Acetaminophen is an extremely common drug with many implications for its analgesic and antipyretic properties. It has a unique mechanism of action and downstream effects that separate it categorically from non-steroidal anti-inflammatory drugs. These differences come with potential adverse effects that range from mild drug reactions to severe life-threatening emergencies. While acetaminophen's toxic liver effects are well known, a lesser-known adverse effect of this drug is its association with the development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These dermatological emergencies involve similar pathological processes, including apoptosis of the epidermis and sloughing of the dermis and mucosa from the underlying layers with a positive Nikolsky sign. Currently, SJS and TEN are considered immune-mediated type IV hypersensitivity reactions predominantly involving CD8+ T lymphocytes. Other immune mediators, including regulatory T cells, natural killer cells, interleukins, and drug metabolites are speculated to be involved, but their mechanisms have not been entirely determined. These conditions are differentially diagnosed by the percentage of body area affected with SJS and TENS, involving &lt;10% and &gt;30%, respectively. Genomic variations in human leukocyte antigens (HLA) genes have been implicated in the susceptibility and severity of acetaminophen-induced SJS/TENS, however, details of these interactions remain unclear. Acetaminophen’s widespread use and the morbidity of its associated skin pathologies SJS and TENS warrant an in-depth examination of the causative processes involved in their pathogenesis. It is critical that both physicians and patients be made aware that while acetaminophen is widely tolerated by most individuals, severe and potentially fatal interactions do occur, and further investigation is necessary to reduce these adverse effects. 

/pdf/association-of-acetaminophen-with-stevens-johnson-syndrome-2pf675et.pdf

Association of Acetaminophen With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Pharmacologic Considerations and Treatment Options

The COVID-19 pandemic, which started in early 2020, has been a great source of stress for almost every person all around the world. However, this is particularly true for children. It is necessary to fully address the stress-related psychosocial issues connected with the pandemic, solely in children. Play is important for children’s development, as it is a natural activity for every child. Through play and play-based interventions, children can communicate non-verbally, symbolically, and in an action-oriented manner. Therefore, play-based interventions may have the potential to be one of the coping strategies used by children who experience stress, especially during the COVID-19 pandemic. The aim of this narrative review was to show how play-based activities could help children deal with stress related to the COVID-19 pandemic in the non-clinical population. A systematic search of the literature in various databases was performed. The initial search provided 5,004 potentially eligible studies in various databases, and 42,201 records identified from Google Scholar. After excluding studies not meeting the inclusive criteria, nine papers were selected for this narrative review. This narrative review showed findings that play-based activities can have a positive effect during the COVID-19 pandemic on different stress levels in the children population. Additionally, the findings of this review highlight the importance of further research and implementation of play into many aspects of children’s life.

Play as a Stress-Coping Method Among Children in Light of the COVID-19 Pandemic: A Review

Ibuprofen is an essential nonsteroidal anti-inflammatory drug (NSAID) which is still inaccessible to more than 100 million patients worldwide. Although three elegant continuous-flow approaches toward this NSAID have been developed, the major defect of requiring the use of a stoichiometric amount of highly toxic, corrosive, and expensive oxidizing reagents (such as di(acetoxy)phenyl iodide (PhI(OAc)2) and iodine monochloride (ICl)) prevents their application in industrial manufacturing. Herein, a novel and catalytic synthesis of ibuprofen from commercially available isobutylbenzene is performed by a linear continuous-flow sequence involving four chemical transformations without conducting solvent exchanges or intermediate purifications. This newly developed proof-of-principle regime provided access to ibuprofen in a global yield of 80.6% with an average of 94.7% for each step in a total reaction time of 32.5 min, corresponding to a throughput of 15.22 g/h. 

Scalable and Integrated Four-step Continuous-Flow Synthesis of Ibuprofen Using a Zinc-Catalyzed 1,2-Aryl Migration Strategy

Osteoarthritis is a growing public health concern, affecting millions of people worldwide. With progressively worsening joint function and pain, management of osteoarthritis is important to ensure high quality of life for patients. Treatment includes a combination of pharmacologic agents and non-pharmacologic methods such as exercise and physical therapy. However, if multiple treatments fail to improve symptoms, joint replacement surgery is the final course of action. When the new coronavirus, SARS-CoV-2 (COVID-19), was declared a pandemic, all aspects of osteoarthritis treatment become affected. Due to increased public health measures, non-pharmacologic modalities and elective surgeries became limited in accessibility. Additionally, there were concerns about the interaction of current medications for osteoarthritis with the virus. As a result of limited options for treatment and quality of life of patients was negatively impacted, especially in those with severe osteoarthritis. Furthermore, a backlog of joint replacement surgeries was created which could take up to several months or years to address. In this review, we describe the impact COVID-19 had on osteoarthritis management as well as tactics to deal with the large caseload of surgeries as operative rooms begin to re-open for elective surgeries. 

Challenges with patient management of osteoarthritis during the COVID-19 pandemic: review

Functionalized multiwalled carbon nanotubes (f-MWCNTs) are attractive additions for ultrafiltration (UF) membrane blending modification due to their outstanding physicochemical properties and ease of manufacture. As a result, the impact of f-MWCNTs on the surface characteristics and microstructure of the charged UF membranes, as well as the possibility of a synergistic effect on the removal efficiency of typical micropollutants, makes this an interesting and practical topic to investigate. In this study, a charged poly(m-phenylene isophthalamide) (PMIA) composite UF membrane modified by f-MWCNTs was prepared using a one-step phase transformation method. The association between membrane microstructure and ibuprofen removal efficiency was further studied by varying the kinds of MWCNT functional groups and three critical membrane preparation parameters (f-MWCNT content, membrane thickness, and heat treatment duration). The findings revealed that a 0.2 wt % carboxylated MWCNT (c-MWCNT) loading was required to create membranes with excellent hydrophilicity, permeability, and ibuprofen (IBU) retention. The fluctuation in solution pH has a substantial influence on the membrane's surface charge properties and IBU retention. The addition of c-MWCNT rendered the surface of the PMIA composite membrane more negatively charged than the pristine PMIA membrane, and the improved electrostatic exclusion effect resulted in an approximately 4-fold improvement in IBU retention (from 11% to 43%) in the pH range of 3–9. This study presents a simple and practical strategy for creating a negatively charged and antipollution PMIA composite UF membrane incorporating f-MWCNTs, which is regarded as a promising option for reducing the environmental impact of pharmaceuticals in safe drinking water treatment and the production of high-quality reusable water. 

A Charge-Enhanced Functionalized MWCNT/poly(m-Phenylene Isophthalamide) Ultrafiltration Membrane for Improved Ibuprofen Removal from Water

We aimed to investigate whether ibuprofen use, compared with other non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs), cyclooxygenase-2 inhibitors (COX-2i) or paracetamol, increases the risk of coronavirus disease 2019 (COVID-19) diagnosis or hospitalisation.A prevalent user and active comparator cohort study.Two US claims databases (Open Claims and PharMetrics Plus) mapped to the Observational Medical Outcomes Partnership Common Data Model.Insured patients with a history of osteoarthritis or back pain and receiving ibuprofen, other ns-NSAIDs, COX-2i or paracetamol between 1 November, 2019 and 31 January, 2020 (study enrolment window 1) or between 1 February, 2020 and 31 October, 2020 (study enrolment window 2).Large-scale propensity score matching and empirical calibration were used to minimise confounding. Incidence and hazard ratios of COVID-19 diagnosis and hospitalisation according to drug/s use were estimated and pooled in the same study period across data sources using a fixed-effects meta-analysis. Index treatment episode was the primary risk evaluation window, censored at the time of discontinuation.A total of 633,562 and 1,063,960 participants were included in periods 1 and 2, respectively, for the ibuprofen versus ns-NSAIDs comparison, 311,669 and 524,470 for ibuprofen versus COX-2i, and 492,002 and 878,598 for ibuprofen versus paracetamol. Meta-analyses of empirically calibrated hazard ratios revealed no significantly differential risk of COVID-19 outcomes in users of ibuprofen versus any of the other studied analgesic classes: hazard ratios were 1.13 (0.96-1.33) for the ibuprofen-ns-NSAIDs comparison, 1.03 (0.83-1.28) for the ibuprofen-COX-2i comparison and 1.13 (0.74-1.73) for ibuprofen-paracetamol comparison on COVID-19 diagnosis in the February 2020-October 2020 window. Similar hazard ratios were found on COVID-19 hospitalisation and across both study periods.In patients with osteoarthritis or back pain, we found no differential risks of incident COVID-19 diagnosis or COVID-19 hospitalisation for ibuprofen users compared with other ns-NSAIDs, COX-2i or paracetamol. Our findings support regulatory recommendations that NSAIDs, including ibuprofen, should be prescribed as indicated in the same way as before the COVID-19 pandemic, especially for those who rely on ibuprofen or NSAIDs to manage chronic arthritis or musculoskeletal pain symptoms. 

/pdf/risk-of-covid-19-diagnosis-and-hospitalisation-in-patients-3jrm2jit.pdf

Risk of COVID-19 Diagnosis and Hospitalisation in Patients with Osteoarthritis or Back Pain Treated with Ibuprofen Compared to Other NSAIDs or Paracetamol: A Network Cohort Study

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Risk of COVID-19 Diagnosis and Hospitalisation in Patients with Osteoarthritis or Back Pain Treated with Ibuprofen Compared to Other NSAIDs or Paracetamol: A Network Cohort Study