PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

INTAKE OF ACETAMINOPHEN SUPPRESSES ANTIVIRAL HUMORAL IMMUNE RESPONSES IN PATIENTS WITH RA FOLLOWING VACCINATION WITH ANTI SARS-CoV-2 mRNA BASED VACCINES

BackgroundAcetaminophen (APAP = paracetamol) may potentially impact vaccine-associated immune responses as the intake of APAP has been associated with a worse outcome in tumor patients receiving checkpoint inhibitors.[1]Different DMARD regimen have been shown to impair the humoral immune response to mRNA SARS-CoV-2 vaccines in patients with rheumatoid arthritis but the effect of paracetamol has not been explored thus far.ObjectivesTo analyse whether the intake of APAP may interfere with antiviral humoral immune responses following two doses of an anti-SARS-CoV-2 mRNA based vaccine in patients with rheumatoid arthritis (RA) on DMARD therapy.MethodsThe RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) was a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 healthy controls (HC). We performed a posthoc analysis of blood samples taken before the first vaccine dose (T0), two (T1) and three (T2) weeks after the first and second vaccine dose, and at 12 (T3) weeks. APAP intake was measured using ELISA. The antibody response (anti-S) to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The neutralizing activity NT50 at week 12 was assessed using an HIV-based pseudovirus neutralization assay against Wuhan-Hu-1.ResultsBaseline characteristics of participants are detailed in Table 1. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein at baseline). APAP was detected in serum samples from 34/73 (25%) RA patients and in 7/21 (33%) HC (least at one timepoint T0, T1 and/or T2). APAP intake in HC did not affect levels of anti-S at any timepoint and all HC developed potent neutralizing activity (NT50 ≥ 250) at week 12. RA patients, who tested positive for APAP at T1, showed comparable anti-S levels at T1, T2 and T3 compared to RA patients not exposed to APAP. The detection of APAP at T2 corresponded to lower anti-S levels at T2 (Figure 1 A, B). The detection of APAP at T2 was associated with a significantly lower SARS-CoV-2 neutralizing activity at week 12 compared to patients without perivaccination APAP exposure (p =0.04) (Figure 1 C).ConclusionA decrease of antiviral humoral immune responses was observed in RA patients (but not in HC) who were exposed to APAP at the time of the second mRNA vaccine dose compared to patients in whom APAP was not detected. Our data suggest that the use of paracetamol within the time period around vaccination may impair vaccine-induced immune responses in patients with an already higher risk for blunted immune responses.Reference[1]Bessede A et al. Ann Oncol 2022;33: 909-915Table 1.Baseline characteristics: RA patients and HC with/without APAP exposureRA APAP – n = 37RA APAP + n = 36p-valueHC APAP – n = 8HC APAP + n = 13p-valueAge (yrs), mean (± SD)62 (13)67 (10)0.07 (NS)45 (12)44 (14)0.90 (NS)Female sex, n (%)24 (65)19 (53)0.29 (NS)2 (25)5 (38)0.53 (NS)Vaccination type/schedulemRNA-1273, n (%)4 (11)8 (22.2)0.19 (NS)0 (0)0 (0)BNT162b2, n (%)33 (89)28 (77.8)0.19 (NS)8 (100)13 (100)RA disease characteristicsACPA ± RF, n (%)17/37 (46)19/36 (53)0.56 (NS)NANANARA disease duration (yrs ± SD)9.2 (9.8)10.2 (8.1)0.67 (NS)NANANADMARD therapycsDMARD-mono, n (%)13/37 (35)9/36 (25)0.35 (NS)NANANAbDMARD-mono/combo, n (%)16/37 (43)16/36 (44)0.92 (NS)NANANAtsDMARDs-mono/combo, n (%)8/37 (22)11/36 (31)0.38 (NS)NANANAPrednisone, n (%)15/37 (41)12/36 (33.3)0.52 (NS)NANANAMean daily dose prednisone (mg ± SD)4.6 ± 1.13.9 ± 2.30.39 (NS)NANANA* APAP = acetaminophenFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

IDDF2023-ABS-0045 Spatiotemporal immune landscape of Mas-driven pro-inflammatory microenvironment with hyperactivated glycolysis in acetaminophen-induced liver injury

IDDF2023-ABS-0045 Figure 1 IDDF2023-ABS-0045 Figure 2 IDDF2023-ABS-0045 Figure 3 IDDF2023-ABS-0045 Figure 4

The use of analgesics for intentional self-poisoning: Trends in U.S. poison center data.

In the U.S., intentional self-poisonings with analgesics that are available without a prescription increased from 2000 to 2018. Given concerns regarding mental health outcomes during the COVID-19 pandemic, we examined and compared trends in pediatric and adult intentional self-poisoning with acetaminophen, aspirin, ibuprofen, and naproxen from 2016 to 2021 using the National Poison Data System (NPDS) to see if these trends have continued. We extracted annual case counts of all suspected suicide attempts from intentional poisoning, and of suspected suicide attempts resulting in major effects or death, from the NPDS for non-prescription single ingredient adult formulation acetaminophen, non-prescription single ingredient adult formulation aspirin, single ingredient formulation ibuprofen, and single ingredient formulation naproxen. We enumerated the cases by year, age, and gender. Most cases of intentional self-poisoning within the review period involved acetaminophen and ibuprofen and the 13-19-year-olds constituted the highest proportion of intentional self-poisoning cases across age groups for all four analgesics. Cases involving females predominated cases involving males by 3:1 or greater. The 13-19-year-old age group also represented the largest proportion of cases that resulted in major clinical effects or deaths. An increasing trend in suicide poisoning cases with acetaminophen and ibuprofen was observed in the 6-19-years age group and this trend appeared to exacerbate from 2020 to 2021 corresponding with the start of the COVID-19 pandemic period.

Synthesis, Characterization and Molecular Docking of New Nucleosides and Schiff Bases Derived from Ampyrone as Antiviral Agents to Contain the COVID-19 Virus

A new series of nucleoside derivatives was prepared from the reaction of 4-aminoantipyrene with different sugar moieties. In addition, ampyrone's reaction with different aromatic aldehydes gave the corresponding Schiff base derivatives, which were also synthesized. Both molecular docking and in vitro antiviral activities at different concentrations of different synthesized compounds against SARS-CoV-2 were screened. All newly synthesized compounds were characterized on the basis of IR, 1H NMR and 13C NMR spectral data and physical data. The compounds were screened for potential cytotoxic activities. The molecular docking analysis showed that compounds 6b, 6e, 6c, 6f and 6d exhibited relatively higher binding energies (−8.1, −8.1, −8.3, −8.4 and −8.7 kcal/mol, respectively) compared to all the other compounds. However, the different compounds did not show any promising in vitro antiviral activities against SARS-CoV-2.

Prolonged Cessation of Chronic Opioid Analgesic Therapy: A Multidisciplinary Intervention

Am J Manag Care. 2022;28(2):60-65. https://doi.org/10.37765/ajmc.2022.88785 _____ Takeaway Points Building on articles previously published in this journal, this research suggests a potential path toward an effective and sustained clinical approach to decrease chronic opioid analgesic therapy use in the population of patients with chronic, noncancer pain. * We retrospectively examine the initial and sustained success rates of full mu agonist chronic opioid analgesic therapy (COAT) cessation in the setting of chronic, noncancer pain (CNCP) through voluntary participation in a pilot program—implemented via 2 sites and care teams—that provided a standardized, multidisciplinary curriculum containing robust complementary care. * This study provides unusually lengthy follow-up for postintervention COAT cessation monitoring of up to 24 months. * Initial COAT cessation success rates were high, and sustained success at 6 months and beyond was even higher (90%, 95%, and 97%, respectively), indicating that the program curriculum may be an effective strategy for broader application for sustainable COAT cessation in the setting of CNCP. _____ A recent CDC report suggests that years of nationwide medical and managed care regulations to limit prescription opioid access, dose, and time exposure have had minimal positive impact on life expectancy in the United States.1 Despite the wide abandonment of opioid prescriptions by the medical community, opioid-related mortality and morbidity have continued to rise, a trajectory that has accelerated due to the COVID-19 pandemic.1-3 Aside from being a contributor to overdose-related death, full mu agonist chronic opioid analgesic therapy (COAT) has been shown to impede vocational and social return to function and to increase length of disability.1,3,4 Managed care charges for patients with opioid dependency are more than 550% higher than the average annual per-patient charge.5 Also, the population of "opioid refugees" is gaining numbers—patients who were made dependent upon opioids by recent, but now out-of-favor, prescribing practices for the management of chronic pain and are now abruptly unable to find a medical source for the same medications.6 This has moved many patients with chronic pain dependent upon opioids to drastic measures such as seeking new or multiple prescribers, emergency medical care, or even illicit opioid sources.7 The medical community has been trialing and comparing several approaches to combat the ineffective use of COAT for chronic, noncancer pain (CNCP). Some managed care institutions have attempted a model of coverage cessation for these medications, resulting in paradoxically increased costs as patients struggle to cope.3 Clinicians have reported varying levels of success to promote COAT cessation through outpatient weaning8-12 and single-modality approaches of cognitive behavioral therapy (CBT),13,14 acupuncture,10 interdisciplinary programing,15-24 and buprenorphine substitution.20,25-27 None of the data present a definitive, best-practice approach to the challenge of the opioid epidemic in the setting of chronic pain. Every activity was designed for home exercise and was led by a licensed or credentialed expert in that field, such as a physician, nurse practitioner, psychologist, licensed acupuncturist, physical therapist, or licensed physical therapy assistant. Because the PDMP is ubiquitous as a record of presence and volume of prescribed controlled substances in California, with few exceptions (see Discussion), lack of an entry in the PDMP was interpreted as that subject not using opioids.

Discharge medicine supply – would a different approach positively impact patient flow?

AimsIn March 2020, prior to the first national lockdown, as part of escalation planning for the COVID pandemic, clinical areas within the Children's Unit in our District General Hospital were repurposed. This was to increase the number of single rooms to meet stringent social distancing and isolation standards. As a result of this, the overall bed capacity within the unit was reduced. A UK government publication at the time concluded that children who had so far been infected with the SARs-CoV2 virus had mild, or no symptoms and were far less likely than adults to need medical intervention. However, at this very early stage, it acknowledged that there was a lack of good quality data.1 There was concern within the service that admissions for any indication would need to be accommodated in fewer beds, and in order to maximise patient flow, options to reduce length of stay were examined. One of the pinch points in the patient journey was identified as the waiting time for discharge medication supply via the hospital pharmacy, as there was no paediatric discharge lounge, and the pharmacy team were asked to look at alternative, ward-based medication supply options.MethodSeveral options were identified and implemented. Changes to the local Code of Practice were effected to allow-Selected labelled discharge (TTO) packs for commonly used inhalers, antibiotics and analgesics to be dispensed at ward level against an Immediate Discharge Letter (IDL) 24 hours a day (previously only an out of hours option)Hospital HBP forms to be used far more widely for supply, via a community pharmacyIn addition, a small selection of Patient Group Directives (PGDs) which had previously been successfully trialled in the children's department was expanded to include indications for other commonly used drugs. These were used alongside the nurse-led discharge pathway if medical staff were not immediately available to write a discharge prescription. In order to help staff stratify which discharge medication supply method was most appropriate, a simple algorithm was written and displayed on the wards. Supply through the hospital pharmacy remained an option if required. Regardless of which strategy was used, communication to the GP of medicines supplied was essential.ResultsThe impact of the new process was assessed as part of a Foundation Trainee Year Pharmacist Audit. The audit sought a subjective opinion from staff. The results of this audit showed that staff were using the discharge pathways regularly, thought the discharge process was faster without compromising safety and patient care, and was undertaken well within their scope of competency. Prescription tracker data showed the number of discharge prescriptions being dispensed in pharmacy more than halved. A concern had been that medicines supplied on discharge would not be well communicated to the GP, but a review of a random sample of electronically transmitted IDLs showed that medications supplied via these new processes were being documented.ConclusionDischarge medicines can be supplied safely and without delay at ward level, or via Hospital community pharmacy prescriptions, if the correct processes are implemented and followed.ReferenceScientific Advisory Group for Emergencies. PHE-SARS CoV-2, SARS-CoV1 and MERS-CoV What do we know about children. 9 March 2020 – Updated 13 May 2022, https://www.gov.uk/government/publications/phe-sars-cov-2-sars-cov-1-and-mers-cov-what-do-we-know-about-children-9-march-2020a [Accessed 13 June 2022]

Patterns of Self-medication During the COVID-19 Pandemic in a Colombian population.

Introduction: Self-medication is considered one of the most relevant problems for public health, since it is described as the voluntary use of drugs by the patient. Since the beginning of the health crisis caused by the COVID-19 pandemic, it has been evident that this practice has increased considerably, especially in the adult population. Objective(s): To evaluate the different patterns that influence self-medication during the COVID-19 pandemic. Method(s): A survey was conducted among the population of two vicinities of Bogota and the statistical program SPSS was used for data analysis to identify the main practices that increase the risks derived from self-medication, the most used drugs and their adverse effects. Socioeconomic factors related to self-medication were evaluated. A comparative study was carried out to observe their behavior before and during the pandemic. Additionally, the influence of the people who are part of the family and social environment on self-medication was evaluated. Result(s): The total number of surveys carried out was 301. The average age was 44.18 years. It was found that before the pandemic there was a higher frequency of self-medication of analgesics (49.1 %) and anti-influenza drugs (19.5 %), and during the pandemic it was of non-steroidal anti-inflammatory drugs (4.43 %), home remedies (6.69 %) and antibiotics (30.38 %). In addition, it was found that those who had the greatest influence on self-medication were family members (23.9 %), friends or acquaintances (17.3 %) and the pharmaceutical chemist (5.0 %). Conclusion(s): It is evident that during the COVID-19 pandemic self-medication is higher than in the pre-pandemic era, increasing the risk of adverse events and compromised patient safety.Copyright © 2023, Editorial Ciencias Medicas. All rights reserved.

Development of a multivariate model with desirability-based optimization for simultaneous determination of five co-administrated drugs for the management of COVID-19 infection in their dosage forms via validated RP-HPLC method

More than 2.9 million people have died as a result of the global demographic impact of the coronavirus illness of 2019 (COVID-19). Numerous antiviral and anti-inflammatory medications have FDA approval to treat COVID-19 patients. For the simultaneous determination of COVID-19 utilized medications (Remdesivir, Moxifloxacin, Dexamethasone, Apixaban, and paracetamol) in their dosage forms, a sensitive technique has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method's analytical parameters. It employed RP-HPLC with a UV detector. An INERTSIL ODS-3 C18 column (5 µm, 250 × 4.6 mm) with mobile phase composed of acetonitrile: 30 mmoL potassium dihydrogen phosphate buffer (pH = 7.5) (50:50, v/v), at room temperature was employed to separate the aforementioned drugs. Paracetamol was linear over the concentration range (1–50 µg/mL), Moxifloxacin (5–70 µg/mL), Apixaban (5–70 µg/mL), Dexamethasone (1–100 µg/mL), and Remdesivir (5–100 µg/mL). According to ICH guidelines, the new approach underwent thorough validation. Between the proposed method's results and those from the reference or reported methods, there was no significant difference. The technique is simple to use in research of the cited medications in their dosage forms for quality control aspects.

Chronic pain and continuity of analgesic treatment during the COVID-19 pandemic.

INTRODUCTION: Chronic pain can trigger both physical and mental health complications. During the COVID-19 pandemic, patients with chronic diseases have had reduced access to some medications. OBJECTIVE: To determine the pharmacological management of patients with chronic pain and its continuity during the COVID-19 pandemic. METHODS: This was a retrospective longitudinal study of the continuity of analgesic use in patients with chronic pain between September 1, 2019 and February 28, 2021 based on a drug dispensing database. Survival analysis was performed until the discontinuation of chronic analgesics. RESULTS: A total of 12,701 patients who were being treated for chronic pain were identified. Their median age was 70.3 years, and 74.4% were women. The pain of rheumatological origin was the most frequent etiology (46.1%); the most used medications were nonopioid analgesics (78.9%), pain modulators (24.8%) and opioid analgesics (23.3%). A total of 76.1% of the patients experienced interruptions in their management during the study period. The median time to the first interruption of treatment was 5.0 months (95% CI: 4.8-5.2). Those who were treated for oncological pain experienced a greater number of interruptions in their management. CONCLUSIONS: The pharmacological management of patients with chronic pain is heterogeneous, and this real-world study showed that a high proportion of patients experienced an interruption of pain management during the 12 months following the onset of the COVID-19 pandemic.

Reviews of articles on medicinal herbs

Efficacy and safety of ginger on the side effects of chemotherapy in breast cancer patients: systematic review and meta-analysis. Based on these studies, the authors undertook a systemic review and meta-analysis to assess the efficacy and safety of using ginger in the symptomatic management of chemotherapy side effects in breast cancer patients. [...]more large, highquality RCTs using uniform methodology are required to evaluate ginger's safety and efficacy in this population. [...]the current study assessed the potential of E. purpurea in preventing and treating respiratory tract infections (RTIs) in people with respiratory viral infections, including SARS-CoV-2.

Frequency of Inactivated COVID-19 Vaccine Side Effects in a Tertiary Care Hospital of Karachi

Objective: to determine the frequency of the possible side effects of the COVID-19 inactivated vaccine. Study Design: Cross-sectional survey. Place and Duration of Study: Pakistan Naval Ship Shifa Hospital, Karachi Pakistan from Jan to Apr 2021. Methodology: A total of 305 recipients of inactivated COVID-19 vaccine were asked to fill out a questionnaire themselves or by the health care worker via telephonic conversation. The questionnaire comprised queries regarding general and local side effects that the participants experienced after getting vaccinated for COVID-19. Results: Out of 305 recipients, 270(88.5%) were men, and 35(11.5%) were women. Participants' age ranged from 18-60 years. After the first dose, 83(27.2%) cases [male 63(23.3%) vs. female 20(57.1%)], were reported with side effects, while 75(24.5%) recipients, [male: 54(19.9%) vs. female: 21(58.8%)], had side effects after the second dose. Generalized symptoms were fever, headache, dizziness, and body aches, while local side effects were pain, itching, swelling and rash at the injection site. 259(84.9%) recipients reported spontaneous recovery after the first dose. After the second dose, 286(93.8%) recipients recovered spontaneously. The remaining 44(13%) of the recipients' required symptomatic treatment. After the second dose, only 19(6%) recipients needed symptomatic treatment. Conclusion: It is important to document the possible side effects of COVID vaccine so that public awareness and education can be made to minimize public fear of vaccine side effects. Inactivated vaccine for COVID-19 has minimal reported side effects and hence has a good safety profile.

Photocatalytic Degradation of Paracetamol under Simulated Sunlight by Four TiO2 Commercial Powders: An Insight into the Performance of Two Sub-Micrometric Anatase and Rutile Powders and a Nanometric Brookite Powder

The photocatalytic degradation of the emerging contaminant paracetamol in aqueous solution has been studied under 1 SUN (~1000 W m−2) in the presence of four commercial TiO2 powders, namely sub-micrometric anatase and rutile, and nanometric brookite and P25 (the popular anatase/rutile mixture used as a benchmark in most papers). The rutile powder showed low activity, whereas, interestingly, the anatase and the brookite powders outperformed P25 in terms of total paracetamol conversion to carboxylic acids, which, according to the literature, are the final products of its degradation. To explain such results, the physicochemical properties of the powders were studied by applying a multi-technique approach. Among the physicochemical properties usually affecting the photocatalytic performance of TiO2, the presence of some surface impurities likely deriving from K3PO4 (used as crystallization agent) was found to significantly affect the percentage of paracetamol degradation obtained with the sub-micrometric anatase powder. To confirm the role of phosphate, a sample of anatase, obtained by a lab synthesis procedure and having a "clean” surface, was used as a control, though characterized by nanometric particles and higher surface area. The sample was less active than the commercial anatase, but it was more active after impregnation with K3PO4. Conversely, the presence of Cl at the surface of the rutile did not sizably affect the (overall poor) photocatalytic activity of the powder. The remarkable photocatalytic activity of the brookite nanometric powder was ascribed to a combination of several physicochemical properties, including its band structure and nanoparticles size.

Worker Shortage, Pandemic Make Drug Diversion Easier

The article offers information on how problem of drug diversion among healthcare workers is exacerbated by lax reporting systems and hospital disincentives to alert patients and raise liability issues. Topics include how diverters can move to other facilities and avoid oversight by medical and nursing boards;how covid-19 pandemic has made drug diversion investigations harder to fund;and how longstanding problem often results in a multivictim crime after an outbreak.

Trends in pediatric nonprescription analgesic/antipyretic exposures during the COVID-19 pandemic.

OBJECTIVE: To examine pediatric exposure trends involving selected nonprescription analgesics/antipyretics, before and during the COVID-19 pandemic. METHODS: Using descriptive and interrupted time-series analyses, we assessed monthly United States poison center data involving pediatric (<18 years) exposures to nonprescription paracetamol (acetaminophen), ibuprofen, acetylsalicylic acid, and naproxen before (January 2015-February 2020) and during (March 2020-April 2021) the pandemic. Statins and proton pump inhibitors (prescription or nonprescription) served as controls. RESULTS: Most nonprescription analgesic/antipyretic exposures (75-90%) were single-substance; unintentional exposures typically involved children <6 years (84-92%), while intentional exposures involved females (82-85%) and adolescents, 13-17 years (91-93%). Unintentional exposures among children <6 years, declined for all four analgesics/antipyretics immediately after the World Health Organization declared COVID-19 a pandemic (March 11, 2020), but most significantly for ibuprofen (30-39%). Most intentional exposures were classified as suspected suicide. Intentional exposures were relatively low and stable among males. Intentional exposures in females declined immediately after the pandemic was announced but subsequently increased to pre-pandemic levels for acetylsalicylic acid and naproxen and above pre-pandemic levels for paracetamol and ibuprofen. For paracetamol, female intentional exposures increased from 513 average monthly cases in the pre-pandemic to 641 average monthly cases during the pandemic; and reached 888 cases by the end of the study period in April 2021. While for ibuprofen, average monthly cases rose from 194 in the pre-pandemic, to 223 during the pandemic; and reached 352 cases in April 2021. Patterns were similar among females 6-12 and 13-17 years. CONCLUSION: Nonprescription analgesic/antipyretic unintentional exposure cases declined among young children, while intentional exposure cases increased among females, 6-17 years, during the pandemic. Findings highlight the importance of safely storing medications and being alert to signs that adolescents may be in need of mental health support services; caregivers should seek medical care or call poison control centers for any suspected poisoning event.

The occurrence of emerging compounds in real urban wastewater before and after the COVID-19 pandemic in Cali, Colombia.

The COVID-19 pandemic is considered one of the most significant global disasters in the last years. The rapid increase in infections, deaths, treatment, and the vaccination process has resulted in the excessive use of pharmaceuticals that have entered the environment as micropollutants. Considering the prior information about the presence of pharmaceuticals found in the wastewater of Cali, Colombia, which was collected from 2015 to 2022. The data monitored after the COVID-19 pandemic showed an increase in the concentration of analgesics and anti-inflammatory drugs of up to 91%. This increase was associated with the consumption of pharmaceuticals for mild symptoms, such as fever and pain. Moreover, the increase in concentration of pharmaceuticals poses a highly ecological threat, which was up to 14 times higher than that reported before of COVID-19 pandemic. These results showed that the COVID-19 had not only impacted human health but also had an effect on environmental health.

De-implementing opioid prescribing in a dental group practice: Lessons learned.

BACKGROUND: Drug overdose has become a leading cause of accidental death in the United States. Between 2000 and 2015, the rate of deaths from drug overdoses increased 137%, including a 200% increase in the rate of overdose deaths involving opioids (including opioid pain relievers and heroin). Unnecessary opioid prescribing is one of the factors driving this epidemic. OBJECTIVES: The primary objective of this paper is to share lessons learned while conducting a randomized trial to de-implement opioids for post-extraction pain management utilizing clinical decision support (CDS) with and without patient education. The lessons learned from conducting this trial in a real-world setting can be applied to future dissemination and implementation oral health research. METHODS: The sources informing lessons learned were generated from qualitative interviews conducted with 20 of the forty-nine dental providers involved in the study following the implementation phase of the trial. Ongoing policy, social and environmental factors were tracked throughout the study. RESULTS: Dental providers in the trial identified the impact of training that involved health professionals sharing information about the personal impact of pain and opioid use. Additionally, they found utility in being presented with a dashboard detailing their prescribing patterns related to other dentists. For the 30 general dentists with access to the CDS, use of its portal varied widely, with most using it 10%-49% of the time related to extractions. CONCLUSIONS: In the context of a downward trend in opioid prescribing and considering the influence of the COVID pandemic during the trial, dental providers indicated benefit in training about negative personal impacts of prescribing opioids, and personally relevant feedback about their prescribing patterns. Only modest use of the CDS was realized. Implementation of this trial was impacted by governmental and health system policies and the COVID pandemic, prompt the consideration of implications regarding continuing ways to limit opioid prescribing among dental providers.

Adverse drugs reactions to paracetamol and ibuprofen in children: a 5-year report from a pediatric poison control center in Italy.

BACKGROUND: This study aimed to analyze all the patients who contacted the hospital's pediatric poison control center (PPCC) for exposure to ibuprofen and acetaminophen, in order to assess the incidence of any adverse reactions. METHODS: We retrospectively reported the clinical data of children who accessed the PPCC of the Bambino Gesù Children's Hospital, IRCCS, Rome, from January 1, 2018 to September 30, 2022 due to wrong, accidental or intentional intake of inappropriate doses of acetaminophen and/or ibuprofen. In addition, we compared patients according to the intake of one of the two drugs and reported the trimestral distribution of cases during the study period. RESULTS: A total of 351 patients accessed the PPCC during the study period. The median age was 3.0 years. Most patients were females (57.8%). The most common reason for inappropriate oral intake of paracetamol or ibuprofen was a wrong use or an accidental intake (78.6%), with a fifth of patients taking the drug with suicidal intent (21.1%). According to the PPCC evaluation, most patients were not intoxicated (70.4%). Hospitalization was required for 30.5% of patients. Adverse reactions were reported in 10.5% of cases, with a similar incidence in patients who took paracetamol or ibuprofen. Nausea and vomiting were the most commonly reported adverse reactions. A higher frequency of moderate intoxication was found in patients who took paracetamol compared to ibuprofen (p = 0.001). The likelihood of intoxication was also higher in the paracetamol cohort. A spike of cases was registered at the end of 2021. CONCLUSIONS: We analyze exposures to the two most commonly used pediatric molecules, paracetamol and ibuprofen, to assess the frequency of adverse reactions. We demonstrated that these relatively "safe" drugs may be associated with intoxications and adverse reactions when inappropriately administered.

Lessons from the implementation of a trauma center-based program to support primary care providers in managing opioids and pain after trauma hospitalization.

Background: Decreasing exposure to prescription opioids is critical to lowering risk of opioid misuse, overdose and opioid use disorder. This study reports a secondary analysis of a randomized controlled trial implementing an opioid taper support program directed to primary care providers (PCPs) of patients discharged from a level I trauma center to their homes distant from the center, and shares lessons for trauma centers in supporting these patients. Methods: This longitudinal descriptive mixed-methods study uses quantitative/qualitative data from trial intervention arm patients to examine implementation challenges and outcomes: adoption, acceptability, appropriateness, feasibility, fidelity. In the intervention, a physician assistant (PA) contacted patients after discharge to review their discharge instructions and pain management plan, confirm their PCP's identity and encourage PCP follow-up. The PA reached out to the PCP to review the discharge instructions and offer ongoing opioid taper and pain management support. Results: The PA reached 32 of 37 patients randomized to the program. Of these 32, 81% discussed topics not targeted by the intervention (eg, social/financial). The PA identified and reached a PCP's office for only 51% of patients. Of these, all PCP offices (100% adoption) received one to four consults (mean 1.9) per patient (fidelity). Few consults were with PCPs (22%); most were with medical assistants (56%) or nurses (22%). The PA reported that it was not routinely clear to patients or PCPs who was responsible for post-trauma care and opioid taper, and what the taper instructions were. Conclusions: This level I trauma center successfully implemented a telephonic opioid taper support program during COVID-19 but adapted the program to allow nurses and medical assistants to receive it. This study demonstrates a critical need to improve care transition from hospitalization to home for patients discharged after trauma. Level of evidence: Level IV.