J Clin Transl Hepatol. 2023 Oct 28;11(5):1239-1245. doi: 10.14218/JCTH.2022.00067S. Epub 2023 Apr 28.

ABSTRACT

Drug-induced liver injury (DILI) is a major cause of acute liver injury, liver failure, and liver transplantation worldwide. In recent years, immune checkpoint inhibitors have become widely used. This has led to an increase in DILI, for which pathophysiology and management methods differ significantly from the past. As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase, information about a DILI is becoming more valuable. DILI is classified into two types according to its etiology: intrinsic DILI, in which the drug or its metabolites cause liver damage that is dose-dependent and predictable; and idiosyncratic DILI, in which liver damage is also dose-independent but unpredictable. In addition, depending on the course of the disease, chronic DILI or drug-induced autoimmune hepatitis may be present. The number of DILI cases caused by antimicrobial agents is decreasing, whereas that caused by drugs for malignant tumors and health foods is increasing. The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI. Liver injury is a type of immune-related adverse event. The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular, but mixed type and bile stasis have also been reported. Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury. Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration; however, mycophenolate mofetil may be considered if the disease is refractory to steroids.

PMID:37577239 | PMC:PMC10412691 | DOI:10.14218/JCTH.2022.00067S

Cureus. 2023 Jul 12;15(7):e41781. doi: 10.7759/cureus.41781. eCollection 2023 Jul.

ABSTRACT

Immune checkpoint inhibitors (ICIs) as standard of care have revolutionized the treatment of patients with metastatic melanoma. The combination of nivolumab and ipilimumab improves treatment efficacy and prolongs survival compared to monotherapy alone. However, combination therapy is also associated with an increased incidence of adverse events. We report an uncommon yet important case of multi-organ failure in a patient following a single dose of nivolumab plus ipilimumab. A 60-year-old male with a history of ulcerative colitis in remission and metastatic melanoma was admitted on February 25, 2021, for presumed sepsis, after presenting with neutropenic fever. His brain metastases were previously resected on January 14, 2021, and he was started on dexamethasone 4 mg BID for six weeks. On February 11, 2021, he received one dose of nivolumab plus ipilimumab, per the CheckMate-067 protocol. He presented 14 days later with fever, diarrhea, pancytopenia, renal failure, drug-induced hepatitis, and myocarditis. The infectious workup was negative. His neutropenia responded to growth factors. He was diagnosed with interstitial nephritis due to immunotherapy and treated with corticosteroids. His symptoms resolved with concomitant improvement of his renal, hepatic, and cardiac function. He was discharged home in a stable condition. Although these specific immune-related adverse events (irAEs) are uncommon and rarely occur simultaneously, ICIs can trigger non-specific immune system activation, resulting in widespread inflammatory effects. Since irAEs can lead to multi-organ failure, as evidenced in this case, early recognition and institution of high-dose steroids are critical to preventing rapid deterioration. Given that ICI therapy is the standard of care for several cancers and is often studied in clinical trials, increased education on irAE toxicity and updated algorithms on the management of febrile cancer patients are warranted.

PMID:37575835 | PMC:PMC10419328 | DOI:10.7759/cureus.41781

Cureus. 2023 Jul 10;15(7):e41647. doi: 10.7759/cureus.41647. eCollection 2023 Jul.

ABSTRACT

Introduction Multiple risk factors, such as human immunodeficiency virus (HIV) infection and immunosuppressive therapies, increase the odds of latent tuberculosis infection (LTBI) reactivation and progression to active tuberculosis. A six-to-nine-month preventive treatment with isoniazid (INH) decreases the risk of LTBI reactivation, but its effectiveness can be limited by its long duration and adverse events (AEs), including liver toxicity. Due to comorbidities and polypharmacy, people living with HIV (PLHIV) may be at increased risk of INH-associated AEs. Our study aimed to assess the prevalence of AEs among patients receiving INH treatment for LTBI, to identify risk factors for their occurrence, and to evaluate whether PLHIV have higher odds of developing INH-associated AEs. Methods We conducted a single-center retrospective case-control study, including 130 outpatients with LTBI treated with INH between July 2019 and March 2022. Participants who developed AE (cases) were compared to controls, and a subgroup of PLHIV was compared to HIV-negative participants. Demographics, socioeconomic variables, comorbidities, and clinical variables were compared between study groups. Patient data were obtained from institutional electronic medical records, and outcomes were measured at regularly scheduled appointments. Results We included 130 participants, of which 54 were PLHIV. The PLHIV subgroup was significantly younger (p = 0.01) and demonstrated significantly higher prevalences of chronic liver disease, previous viral hepatitis, daily alcohol consumption, and intravenous drug use (IDU). One-third of the participants had an AE (45 cases, 34.6%), with liver toxicity being the most common (22.3%). Participants who developed AEs were significantly older (p = 0.030) and had a higher prevalence of economic hardship (p = 0.037), as well as higher scores of the Charlson comorbidity index (p = 0.002) than the controls. INH withdrawal occurred in 17 participants (13.1%) and was mainly associated with liver toxicity (p < 0.01) and gastrointestinal symptoms (p = 0.022). In the adjusted effect model, an age ≥ 65 years, economic hardship, and excessive alcohol consumption were significantly associated with higher odds of AEs, while HIV infection decreased the odds by 68.4% (p = 0.033). Conclusions In our study, INH-associated AEs were common, with liver toxicity being the most frequent. Older age, economic hardship, and excessive alcohol consumption increased the odds of INH-associated AEs, while PLHIV had lower odds of developing INH-associated AEs, even when adjusting for other variables in the multivariate analysis. Further studies should be conducted to assess if these results are replicable in a larger population and in different settings.

PMID:37575717 | PMC:PMC10412740 | DOI:10.7759/cureus.41647

J Ethnopharmacol. 2023 Aug 10:117022. doi: 10.1016/j.jep.2023.117022. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Chemotherapy is a common cancer treatment strategy. However, its effectiveness is constrained by toxicity and adverse effects. The Lamiaceae herb Salvia miltiorrhiza Bunge has a long history of therapeutic use in the treatment of blood stasis illnesses, which are believed by traditional Chinese medicine to be connected to cancer.

AIM OF THE STUDY: This review summarized the common toxicity of chemotherapy and the potential chemo-adjuvant effect and mechanisms of active ingredients from S. miltiorrhiza, hoping to provide valuable information for the development and application of S. miltiorrhiza resources.

MATERIALS AND METHODS: The literatures were retrieved from PubMed, Web of Science, Baidu Scholar and Google Scholar databases from 2002 to 2022. The inclusion criteria were studies reporting that S. miltiorrhiza or its constituents enhanced the efficiency of chemotherapy drugs or reduced the side effects.

RESULTS: Salvianolic acid A, salvianolic acid B, salvianolic acid C, rosmarinic acid, tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone I and miltirone are the primary adjuvant chemotherapy components of S. miltiorrhiza. The mechanisms mainly involve inhibiting proliferation, metastasis, and angiogenesis, inducing apoptosis, regulating autophagy and tumor microenvironment. In addition, they also improve chemotherapy drug-induced side effects.

CONCLUSIONS: The bioactive compounds of S. miltiorrhiza are shown to inhibit proliferation, metastasis, and angiogenesis, induce apoptosis and autophagy, regulate immunity and tumor microenvironment when combined with chemotherapy drugs. However, further clinical studies are required to validate the current studies.

PMID:37572929 | DOI:10.1016/j.jep.2023.117022

BMC Anesthesiol. 2023 Aug 11;23(1):270. doi: 10.1186/s12871-023-02232-8.

ABSTRACT

BACKGROUND: This prospective, randomized, double-blind trial aimed to compare the postoperative analgesic efficacy of One-Level pre-incisional erector spinae plane block (ESPB) and Bi-Level pre-incisional ESPB in patients undergoing video-assisted thoracic surgery (VATS).

METHODS: This pilot trial was conducted between April 2022 and February 2023 with sixty patients. The patients were randomly divided into two groups. In One-Level ESPB Group (n = 30) block was performed at the thoracal(T)5 level with the 30 ml 0.25% bupivacaine. In the Bi-Level ESPB Group (n = 30) block was performed at T4 and T6 levels by using 15 ml of 0.25% bupivacaine for each level. In the postoperative period, 50 mg dexketoprofen every 12 h and 1 g paracetamol every 8 h were given intravenously (IV). Patient-controlled analgesia (PCA) prepared with morphine was applied to the patients. 0.5 mg/kg of tramadol was administered via IV for rescue analgesia. Visual analog scale (VAS) scores were recorded in the postoperative 1st, 2nd, 4th, 12th, 24th, and 48th -hours. The need for additional analgesics and side effects were recorded. In two groups, patients' demographics and postoperative hemodynamic data were recorded.

RESULTS: VAS scores at resting were statistically significantly higher at the 1st (p: 0.002) and 4th -hour (p: 0.001) in the One-Level ESPB. When the groups were evaluated in terms of VAS coughing scores, the 4th -hour (p: 0.001) VAS coughing scores results were found to be statistically significantly higher in the One-Level ESPB group. In terms of VAS values evaluated during follow-up, the rates of VAS coughing score > 3 values were found to be statistically significantly lower in the Bi-Level ESPB group (p: 0.011). There was no statistically significant difference between the groups in terms of side effects, morphine consumption, and additional analgesic use (p > 0.05).

CONCLUSIONS: Adequate analgesia was achieved in the early postoperative period in the group treated with Bi-Level ESPB with similar morphine consumption and side effects. This may be an advantage, especially in the early postoperative period when the pain is quite intense.

PMID:37568076 | PMC:PMC10416471 | DOI:10.1186/s12871-023-02232-8

Rev Alerg Mex. 2023 Jun 28;70(2):72-79. doi: 10.29262/ram.v70i2.1117.

ABSTRACT

OBJECTIVE: To determine prevalence, causes and risk factors of ADE in hospitalized patients of a General Hospital.

METHODS: Observational and analytical case-control study, carried out in patients hospitalized for adverse drug events, treated at the Hospital General Dr. Eduardo Vázquez N, in Puebla, Mexico, between, June 2019 to June 2021. For the statistical analysis, percentages, frequencies, means, odds ratio, χ2, and multiple binary logistic regression were used. Data were analyzed using the Statistical Package for the Social Sciences 23 program.

RESULTS: A total of 132 patients (66 cases and 66 controls) were registered. Of the group of cases, 26 patients treated for medication error and 40 with adverse drug reaction were reported. The prevalence of adverse drug events was 3.6%. The drugs and factors associated with the most reported adverse events were: antibiotics, anti-inflammatories; average age of 35 years (SD: 17.41); gender: 39.3% men, 60.7% women; services re-ported with the greatest attention: Emergencies and Surgery; frequent route of administration: intravenous (32.3%); main symptoms: skin; symptoms associated with adverse drug reactions: type A pruritus [OR: 8.5, p = 0.001(CI95%: 0.035-0.393)], type B pruritus [OR: 11, p = 0.001 (CI95%: 0.021-0.368)]; urticaria [OR: 19, p = 0.005(CI95%: 0.007-0.412)]. Risk factors associated with adverse events were: female gender [OR: 2.6, p = 0.05 (CI95%: 1.33-5.43)], history of allergy [OR: 3.4, p = 0.033 (CI95%: 1.04-8.40)] and prolonged hospital stay [OR: 5.4, p = 0.023 (CI95%: 3.82-6.74)].

CONCLUSIONS: The majority of ADEs were EM or ADR type A, both preventable reactions, so patient safety should be a priority when prescribing.

PMID:37566770 | DOI:10.29262/ram.v70i2.1117

Rev Alerg Mex. 2023 May 24;70(1):51-54. doi: 10.29262/ram.v70i1.1210.

ABSTRACT

BACKGROUND: The most common cause of hyperthyroidism is Graves' disease. Propylthiouracil (PTU) is one of the drugs used to treat this disease. Leukocytoclastic vasculitis is described among dermatologic adverse effects of PTU.

CASE REPORT: A 18-year-old woman, allergic to methimazole, developed a vasculitis associated to ANCAs with characteristics of leukocytoclastic vasculitis, associated to PTU treatment. She did not present systemic involvement. PTU treatment was suspended. Two months later, the skin lesions had almost completely resolved.

CONCLUSIONS: Leukocytoclastic vasculitis should be considered in the spectrum of complications caused by the consumption of propylthiouracil. The lesions can manifest over time, from a few weeks to years after taking the drug. When there is no systemic involvement, propylthiouracil suspension is sufficient to cure the disease.

PMID:37566757 | DOI:10.29262/ram.v70i1.1210

Annu Rev Pharmacol Toxicol. 2023 Aug 10. doi: 10.1146/annurev-pharmtox-033123-114106. Online ahead of print.

ABSTRACT

Each year over half a million people experience permanent hearing loss caused by treatment with therapeutic drugs with ototoxic side effects. There is a major unmet clinical need for therapies that protect against this hearing loss without reducing the therapeutic efficacy of these lifesaving drugs. At least 17 clinical trials evaluating 10 therapeutics are currently underway for therapies aimed at preventing aminoglycoside- and/or cisplatin-induced ototoxicity. This review describes the preclinical and clinical development of each of these approaches, provides updates on the status of ongoing trials, and highlights the importance of appropriate outcome measures in trial design and the value of reporting criteria in the dissemination of results. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:37562496 | DOI:10.1146/annurev-pharmtox-033123-114106

J Clin Pharmacol. 2023 Aug 10. doi: 10.1002/jcph.2334. Online ahead of print.

ABSTRACT

Imipenem/cilastatin/relebactam is approved for treatment of serious gram-negative bacterial infections in adults. This study assessed pharmacokinetics (PK), safety, and tolerability of a single dose of imipenem/cilastatin/relebactam (fixed 2:1 ratio of imipenem/cilastatin to relebactam, with a maximum dose of 15 mg/kg imipenem and 15 mg/kg cilastatin [≤500 mg imipenem and ≤500 mg cilastatin] and 7.5 mg/kg relebactam [≤250 mg relebactam]) in children with confirmed/suspected gram-negative bacterial infections receiving standard-of-care antibacterial therapy. In this phase 1, noncomparative study (ClinicalTrials.gov identifier, NCT03230916), the PK/pharmacodynamic (PD) target for imipenem was percent time of the dosing interval that unbound plasma concentration exceeded the minimum inhibitory concentration (%ƒT>MIC) of ≥30% (MIC = 2 μg/mL). For relebactam, the PK/PD target was free area under the concentration-time curve (AUC) normalized to MIC (at 2 μg/mL) ≥8.0 (equivalent to AUC from 0 extrapolated to infinity ≥20.52 μg∙h/mL), respectively. Safety was assessed up to 14 days after drug infusion. For imipenem, the ranges of geometric mean %fT>MIC and maximum concentration (Cmax ) across age cohorts were 56.5%-93.7% and 32.2-38.2 μg/mL, respectively. For relebactam, the ranges of geometric mean Cmax and AUC from 0 to 6 hours across age cohorts were 16.9-21.3 μg/mL and 26.1-55.3 μg·h/mL, respectively. 8/46 (17%) children experienced ≥1 adverse events and 2/46 (4%) children experienced nonserious adverse events that were deemed drug related by the investigator. Imipenem and relebactam exceeded plasma PK/PD targets; single doses of imipenem/cilastatin/relebactam were well tolerated with no significant safety concerns identified. These results informed imipenem/cilastatin/relebactam dose selection for further pediatric clinical evaluation. This article is protected by copyright. All rights reserved.

PMID:37562063 | DOI:10.1002/jcph.2334

J Addict Med. 2023 Aug 10. doi: 10.1097/ADM.0000000000001216. Online ahead of print.

ABSTRACT

OBJECTIVES: Xylazine is an α2-agonist increasingly prevalent in the illicit drug supply. Our objectives were to curate information about xylazine through social media from people who use drugs (PWUDs). Specifically, we sought to answer the following: (1) What are the demographics of Reddit subscribers reporting exposure to xylazine? (2) Is xylazine a desired additive? And (3) what adverse effects of xylazine are PWUDs experiencing?

METHODS: Natural language processing (NLP) was used to identify mentions of "xylazine" from posts by Reddit subscribers who also posted on drug-related subreddits. Posts were qualitatively evaluated for xylazine-related themes. A survey was developed to gather additional information about the Reddit subscribers. This survey was posted on subreddits that were identified by NLP to contain xylazine-related discussions from March 2022 to October 2022.

RESULTS: Seventy-six posts were extracted via NLP from 765,616 posts by 16,131 Reddit subscribers (January 2018 to August 2021). People on Reddit described xylazine as an unwanted adulterant in their opioid supply. Sixty-one participants completed the survey. Of those who disclosed their location, 25 of 50 participants (50%) reported locations in the Northeastern United States. The most common route of xylazine use was intranasal use (57%). Thirty-one of 59 (53%) reported experiencing xylazine withdrawal. Frequent adverse events reported were prolonged sedation (81%) and increased skin wounds (43%).

CONCLUSIONS: Among respondents on these Reddit forums, xylazine seems to be an unwanted adulterant. People who use drugs may be experiencing adverse effects such as prolonged sedation and xylazine withdrawal. This seemed to be more common in the Northeast.

PMID:37561586 | DOI:10.1097/ADM.0000000000001216

J Clin Psychiatry. 2023 Aug 7;84(4):sunscz3001sho. doi: 10.4088/JCP.sunscz3001sho.

ABSTRACT

Schizophrenia is a chronic and debilitating mental health condition that significantly impacts quality of life and can shorten patients' lifetime by decades. It is characterized by symptoms including hallucinations and delusions, apathy, and cognitive impairment, and people with schizophrenia also experience many somatic comorbidities, such as metabolic disturbances, infectious diseases, cardiovascular issues, and respiratory illnesses. For decades, treatment for schizophrenia has focused on antipsychotics (APs) that reduce excess dopamine signaling to the associative striatum, which also blocks dopamine signaling in the dorsal striatum, creating movement disorders. Second-generation APs have a lower propensity to cause drug-induced movement disorders than first-generation APs. Nonetheless, only 1 out of 3 patients respond to any of the available APs; moreover, negative and cognitive symptoms tend to persist, while side effects and long-term risks can contribute to poor outcomes. However, there are new understandings in how to reduce dopamine release both presynaptically and selectively in circuits governing psychotic symptoms. These mechanisms offer a different treatment approach for patients with schizophrenia.

PMID:37555680 | DOI:10.4088/JCP.sunscz3001sho

Ann Med Surg (Lond). 2023 Jul 10;85(8):4145-4149. doi: 10.1097/MS9.0000000000001067. eCollection 2023 Aug.

ABSTRACT

Secondary thrombocythemia (ST), also called reactive thrombocytosis, is caused by a disorder that triggers increased production by normal platelet-forming cells and is characterized by the abnormally increased number of platelet and megakaryocytes in the bone marrow. Previous reports have found complications from malignant tumors, chronic inflammation, acute inflammation, acute hemorrhage, splenectomy, etc. to be the common causes of ST. However, reports of secondary thrombocytosis caused by antibiotics are limited and there are no reports of secondary thrombocytosis with acute myocardial infarction as the first presentation. If the patient is at high risk of thrombosis, intensive antithrombotic therapy is required. To raise clinicians' awareness of drug-induced secondary thrombocytosis and to enhance antithrombotic therapy for high-risk patients, this article presented a case of drug-induced secondary thrombocytosis with acute ST-segment elevation myocardial infarction as the primary manifestation.

CASE PRESENTATION: An 80-year-old woman was admitted with cardiogenic shock due to post-activity chest pain. She was started on aspirin and clopidogrel antiplatelet therapy, then replaced aspirin with indolibuprofen, which has relatively few side effects. There was no significant decrease in platelet counts during treatment.

CLINICAL DISCUSSION: Secondary thrombocythemia, characterized by nonspecific symptoms, is difficult to diagnose. Secondary thrombocytosis with acute myocardial infarction as the first symptom is uncommon, but is very urgent and associated with a poor prognosis. What's more, cause-specific treatment counts for secondary thrombocythemia. Therefore it is important to search for the causal factor of secondary thrombocytosis. Secondary thrombocytosis caused by cephalosporins is rare. There is a need to arouse the attention of clinicians to the ST caused by cephalosporins and to provide a guide of treatment to these patients.

CONCLUSION: After a thorough analysis of the pertinent literature, we discovered that several retrospective studies demonstrated the effectiveness of cytoreductive therapy in significantly reducing platelet counts. Based on this finding, we prescribed hydroxyurea to our patient, which led to a gradual decrease in platelet count and ultimately resulted in a return to normal levels.

PMID:37554887 | PMC:PMC10405984 | DOI:10.1097/MS9.0000000000001067

Expert Opin Drug Saf. 2023 Aug 9. doi: 10.1080/14740338.2023.2245745. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study is to monitor, identify, and compare the adverse events (AEs) related to tenecteplase and alteplase, with the objective of exploring the potential safety of tenecteplase for acute ischemic stroke (AIS) and guiding its use to enhance patient safety.

METHODS: In order to evaluate the disproportionality of AEs associated with tenecteplase and alteplase in real-world data, four algorithms (ROR, PRR, BCPNN, EBGM) were utilized as measures to detect signals of AEs related to both drugs. Subsequently, Breslow-Day statistical analysis was applied to compare the RORs of the main system organ classes (SOCs) and key preferred terms (PTs) between tenecteplase and alteplase.

RESULTS: A statistical analysis was performed utilizing data gleaned from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, encompassing 19,514,140 case reports from 2004Q1 to 2023Q1. There were 1,004 cases where tenecteplase was reported as the primary suspected (PS) and 2,363 tenecteplase-related adverse drug reactions (ADRs) at the PTs level were identified, the two data of alteplase were 10,945 and 25,266, respectively. The occurrence of drug-induced ADRs was analyzed across 27 organ systems, The analysis revealed several expected ADRs, such as Haemorrhage, Hypersensitivity which were consistent with the two drug-labels. It is of note that the signal strengths of 'death,' 'ventricular fibrillation,' 'cardiogenic shock' and 'pneumonia aspiration' at the PT level were markedly higher for tenecteplase than for alteplase, whereas the signal strength of 'angioedema' at the PT level was significantly higher for alteplase in comparison to tenecteplase. Additionally, unexpected significant ADRs associated with ocular adverse reactions and pneumonia aspiration at the PT level were identified, indicating potential AEs not currently mentioned in the drug instructions.

CONCLUSION: This study identified and compared signals of ADRs associated with tenecteplase and alteplase, although tenecteplase is as effective as alteplase and has advantages such as ease of use and affordability, it cannot replace alteplase in the treatment of AIS until its safety profile is fully recognized. Additionally, previously unreported ocular ADRs and pneumonia were identified, providing valuable insights into the relationship between ADRs and the use of these thrombolytic drugs. These findings underscore the importance of continuous monitoring and effective detection of AEs to ultimately enhance the safety of AIS patients undergoing thrombolytic therapy.

PMID:37554093 | DOI:10.1080/14740338.2023.2245745

BMC Geriatr. 2023 Aug 8;23(1):477. doi: 10.1186/s12877-023-04131-6.

ABSTRACT

BACKGROUND: On average, older patients use five or more medications daily. A consequence is an increased risk of adverse drug reactions, interactions, or medication errors. Therefore, it is important to understand the challenges experienced by the patients, relatives, and healthcare professionals pertinent to the concomitant use of many drugs.

METHODS: We conducted a qualitative study using focus group interviews to collect information from patients, relatives, and healthcare professionals regarding older patients' management of prescribed medicine. We interviewed seven patients using five or more medications daily, three relatives, three general practitioners, nine nurses from different healthcare sectors, one home care assistant, two hospital physicians, and four pharmacists.

RESULTS: The following themes were identified: (1) Unintentional non-adherence, (2) Intentional non-adherence, (3) Generic substitution, (4) Medication lists, (5) Timing and medication schedule, (6) Medication reviews and (7) Dose dispensing/pill organizers.

CONCLUSION: Medication is the subject of concern among patients and relatives. They become confused and insecure about information from different actors and the package leaflets. Therefore, patients often request a thorough medication review to provide an overview, knowledge of possible side effects and interactions, and a clarification of the medication's timing. In addition, patients, relatives and nurses all request an indication of when medicine should be taken, including allowable deviations from this timing. Therefore, prescribing physicians should prioritize communicating information regarding these matters when prescribing.

PMID:37553585 | PMC:PMC10410867 | DOI:10.1186/s12877-023-04131-6

Nature. 2023 Aug;620(7973):277. doi: 10.1038/d41586-023-02495-8.

NO ABSTRACT

PMID:37553462 | DOI:10.1038/d41586-023-02495-8

BMJ Open. 2023 Aug 8;13(8):e073304. doi: 10.1136/bmjopen-2023-073304.

ABSTRACT

OBJECTIVE: Although adverse drug reactions (ADRs) are quite common in hospitalised neonates, pharmacovigilance activities in this public are still incipient. This study aims to characterise ADRs in neonates in a neonatal intensive care unit (NICU), identifying causative drugs, temporal profile and associated factors.

DESIGN: Prospective observational study.

SETTING: NICU of a public maternity hospital in Natal/Brazil.

PARTICIPANTS: All neonates admitted to the NICU for more than 24 hours and using at least one medication were followed up during the time of hospitalisation.

PRIMARY OUTCOME MEASURES: Incidence rate and risk factors for ADRs. The ADRs were detected by an active search in electronic medical records and analysis of spontaneous reports in the hospital pharmacovigilance system.

RESULTS: Six hundred neonates were included in the study, where 118 neonates had a total of 186 ADRs. The prevalence of ADRs at the NICU was 19.7% (95% CI 16.7% to 23.0%). The most common ADRs were tachycardia (30.6%), polyuria (9.1%) and hypokalaemia (8.6%). Tachycardia (peak incidence rate: 57.1 ADR/1000 neonates) and hyperthermia (19.1 ADR/1000 neonates) predominated during the first 5 days of hospitalisation. The incidence rate of polyuria and hypokalaemia increased markedly after the 20th day, with both reaching a peak of 120.0 ADR/1000 neonates. Longer hospitalisation time (OR 0.018, 95% CI 0.007 to 0.029; p<0.01) and number of prescribed drugs (OR 0.127, 95% CI 0.075 to 0.178; p<0.01) were factors associated with ADRs.

CONCLUSION: ADRs are very common in NICU, with tachycardia and hyperthermia predominant in the first week of hospitalisation and polyuria and hypokalaemia from the third week onwards.

PMID:37553191 | DOI:10.1136/bmjopen-2023-073304

JAMA Netw Open. 2023 Aug 1;6(8):e2327739. doi: 10.1001/jamanetworkopen.2023.27739.

ABSTRACT

IMPORTANCE: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management.

OBJECTIVE: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada.

EVIDENCE REVIEW: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023.

FINDINGS: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed.

CONCLUSIONS AND RELEVANCE: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

PMID:37552484 | DOI:10.1001/jamanetworkopen.2023.27739

Eur J Hosp Pharm. 2023 Aug 8:ejhpharm-2023-003849. doi: 10.1136/ejhpharm-2023-003849. Online ahead of print.

ABSTRACT

A man with diffuse large B-cell lymphoma in the nasal cavity was treated with sindilizumab, an immune checkpoint inhibitor, combined with local radiotherapy for multiple nodules of the left upper arm. After a single administration of sindilizumab and 10 radiotherapy treatments, the patient presented with liver dysfunction. Liver function tests showed that the levels of transaminases had increased abnormally and deteriorated though with intense treatment. His bilirubin level was also increased with obvious yellow staining of the skin and sclera. The patient was considered to have severe immune-mediated hepatitis (IMH) caused by sindilizumab combined with local radiotherapy. His liver function did not improve and he died of organ failure. This is a case of rare liver failure which was considered to be IMH induced by synergistic treatment with immune checkpoint therapy and radiotherapy.

PMID:37553230 | DOI:10.1136/ejhpharm-2023-003849

BMC Pulm Med. 2023 Aug 8;23(1):289. doi: 10.1186/s12890-023-02569-3.

ABSTRACT

BACKGROUND: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has demonstrated effectiveness in treating ovarian, breast, and other cancers, particularly those with specific molecular subtypes including, but not limited to, BRCA1/2 mutations. Consequently, its utilization is expected to increase in the future. For this reason, it is important to acknowledge the potential for adverse events associated with olaparib, including the relatively rare but significant risk of drug-induced interstitial lung disease (DIILD). Since DIILD can lead to fatal outcomes, its early detection is crucial. The dissemination of knowledge regarding DIILD can be facilitated through case reports; however, specific reports of DIILD caused by olaparib have only been published in Japanese. To the best of our knowledge, this is the first report in English of our experience with three cases of DIILD caused by olaparib.

CASE PRESENTATION: Cases 1, 2, and 3 involved Japanese women with ovarian cancer who had been receiving olaparib at a dose of 600 mg/day. Case 1, a 72-year-old woman who had been on olaparib for 4 months, and case 2, a 51-year-old woman who had been on olaparib for 8 months, reported fever and general malaise. Chest computed tomography (CT) revealed pale ground glass opacity (GGO) similar to hypersensitivity pneumonitis. The severity grade was 2 in both cases. Case 3, a 78-year-old woman who had been on olaparib for 3 weeks, presented with cough and reported dyspnea on exertion. Chest CT revealed non-specific interstitial pneumonia and organizing pneumonia-like shadows. The severity grade was 4. Olaparib was discontinued in all cases. Case 1 received 0.6 mg/kg of prednisolone due to mild hypoxia, while prednisolone was not administered in case 2 due to the absence of hypoxia. Case 3 received steroid pulse therapy due to severe hypoxia. Olaparib administration was not resumed in any patient.

CONCLUSION: DIILD caused by olaparib in Japan, including the present three cases, commonly presents with GGO, similar to hypersensitivity pneumonitis on chest CT. The prognosis for the majority of patients is favorable; however, there have been instances of severe cases. Early recognition of drug-induced lung injury and further accumulation of cases is important.

PMID:37553592 | DOI:10.1186/s12890-023-02569-3

Int J Crit Illn Inj Sci. 2023 Apr-Jun;13(2):78-81. doi: 10.4103/ijciis.ijciis_85_22. Epub 2023 Jun 26.

ABSTRACT

Asciminib, a "Specifically Targeting the ABL Myristoyl Pocket" inhibitor, is a new drug in the treatment of tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML). Hemocytopenias associated with asciminib are common adverse events documented by clinical trials. We report a case of precipitous-onset pancytopenia with the initiation of asciminib treatment in a patient with TKI-resistant CML. This case had a confounding array of laboratory findings that evidenced a drug-induced hemophagocytic component. We hope that our case stimulates further reporting of similar cases to enhance the understanding of the pathophysiology underlying asciminib-induced hemocytopenias.

PMID:37547190 | PMC:PMC10401557 | DOI:10.4103/ijciis.ijciis_85_22