation contributes to numerous neuropsychiatric disorders, especially those that first appear in childhood. Maternal intrauterine environment, including the placenta, has a role in brain development and risk for neuropsychiatric disorders. This study examines the link between fetal inflammatory syndrome (FIRS), which is placental inflammation in the peri-partem period, and neuropsychiatric disorders during childhood.This is a retrospective cohort study using data from electronic medical records over a 19-year period at one women’s hospital. The study includes 4851 children born with placentas meeting criteria for and 31,927 controls identified with normal placentas born during the same period. To be diagnosed with FIRS placenta must contain chorionic vasculitis and/or funisitis. Children had to be in study period for at least 5 years. The primary outcome of the study is incidence of neuropsychiatric disorders during childhood. The secondary outcomes were psychiatric medications prescribed, and psychiatric hospitalizations and treatment. Children born to placentas meeting criteria for FIRS were more likely to be diagnosed with neuropsychiatric disorders (OR = 1.21, CI 95% [1.09,1.35]). Specifically, they were more likely to be diagnosed with autism spectrum disorder (OR = 1.35, CI 95% [1.08, 1.67]), ADHD (OR = 1.27, CI 95% [1.07, 1.49]), conduct disorder (OR = 1.50, CI 95% [1.24, 1.81]), PTSD (OR = 2.46. CI 95% [1.21, 5.04]), adjusting for maternal history of psychiatric disorders, intra-partem substance use, and prescriptions of anti-inflammatory drugs. Children born with placental inflammation are at an increased risk to develop neuropsychiatric disorders. This has profound implications for future research, and early detection, monitoring, and treatment in these children.

Incidence and risk factors of warfarin therapy complications in community hospitals, central and eastern regions, Thailand: a retrospective, multicenter, cohort study

ObjectivesWarfarin, like many other anticoagulants, has been linked to an elevated risk of bleeding proportional to the amount of anticoagulation used. Not only was the incidence of bleeding raised by the dosage, but the subtherapeutic international normalized ratio (INR) was also associated with increased thrombotic events. This retrospective cohort and multi-center study evaluated the incidence and risk factors of warfarin therapy complications in community hospitals in Thailand’s central and eastern regions from 2016 to 2021.ResultsAmong 335 patients (683.90 person-year of follow-up), The incidence rate of warfarin complications was 4.91 events per 100 person-year. The independent factor associated with warfarin therapy complications was propranolol prescription (Adjusted RR: 2.29, 95%CI: 1.12–4.71). The secondary analysis was divided according to the outcome of the major bleeding and thromboembolic event. Major bleeding events, hypertension (Adjusted RR: 0.40, 95%CI: 0.17–0.95), amiodarone prescription (Adjusted RR: 5.11, 95%CI: 1.08–24.15), and propranolol prescription (Adjusted RR: 2.86, 95%CI: 1.19–6.83) were the independent risk factors. While in the major thrombotic event, non-steroidal anti-inflammatory drugs (NSAIDs) prescription was an independent factor (Adjusted RR: 10.65, 95%CI: 1.26–90.35).

High- vs. low-dose diclofenac and cardiovascular risks: a target trial emulation.

To examine the dose dependency of diclofenac's cardiovascular risks. Using Danish health registries and the target trial emulation design, we conducted a series of 300 nationwide cohort studies during 1996-2020, each mimicking the strict design criteria of a clinical trial. Adults eligible for inclusion had no recent non-steroidal anti-inflammatory drug prescriptions, contraindications (gastrointestinal diseases, thrombocytopenia, or heart failure), or conditions with low adherence (dementia or psychiatric disease). Diclofenac initiators were compared to healthcare-seeking non-initiators and head-to-head using an approximated high dose of ≥150mg/day vs. low dose of <150mg/day. Cox regression was used to compute the incidence rate ratio (IRR) of major adverse cardiovascular events (MACE) within 30 days following initiation. We adjusted for age, sex, calendar period, comorbidity, comedication, and socioeconomic position. Compared with non-initiators (n=3789 617), diclofenac initiators (n=1 894 834) had an approximately 50% increased rate of MACE (IRR 1.53, 95% confidence interval [CI]: 1.43-1.63), reflecting IRRs of 1.54 (95% CI: 1.40-1.69) for myocardial infarction, 1.29 (1.14-1.45) for ischaemic stroke, and 1.92 (1.71-2.16) for cardiac death. The risk increase was observed for most conditions with chronic pain, in particular headache (IRR 5.10, 95% CI: 1.46-17.85). The risk increase was similar for initiators of high- (IRR 1.55, 95% CI: 1.40-1.71) and low-dose diclofenac (IRR 1.52, 1.41-1.63), which was confirmed in a head-to-head analysis (IRR 1.01, 95% CI: 0.90-1.12). Initiators of high- and low-dose diclofenac had comparably increased cardiovascular risks. This finding provides evidence against the assumption that low-dose diclofenac is risk-neutral.

Population-Based Analysis of Nonsteroidal Anti-inflammatory Drug Prescription in Subjects With Chronic Kidney Disease

Pain is a prevalent symptom experienced by patients with chronic kidney disease (CKD) and appropriate management of pain is an important element of comprehensive care. Nonsteroidal anti-inflammatory drugs (NSAID) are known to be nephrotoxic in persons with CKD. This study examined the pattern of NSAID prescribing practices in a population based-cohort of patients with CKD. Retrospective cohort study using linked population-based health care data. Entire province of Alberta, Canada. All adults in Alberta with eGFR defined CKD G3 or greater between 2009 and 2017 were included. CKD was defined using at least 2 outpatient serum creatinine (SCr) greater than 90 days apart; the date of second SCr measurement was used as index date. We determined the incidence of hyperkalemia using the peak serum potassium. Prescription drug information was obtained from the Pharmaceutical Information Network (PIN) database. All patients were followed from the index date until March 31, 2019, with a minimum follow-up of 2 years. Prescription drug information and the follow-up laboratory testing of serum creatinine and serum potassium were obtained. Patients with kidney failure defined as eGFR < 15 mL/min per 1.73 m2, receiving chronic dialysis, or prior kidney transplant at baseline were excluded. A total of 170 574 adults (mean age 76.3; 44% male) with CKD were identified and followed for a median of 7 years; 27% were dispensed at least 1 NSAID prescription. While there was a trend toward fewer prescriptions in patients with more advanced CKD (P < .001), 16% of those with CKD G4 were prescribed an NSAID. Primary care providers provided 79% of the prescriptions. Among NSAID users, 21% had a follow-up serum creatinine (SCr) within 30 days of the index prescription. Data collected were from clinical and administrative databases not created for research purposes. The study cohort is limited to subjects who sought medical care and had a serum creatinine measurement obtained. Measurement of NSAID use is limited to those who were dispensed a prescription, over-the-counter NSAIDs use is not captured. Despite guidelines advocating cautious use of NSAIDs in patients with CKD, this study indicates that there is a discrepancy from best practice recommendations. Effective strategies to better support and educate prescribers, as well as patients, may help reduce inappropriate prescribing and adverse events.