The Association of Tumor Necrosis Factor Inhibitor Use With Incident Hypertension in Ankylosing Spondylitis: Data From the PSOAS Cohort

Objective Individuals with ankylosing spondylitis (AS) have a greater cardiovascular (CV) risk than those in the general population. The effect of tumor necrosis factor inhibitors (TNFis) on CV risk, including on the development of hypertension (HTN), remains unclear, with some data suggesting higher risk. We assessed the association of TNFi use with incident HTN in a longitudinal AS cohort. Methods Adults with AS enrolled in a prospective cohort in 2002–2018 were examined every 4–6 months. TNFi use during the preceding 6 months was ascertained at each study visit. We defined HTN by patient-reported HTN, antihypertensive medication use, or, on 2 consecutive visits, systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. We evaluated the association between TNFi use and the development of HTN with marginal structural models, estimated by inverse probability-of-treatment weighting, to account for time-dependent confounders and informative censoring. Potential confounders included age, sex, race, site, nonsteroidal antiinflammatory drug use, and disease activity. Results We included 630 patients without baseline HTN and with at least 1 year of follow-up. Of these, 72% were male, mean age was 39 ± 13 years, and 43% used TNFi at baseline. On follow-up (median 5 yrs), 129 developed incident HTN and 163 started on TNFi during follow-up. TNFi use was not associated with incident HTN (adjusted HR 1.10, 95% CI 0.83–1.37). Conclusion In our prospective AS cohort, TNFi use was not significantly associated with incident HTN.

Development of Fourier transform infrared spectrophotometric method for identification and determination of marketed metamizole tablet preparation

Metamizole is a nonsteroidal antiinflammatory drug (NSAID) that functions as an analgesic, antipyretic, and antiinflammatory. Examination of active substance contents is a requirement that must be met to ensure the quality of drug preparations. The aims of this study were to develop and validate the Fourier Transform Infrared spectrophotometric method for the quantitation of metamizole content in marketed tablet preparation. Identification and determination of metamizole contents by Fourier Transform Infrared spectrophotometric method used methanol solvent in the wavenumber range 4000 cm–1 to 650 cm–1. The results showed that the specific wavenumbers of metamizole were 1649.3 cm–1; 1623.3 cm–1; and 1589.7 cm–1; and the contents metamizole in marketed tablet preparation ranged from (97.954 ± 0.121)% to (104.541 ± 0.257)%. From the validation method, the recovery result is 100.129%; the relative standard deviation is 0.057%; the limit of detection is 2.09526 mg/mL; the limit of quantitation is 6.34928 mg/mL; and the range 40 mg/mL to 60 mg/mL. The quantitation of metamizole contents can be carried out by Fourier Transform Infrared spectrophotometric method with accurate and precise quantitation results.

Strength and Sterility of Stock and Diluted Carprofen Over Time

Carprofen, a nonsteroidal antiinflammatory drug, is a commonly used analgesic for laboratory animals. The manufacturerlabeling indicates the stock bottle may be stored and used for up to 28 d under refrigeration. However, institutional guidelines may vary in how long diluted carprofen solutions can be stored before they must be discarded. When administered to laboratory rodents, small volumes of the stock solution are diluted to provide accurate dosing and ease of administration. Because carprofen is formulated for use in companion animals (for example, dogs) and comes in larger volume multidose vials, the majority of carprofen at our institution is discarded before it can be used. In this study, we evaluated the amount of target ingredient present (strength), sterility, and endotoxin levels of both stock and diluted carprofen when stored in a variety of containers and at multiple temperature settings for up to 180 d, mimicking facets of typical use in laboratory animal research and medicine. We demonstrated that when refrigerated and stored in sterile vials, stock and diluted carprofen can be kept and used for up to 180 d while retaining strength and sterility. For short-term use, diluted carprofen can also be stored for up to 60 d at room temperature in conical tubes. These results will help establish scientifically justified storage conditions for carprofen to ensure that these agents remain appropriately potent and sterile for therapeutic use in laboratory animals.

Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study

Background Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells. Methods We conducted a cohort study using South Korea’s nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding. Results Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13–2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96–2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49–4.14). Conclusions While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.

Paediatric postoperative analgesia prescribing report card: “could do better”

Background: A key element of paediatric pain management is prescribing and dispensing analgesia. This process differs in children, putting them at greater risk of drug error. Methods: This study was a retrospective postoperative analgesia prescription chart review of children who had orthopaedic surgery in a tertiary hospital in Durban, South Africa. Patient records of 202 children, aged 6 months to 12 years, with 232 theatre visits were reviewed. Prescription charts were inspected for patient characteristics, evidence of good prescribing practice and data regarding the prescribing and administration of analgesia. Results: Of the 257 analysed charts 254 (99%) had paracetamol, 208 (81%) had an opioid and 49 (19%) had a nonsteroidal antiinflammatory drug (NSAID) prescribed. Underdosing was evident in all groups of analgesics prescribed. Opioids were more often prescribed with a pro-re-nata caveat and were the least correctly dispensed. There were no prescription charts in which all the requirements for good prescribing practice were complete. Conclusions: This study demonstrates a high rate of paediatric drug error in both the prescribing and dispensing of analgesia. Potential under-utilisation of NSAIDs in this orthopaedic population is also noted. Lack of knowledge or confidence needed by clinicians to adhere to principles of paediatric dosing and multimodal analgesia may be contributing factors. Issues pertaining to paediatric analgesia prescribing and dispensing are highlighted and should be targeted by institution and population specific interventions.