Food Chem Toxicol. 2023 Feb;172:113598. doi: 10.1016/j.fct.2022.113598. Epub 2023 Jan 3.

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications that are routinely been used across the world. Their analgesic, anti-inflammatory, and antipyretic effects have all been well-documented. Moreover, they are been deliberated to have a protective role against various critical diseases such as cancer and cardiovascular diseases. However, the data presented by numerous studies in past have signified the adverse effects of NSAIDs due to overdosing on various systems such as cardiovascular, gastrointestinal, hepatic, renal, neural, etc. Despite substantial studies representing the mechanism behind the clinical risk of NSAIDs, there are very few reviews that have collated comprehensive records of various toxicities caused by overdosing on NSAIDs. As a result, we have presented a comprehensive overview of existing information on NSAIDs in this review. In addition to that, we have concentrated on presenting our understanding of various organ-based toxicities caused due to NSAID's prolonged use/overdosage.

PMID:36608735 | DOI:10.1016/j.fct.2022.113598

Phytomedicine. 2023 Jan;109:154535. doi: 10.1016/j.phymed.2022.154535. Epub 2022 Nov 9.

ABSTRACT

BACKGROUND: The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored.

OBJECTIVE: To evaluate the safety of NDQG in kidney disease treatment.

METHODS: The literature was searched in Embase, Medline via PubMed, Cochrane Library database, Wanfang database, Chinese National Knowledge Infrastructure, SinoMed, and Chinese VIP Database from inception to January 15, 2022, for randomized controlled trials (RCTs) and observational studies. The ClinicalTrials.gov website was searched for ongoing trials. The frequency and characteristics of adverse drug reactions (ADRs) were the primary and secondary outcomes, respectively. Subgroup analysis were conducted to explore the effects of clinical trial types, different kidney diseases, drug combinations and dosage on the safety of NDQG.

RESULTS: This review included 132 trials comprising 115 RCTs and 17 cohort studies. Additionally, 118 studies reported ADR rates with complete data, including 10381 participants. Regarding ADR frequency, no significant difference was observed between NDQG (7.26%) and control (8.39%) groups (RR = 0.890, 95% confidence interval (CI): 0.788-1.007); with no heterogeneity among the studies (I2 = 0.0%, P = 0.958). ADR frequency in patients with chronic kidney disease (65 trials, n = 5823) was significantly lower in the NDQG treatment group than in the control group (RR = 0.810, 95% CI: 0.67-0.969, I2 = 0.0%, P = 0.993); however, for patients with diabetic nephropathy there was no difference between both groups (26 trials, n = 2166, RR = 1.077, 95% CI: 0.802-1.446, I2 = 0.0%, P = 0.611). Similarly, the incidence of ADR in patients on dialysis and patients with pyelonephritis and nephrotic syndrome was the same for both groups, with 95% CI overlapping the line. For different interventions, including NDQG monotherapy or its combination with other commonly used drugs (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin drugs, and compound α-keto acid) or dialysis, the incidence of ADR showed no significant difference between the experimental and control arms. The ADR in the NDQG group primarily affected the gastrointestinal system (64.74%), central and peripheral nervous system (9.07%), whole body (5.79%), and skin and appendages (4.53%). The most common clinical manifestations were diarrhea, nausea, and vomiting.

CONCLUSIONS: Our meta-analysis showed that compared with supportive therapy, the incidence of ADR was similar when NDQG was added. However, current evidence is not definitive and more well-designed and conducted RCTs are warranted to definitively establish the reliable evidence.

PROTOCOL REGISTRATION NUMBER: PROSPERO CRD 42018104227.

PMID:36610168 | DOI:10.1016/j.phymed.2022.154535

J Pharm Pharm Sci. 2022;25:377-390. doi: 10.18433/jpps33020.

ABSTRACT

PURPOSE: Vemurafenib received approval for treatment of BRAF V600 variation metastatic melanoma in August 2011. This study analyzed Vemurafenib-related adverse events (AEs) to detect and characterize relevant safety signals using the real-word-data through the Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the healthcare products regulatory agency (MHRA), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms, were applied to quantify the signals of vemurafenib-related AEs.

RESULTS: Out of 8,042,244 reports gathered from the FAERS, 9554 reports of vemurafenib as the 'primary suspected (PS)' AEs were recognized. Vemurafenib-induced AEs occurrence targeted 23 system organ class (SOC). A total of 138 significant disproportionality PTs was simultaneously reserved according to the four algorithms. Unexpected significant AEs such as sarcoidosis and kidney fibrosis might also occur. The median onset time of vemurafenib-related AEs was 26 days (interquartile range [IQR] 8-97 days), and most of the cases occurred within the first one and two months after vemurafenib initiation.

CONCLUSION: Our study detected potential new AEs signals and might provide powerful support for clinical monitoring and risk identification of vemurafenib.

PMID:36608646 | DOI:10.18433/jpps33020

J Pharm Pharm Sci. 2022;25:369-376. doi: 10.18433/jpps33001.

ABSTRACT

PURPOSE: Osteoporosis is an adverse event of prednisolone. This study aimed to assess prednisolone-induced osteoporosis (PIO) profiles and patient backgrounds by analyzing data from the Japanese Adverse Drug Event Report (JADER) database.

METHODS: The current study focused only on orally administered prednisolone. PIO was defined using preferred terms from the Medical Dictionary for Regulatory Activities. Reporting odds ratio (ROR) at 95% confidence interval (CI) and the time-to-onset profile of PIO were used to evaluate adverse events.

RESULTS: The RORs (95% CI) of the female and male subgroups were 4.73 (4.17-5.38) and 2.49 (2.06-3.00), respectively. The analysis of time-to-onset profiles demonstrated that the median values (interquartile range: 25.0-75.0%) of PIO were 136 (74.0-294.0). The prednisolone treatment duration was significantly longer in the PIO patient group than in the non-PIO patient group. The findings suggest that patients with rheumatoid arthritis, systemic lupus erythematosus, and nephrotic syndrome receiving prednisolone have different age-related PIO profiles.

CONCLUSIONS: Our results suggest that longer prednisolone treatment duration and larger cumulative dose might be risk factors of PIO. The potential risk for PIO should not be overlooked, and careful observation is recommended.

PMID:36608641 | DOI:10.18433/jpps33001

BMC Cancer. 2023 Jan 7;23(1):29. doi: 10.1186/s12885-023-10515-z.

ABSTRACT

PURPOSE: Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC.

METHODS: Between November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers.

RESULTS: Among the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. The ORR was 82.5%. 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10-0.79; P = 0.038). The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%).

CONCLUSION: It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study.

PMID:36611131 | DOI:10.1186/s12885-023-10515-z

J Perianesth Nurs. 2023 Jan 5:S1089-9472(22)00546-9. doi: 10.1016/j.jopan.2022.10.003. Online ahead of print.

ABSTRACT

PURPOSE: Postoperative sore throat (POST) is a frequent postoperative complication. Pre-induction budesonide inhalation is effective in POST prevention. However, it requires inhaler equipment and patient cooperation. Budesonide spraying on the endotracheal (ETT) cuff is simple and can be performed on most patients requiring endotracheal intubation. This study aims to compare the effects of budesonide spray and K-Y gel as an ETT cuff lubricant on the incidence and severity of POST.

DESIGN: Randomized and triple-blinded study.

METHODS: One hundred patients undergoing elective non-cardiac surgery were randomly allocated into the budesonide group (n = 50) and the K-Y gel group (n = 50). In the budesonide group, 200 mcg of budesonide was sprayed on the cuff of the ETT. For the K-Y gel group, the ETT cuff was lubricated with K-Y gel. A visual analog scale was used to assess the severity of POST at 2, 6, and 24 hours after surgery. Other complications of tracheal intubation and adverse effects of budesonide were also recorded.

FINDINGS: Compared to the K-Y gel group, the budesonide group had a significantly lower overall incidence of POST (30% versus 54%, P = .032) and reduced the risk of POST by 24% (relative risk reduction = 24%, 95% CI, 5.23-42.77, P = .012) as well as the incidence of hoarseness (8.6% vs 34%, P = .001) and cough (0% vs 8%, P = 0.041). No incidence of drug-related side effects was reported in both groups.

CONCLUSIONS: Spraying budesonide on the ETT cuff significantly reduces the incidence and severity of POST.

PMID:36610870 | DOI:10.1016/j.jopan.2022.10.003

Am J Med Sci. 2023 Jan 4:S0002-9629(22)00529-8. doi: 10.1016/j.amjms.2022.12.029. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that is associated with functional disability and reduced quality of life. The central pathology of RA is the inflammation of diarthrodial joints, but approximately 40% of patients experience extra-articular manifestations of RA. Extra-articular manifestations are complications of RA that constitute multisystem disorders, associated with genetic and environmental conditions, and increase mortality in RA patients. Observational studies of RA patients have suggested ethnic disparities exist for minority populations; however, less is known about the distribution and prevalence of RA complications and drug-related problems (DRPs). Our objective was to construct a disease profile of RA-related complications in the Hispanic Mexican-American population compared to the non-Hispanic population of El Paso, Texas.

METHODS: A retrospective study was conducted in a Texas Tech University Health Science Center El Paso from 2009 to 2019 to assess the prevalence of RA-related complications in the Hispanic vs non-Hispanic population. The primary parameters were RA diagnosis, serological status, RA-treatment modalities, and history of associated complications. Data were extracted by chart review and correlated to disease-related and treatment-related complications. STATA was used to perform statistical analyses. A p-value of < 0.05 determined statistical significance.

RESULTS: One thousand five hundred five (N=1505) patients, diagnosed with RA, were included in this study. Of the cohort, 82.52% of patients were females, 76.81% were Hispanic, and 64.12% had no smoking history. From the total cohort, seven hundred fifty-six (N=756) patients had documentation of serological markers (Rheumatoid factor (RF) and/or Anti-cyclic citrullinated peptide (Anti-CCP)); 78.44% of patients whose serological status was documented, were positive for RF and/or Anti-CCP. Multivariate regression analysis revealed Hispanics have 15% and 17% less risk of overall RA complications and drug-related side-effects, respectively, compared to non-Hispanics (p-value <0.0001). However, within the entire cohort, those with a family history of RA had a 44% more risk of complications compared to those without family history (p-value <0.0001). Additionally, modifiable risk factors, i.e., active smoking and alcohol use had a higher complication risk, 19% and 21%, respectively (p-value <0.0001). Significantly, all patients seropositive for RF, and/or anti-CCP had a lower prevalence of RA-related and drug-related complications. However, non-Hispanic patients seropositive for RF or anti-CCP had a higher prevalence of specific complications of RA and DRPs compared to Hispanic patients.

CONCLUSION: In our retrospective review, analysis of sociodemographic characteristics reveals that Hispanic patients paradoxically have less risk of disease-related and treatment-related complications compared to non-Hispanic populations in El Paso, Texas. Genetic predisposition, modifiable environment/lifestyle factors had a higher prevalence of RA complications, congruent with established studies. Further analysis reveals that seropositive RA-patients have decreased complication prevalence compared to seronegative cohorts.

PMID:36610489 | DOI:10.1016/j.amjms.2022.12.029

Cell Mol Life Sci. 2023 Jan 7;80(1):31. doi: 10.1007/s00018-022-04662-y.

ABSTRACT

BACKGROUND AND AIMS: Thiopurine-induced acute pancreatitis (TIP) is one of the most common adverse events among inflammatory bowel disease patients treated with azathioprine (AZA), representing a significant clinical burden. Previous studies focused on immune-mediated processes, however, the exact pathomechanism of TIP is essentially unclear.

METHODS: To model TIP in vivo, we triggered cerulein-induced experimental pancreatitis in mice receiving a daily oral dose of 1.5 mg/kg AZA. Also, freshly isolated mouse pancreatic cells were exposed to AZA ex vivo, and acinar cell viability, ductal and acinar Ca2+ signaling, ductal Cl- and HCO3- secretion, as well as cystic fibrosis transmembrane conductance regulator (CFTR) expression were assessed using microscopy techniques. Ras-related C3 botulinum toxin substrate (RAC1) activity was measured with a G-LISA assay. Super-resolution microscopy was used to determine protein colocalization.

RESULTS: We demonstrated that AZA treatment increases tissue damage in the early phase of cerulein-induced pancreatitis in vivo. Also, both per os and ex vivo AZA exposure impaired pancreatic fluid and ductal HCO3- and Cl- secretion, but did not affect acinar cells. Furthermore, ex vivo AZA exposure also inhibited RAC1 activity in ductal cells leading to decreased co-localization of CFTR and the anchor protein ezrin, resulting in impaired plasma membrane localization of CFTR.

CONCLUSIONS: AZA impaired the ductal HCO3- and Cl- secretion through the inhibition of RAC1 activity leading to diminished ezrin-CFTR interaction and disturbed apical plasma membrane expression of CFTR. We report a novel direct toxic effect of AZA on pancreatic ductal cells and suggest that the restoration of ductal function might help to prevent TIP in the future.

PMID:36609875 | DOI:10.1007/s00018-022-04662-y

Am J Ther. 2023 Jan-Feb 01;30(1):e93. doi: 10.1097/MJT.0000000000001595.

NO ABSTRACT

PMID:36608076 | DOI:10.1097/MJT.0000000000001595

PLoS One. 2023 Jan 6;18(1):e0279928. doi: 10.1371/journal.pone.0279928. eCollection 2023.

ABSTRACT

BACKGROUND: Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI.

METHODS: We utilized correlation-based network analysis (CNA) to investigate the relationship between medications or their combinations with AKI in a large cohort of critically ill patients in a tertiary medical center between 2007 and 2018. Pairwise medication-AKI correlation analysis was performed to evaluate drug synergistic or additive effects. To investigate the inherent nephrotoxicity of medications, we further analyzed medications that were not paired with any other medications within 24 hours before or after their administration time (isolated medication analysis).

RESULTS: Among 147,289 ICU admissions, we identified 244 associations among 1,555 unique medication types. In pairwise analysis, 233 significant correlations were found among 13,150,198 medication pair instances. In isolated medication analysis, ten significant AKI associations were noted. When stratified by eGFR level, substantial differences between eGFR<90 vs. eGFR≥90 patients were observed. This highlights a need to determine eGFR as a risk factor for nephrotoxicity assessment when drug interactions are considered.

CONCLUSIONS: This large-scale cohort study identified an artificial intelligence model to identify patient-agnostic relationships between medication or their pairs with AKI incidence among critically ill patients. It could be used as a continuous quality assurance tool to monitor drug-associated risk nephrotoxicity.

PMID:36607965 | PMC:PMC9821414 | DOI:10.1371/journal.pone.0279928

Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(23):6297-6307. doi: 10.19540/j.cnki.cjcmm.20220725.501.

ABSTRACT

Although targeted therapy and immunotherapy will become the trend of systematic therapy for tumor in the future, radiotherapy and chemotherapy are still regarded as one of the main means to treat cancer due to their low price and wide application. The toxic and side effects of radiotherapy and chemotherapy can limit the therapeutic effect and affect the body immunity, which is very difficult to deal with by modern medical means, and in this process, patients are prone to develop resistance to the application of radiotherapy and chemotherapy, which makes it difficult to implement follow-up treatment, leading to disease progression and ultimately affecting the prognosis of patients. In recent years, a large number of traditional Chinese medicine(TCM)-related clinical studies have found that classical prescriptions and non-classical prescriptions can markedly alleviate the toxic and side effects caused by radiotherapy and chemotherapy, with clear and significant efficacy, and to some extent, they can improve the quality of life and prolong the survival period of patients. Therefore, TCM decoction may provide new opportunities for intervening in the refractory and high-incidence toxic and side effects. To further explore the application of classical prescriptions and non-classical prescriptions in tumor, this study reviewed the mechanism of toxic and side effects caused by radiotherapy and chemotherapy, the mechanism of classical prescriptions and non-classical prescriptions in the treatment of toxic and side effects, and the classical prescriptions and non-classical prescriptions used for treating common toxic and side effects in recent five years. This study was expected to promote the application and development of classical prescriptions and non-classical prescriptions in the field of cancer treatment by systematically summarizing their research progress in the prevention and treatment of toxic and side effects caused by radiotherapy and chemotherapy.

PMID:36604874 | DOI:10.19540/j.cnki.cjcmm.20220725.501

Medicine (Baltimore). 2023 Jan 6;102(1):e32475. doi: 10.1097/MD.0000000000032475.

ABSTRACT

RATIONALE: Drug-induced aseptic meningitis (DIAM) is an uncommon meningitis and trimethoprim with or without sulfamethoxazole is the most involved antibiotic. Although DIAM is easily treated with the discontinuation of the causative drug, the diagnosis is a big challenge for physicians, as it remains a diagnosis of exclusion. Here, we present a case report of trimethoprim-sulfamethoxazole induced aseptic meningitis in a woman with acute osteomyelitis.

PATIENT CONCERNS: A 52-year-old woman was admitted to the hospital for septic shock and acute osteomyelitis of the right homerus. She was started on antibiotic therapy with oxacillin and daptomycin, then oxacillin was replaced with cotrimoxazole, due to its excellent tissue penetration, including bone tissue. During cotrimoxazole therapy, the patient developed a fluent aphasia with ideomotor apraxia and muscle hypertonus.

DIAGNOSIS AND INTERVENTIONS: Having excluded infectious, epileptic and vascular causes of the acute neurologic syndrome of our patient, given the improvement and full recovery after discontinuation of cotrimoxazole, we hypothesized a DIAM.

OUTCOMES: After discontinuation of cotrimoxazole, in 48 hours the patient had a full recovery.

LESSONS: Although DIAM can be easily managed with the withdrawal of the causative drug, it can be difficult to recognize if it is not included in the differential diagnosis. An antimicrobial stewardship program with a strict monitoring of patients by infectious disease specialists is essential, not only to optimize the appropriate use of antimicrobials, but also to improve patient outcomes and reduce the likelihood of adverse events.

PMID:36607874 | DOI:10.1097/MD.0000000000032475

Front Oncol. 2022 Dec 20;12:1070001. doi: 10.3389/fonc.2022.1070001. eCollection 2022.

ABSTRACT

PURPOSE: To compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®.

METHODS: A multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0-t and AUC0-∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over.

RESULTS: 48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0-t and AUC0-∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®.

CONCLUSIONS: Bioequivalence between the test and the reference products was established for free and encapsulated doxorubicin.

CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn, identifier [CTR20210375].

PMID:36605440 | PMC:PMC9810385 | DOI:10.3389/fonc.2022.1070001

Cureus. 2022 Dec 4;14(12):e32174. doi: 10.7759/cureus.32174. eCollection 2022 Dec.

ABSTRACT

Entrectinib is a recently approved multikinase inhibitor to treat advanced c-ros oncogene1 (ROS1) positive non-small cell lung cancer (NSCLC). Although molecular targeted therapy is generally well tolerated, cardiovascular adverse events have been described in recent years. We report a case of NSCLC with ROS1 rearrangement where the patient developed drug-induced heart failure after receiving entrectinib. A 74-year-old non-smoker female patient was diagnosed with stage IVB lung adenocarcinoma with ROS-1 positive and right breast cancer stage I. We started on entrectinib as the first-line therapy for lung cancer. Five days after, she developed oral dysesthesia and blood creatinine increased. These findings gradually worsened, so we temporarily discontinued entrectinib. After withholding the drug for 14 days, these findings improved, and we resumed entrectinib at a reduced dose. On day 19 of the reduced entrectinib dose, she presented to the outpatient with shortness of breath and bilateral lower extremity edema, accompanied by respiratory failure. Laboratory evaluation revealed elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), troponin I, creatine kinase (CK), and C reactive protein (CRP), and transthoracic echocardiogram showed congestive heart failure (CHF) with a preserved ejection fraction (HFpEF). She did not complain of chest pain and fever, so we did not consider ischemic heart disease and viral myocarditis in the initial evaluation. There was no other causative cause of CHF. Therefore, we suspected entrectinib-related heart failure. Her symptoms improved and she recovered her cardiac function to baseline within a week of discontinuation of entrectinib and standard heart failure treatment. She developed heart failure after a one-step dose reduction and was prone to cardiotoxicity due to entrectinib. Considering that she could be treated with crizotinib, we decided discontinuation of entrectinib permanently. This case report highlights the potential cardiotoxicity of entrectinib and suggests the need for close monitoring of the cardiac functions of patients receiving entrectinib.

PMID:36605067 | PMC:PMC9808486 | DOI:10.7759/cureus.32174

Endocrinol Metab (Seoul). 2022 Dec;37(6):839-850. doi: 10.3803/EnM.2022.1627. Epub 2022 Dec 26.

ABSTRACT

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

PMID:36604955 | DOI:10.3803/EnM.2022.1627

BMC Infect Dis. 2023 Jan 5;23(1):5. doi: 10.1186/s12879-022-07974-3.

ABSTRACT

BACKGROUND: The Pfizer BioNTech COVID-19 vaccine was the first to receive emergency authorization and approval from the FDA. Therefore, it is preferred by most recipients; however, many people are concerned about the vaccine's side effects. At the time of the study, December 2021, Palestine lacked a national reporting system for monitoring adverse vaccine effects. Therefore, this study investigates the post-vaccine adverse events following the Pfizer/BioNTech COVID-19 Vaccine administration in Palestine and identifies the occurrence, extent, and severity among university staff, employees, and students at Birzeit University.

METHOD: A questionnaire-based retrospective cross-sectional study was conducted using a university website (Ritaj), social media platforms (e.g., Facebook and Telegram), and in-person interviews. The Chi-square, Fisher's exact, and McNemar's tests were used to investigate significant relationships. Data were analyzed using SPSS version 22.

RESULTS: In total, 1137 participants completed the questionnaire, 33.2% were males, and the mean age was 21.163 years. All participants received at least one dose of the Pfizer-BioNTech COVID-19 vaccine. Approximately one-third of participants reported no adverse effects after receiving the first, second, or third doses (34%, 33.6%, and 32.5%, respectively). The most commonly reported adverse events were fever, chills, headache, fatigue, pain and swelling at the injection site, muscle pain, and joint pain. Allergic reactions were reported by 12.7% of the participants; furthermore, participants with a history of allergy or anaphylaxis before vaccination had a significantly higher tendency for post-vaccination allergic reactions. Eight participants reported rare side effects, including 7 (0.6%) cases of thrombocytopenia and one (0.1%) case of myocarditis. Males aged less than 20 years and smokers were significantly less likely to complain of adverse events. The number of reported side effects was significantly higher after the second vaccine dose than after the first dose. Finally, participants infected with COVID-19 before vaccination was significantly associated with side effects such as fever, chills, shortness of breath, and persistent cough.

CONCLUSION: In this study, the most common post- BNT162b2 Vaccination reported self-limiting side effects similar to those reported by Pfizer/BioNTech Company. However, higher rates of allergic reactions were reported in this sample. Rare side effects, such as thrombocytopenia and myocarditis, were reported by 8 participants. COVID vaccines have been developed at an accelerated pace, and vaccine safety is a top priority; therefore, standard monitoring through a national adverse event reporting system is necessary for safety assurance. Continuous monitoring and long-term studies are required to ensure vaccine safety.

PMID:36604613 | PMC:PMC9814351 | DOI:10.1186/s12879-022-07974-3

JAMA Netw Open. 2023 Jan 3;6(1):e2244975. doi: 10.1001/jamanetworkopen.2022.44975.

ABSTRACT

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) causes severe inflammation of multiple organ systems after SARS-CoV-2 infection. During the pandemic, surveillance reporting of MIS-C was voluntary, with likely underreporting. For a rare syndrome like MIS-C, numerous data are needed to explore the disease in greater detail.

OBJECTIVE: To use large all-payer billing data and the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) code for MIS-C to compare outcomes across MIS-C and COVID-19 over all 4057 hospitals in 31 states.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cross-sectional study of all COVID-19 and MIS-C hospitalizations in individuals younger than 21 years from 31 states was conducted, using Agency for Healthcare Research and Quality 2021 Healthcare Cost and Utilization Project data. Analyses were conducted from February 1 to October 20, 2022.

MAIN OUTCOMES AND MEASURES: Fifty complications, adverse medication events, costs, and the Social Vulnerability Index.

RESULTS: There were 4107 individuals with MIS-C (median age, 9 [IQR, 5-13] years; 2443 [59.5%] male; 1384 [38.1%] White) and 23 686 individuals with COVID-19 without MIS-C (median age, 15 [IQR, 5-18] years; 12 878 [54.4%] female; 4605 [44.1%] White), with 1.48 (95% CI, 1.35-1.62) MIS-C hospitalizations per 100 000 children per month, ranging from 0.97 hospitalizations per 100 children for White and 1.99 hospitalizations per 100 children for Black children. Outcomes worsened as the number of organ system dysfunctions increased from 2 to 8 organs. Deaths associated with MIS-C increased from less than 1% to 5.8% (95% CI, 3.3%-8.4%) and from less than 1% to 17.2% (95% CI, 11.7%-22.7%) for COVID-19 (P = .001). Adverse medication events associated with MIS-C increased from 4.9% (95% CI, 3.8%-6.0%) to 17.8% (95% CI, 13.7%-22.0%) and from 1.2% (95% CI, 1.0%-1.3%) to 13.4% (95% CI, 8.4%-18.3%) for COVID-19. The median length of stay for MIS-C increased from 4 (IQR, 2-5) to 8 (IQR, 5-12) days and from 3 (IQR, 2-5) to 16 (IQR, 7-23) days for COVID-19. Median costs for MIS-C increased from $16 225 (IQR, $9244-$26 822) to $53 359 (IQR, $35 920-$86 882) and from $6474 (IQR, $3741-$12 103) to $98 643 (IQR, $30 675-$204 956) for COVID-19. The percentage of MIS-C cases that were in Black children doubled from 16.2% to 31.7% (P = .001) as organ dysfunction increased, remaining unchanged with COVID-19. Hospital stays for MIS-C increased by 1 day (P = .01) for Black patients compared with White patients, with Black patients moving from the bottom to top quartile of socioeconomic vulnerability, with no disparity with COVID-19.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, MIS-C was more common and severe than previously reported, with more racial disparities in outcomes than were seen in patients with COVID-19. The findings of this study suggest that relying on mean outcomes for MIS-C from past studies can be misleading, since outcomes and disparities varied widely with the number of multiorgan dysfunctions.

PMID:36602804 | DOI:10.1001/jamanetworkopen.2022.44975

Am J Case Rep. 2023 Jan 5;24:e938358. doi: 10.12659/AJCR.938358.

ABSTRACT

BACKGROUND Many drugs have been reported to cause immune-mediated adverse drug reactions (IM-ADRs) in human immunodeficiency virus (HIV) patients; the most common is cutaneous adverse drug reaction (CADR). Immune thrombocytopenia purpura (ITP) is frequent in HIV patients, and it can be caused HIV, opportunistic infections, or drugs. Although drugs can cause immune thrombocytopenia, termed drug-induced immune thrombocytopenia (DIIT), there has been no study on DIIT in HIV patients. CASE REPORT A 33-year-old male patient was admitted to our hospital with pruritic skin lesion over the entire body, which started 7 days before. He was diagnosed with HIV infection, brain toxoplasmosis, and pulmonary tuberculosis 2 weeks before admission, and was given trimethoprim sulphamethoxazole, isoniazid, rifampicin, pyrazinamide, and ethambutol. Clindamycin was added 10 days before admission. Skin examination revealed generalized erythematous macules with palpable petechiae and purpura. The platelet count was 141 000/µL when he was diagnosed with HIV, and it was 2000/µL at the time of admission. Clindamycin was discontinued and he was given steroids and platelet transfusion. The skin lesions improved along with an increased platelet count. He was discharged on the 10th day of admission, with platelet count of 42 000/µL. When he returned to the outpatient clinic on the 15th day, his platelet was 54 000/µL. The skin lesions had resolved completely and become hyperpigmented, and no purpura or petechiae were seen. CONCLUSIONS We present a case of an HIV patient with IM-ADR in the form of DIIT in conjunction with CADR that might have been caused by clindamycin.

PMID:36600572 | DOI:10.12659/AJCR.938358

Drug Ther Bull. 2023 Jan 5:dtb-2022-000076. doi: 10.1136/dtb.2022.000076. Online ahead of print.

ABSTRACT

Overview of: Suarez EA, Bateman BT, Hernández-Díaz S, et al Association of antidepressant useduring pregnancy with risk of neurodevelopmental disorders in children. JAMA Intern Med2022;182:1149-60.

PMID:36604159 | DOI:10.1136/dtb.2022.000076

Therap Adv Gastroenterol. 2022 Dec 26;15:17562848221142925. doi: 10.1177/17562848221142925. eCollection 2022.

ABSTRACT

BACKGROUND: A high-dose proton pump inhibitor (PPI)-amoxicillin dual therapy has been investigated for treatment of patients with Helicobacter pylori (H. pylori) infection. Currently, the efficacy of this dual therapy remains inconclusive, with controversial findings from various single-center clinical trials.

OBJECTIVES: To assess the efficacy and safety of high-dose dual therapy (HDDT) compared with the bismuth-containing quadruple therapy (BQT) in treatment-naive patients with H. pylori infection.

DESIGN: A multicenter, open-label, randomized controlled clinical trial.

METHODS: Three hundred and forty treatment-naïve patients with H. pylori infection were prospectively recruited from seven participating hospitals. The enrolled patients were randomized into one of two treatment groups: the HDDT group (esomeprazole, 20 mg four times daily; amoxicillin, 750 mg four times daily) and the BQT group (esomeprazole, 20 mg, twice daily; bismuth potassium citrate, 600 mg, twice daily; amoxicillin, 1 g, twice daily; metronidazole, 400 mg, four times daily). The primary outcome was eradication rate, and secondary outcomes were safety and patient compliance.

RESULTS: The eradication rates in the HDDT group versus the BQT group were 86.47% versus 87.06% on intention-to-treat (ITT) analysis, 91.88% versus 92.50% on modified ITT (MITT) analysis, and 91.77% versus 93.04% on per-protocol (PP) analysis, with no significant differences between the two groups. The patient compliance rates in the HDDT group versus the BQT group were 97.02% versus 95.86%, and no significant difference was found between the two groups. Notably, the HDDT group exhibited significantly lower incidence in the drug-induced adverse events (AEs) compared to the BQT group (16.67% versus 47.94%).

CONCLUSION: HDDT is equally efficacious in eradicating H. pylori infection and resulted in good patient compliance and safety compared with BQT. These findings provide evidence in support of HDDT as a first-line treatment for H. pylori infection.

REGISTRATION: This clinical trial was registered at The Chinese Clinical Trial Registry (trial registration number: ChiCTR2000039096).

PMID:36600686 | PMC:PMC9806404 | DOI:10.1177/17562848221142925