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

Drug Ther Bull. 2022 Dec 13:dtb-2022-000071. doi: 10.1136/dtb.2022.000071. Online ahead of print.

NO ABSTRACT

PMID:36600442 | DOI:10.1136/dtb.2022.000071

J Exp Clin Cancer Res. 2023 Jan 5;42(1):4. doi: 10.1186/s13046-022-02568-y.

ABSTRACT

BACKGROUND: Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients.

METHODS: irAEs associated with seven FDA-approved ICIs, including three PD-1 inhibitors (cemiplimab, nivolumab and pembrolizumab), three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab), and one CTLA-4 inhibitor (ipilimumab), were analyzed based on data from 149,303 reported cases (from January 1, 2015 to June 30, 2022) collected from the FDA Adverse Events Reporting System (FAERS) public dashboard. Proportions of serious irAEs and correlations with tumor type, age and sex were assessed via R package and GraphPad software.

RESULTS: irAEs related to anti-PD-1 ICIs required less hospital care resources compared with anti-PD-L1 and anti-CTLA-4 ICIs. Patients treated with pembrolizumab had relatively fewer serious cases. Treatment with ICIs led to the highest probability of serious irAEs in patients with lung cancer. 'Respiratory, thoracic and mediastinal disorders' and 'gastrointestinal disorders' were the two most common groups of disorders caused by the seven ICIs studied. 'Cardiac disorders' was the main type of disorders caused by these ICIs in cancer patients aged 65-85, while 'reproductive system and breast disease' was the main type of disorder in cancer patients aged 18-64. 'Respiratory, thoracic, mediastinal diseases' and 'reproductive system and breast diseases' were the main types of disorders associated with treatment with these ICIs in male and female patients, respectively.

CONCLUSION: Tissue and organ toxicities of ICIs are age and sex specific. There are risks of respiratory and urinary system toxicity in male patients and reproductive system toxicity in female patients treated with the ICIs studied. Future studies on the toxicity burden of ICIs should incorporate age and sex differences to better understand the relevance of ICI toxicity burden to human immune function to develop appropriate tumor immune and therapeutic intervention strategies.

PMID:36600271 | DOI:10.1186/s13046-022-02568-y

BMJ Case Rep. 2023 Jan 4;16(1):e251974. doi: 10.1136/bcr-2022-251974.

ABSTRACT

Risperidone and aripiprazole are increasingly used for behavioural indications in children and adolescents with intellectual disabilities, including autism. Although there are some reports in literature, the side effect profile in this population remains poorly defined and there is a need to raise awareness among clinicians across specialties. We present two patients with significant intellectual disabilities who developed extrapyramidal side effects (EPSE) including oculogyric crisis following risperidone and aripiprazole use. The onset of these side effects can be insidious and the non-specific nature of the presentation, for example, poor mobility and increased drooling on a background of severe intellectual disability, can lend itself to delay in recognition and reporting by families. There is also reduced awareness among paediatricians, which can further delay the treatment of this reversible condition. There needs to be ongoing vigilance for EPSE as they can develop years after treatment has been initiated.

PMID:36599495 | DOI:10.1136/bcr-2022-251974

J Toxicol Sci. 2023;48(1):1-14. doi: 10.2131/jts.48.1.

ABSTRACT

Although microsampling of blood is recommended to promote the 3Rs in toxicokinetic (TK) evaluation, there are few reports applying microsampling in actual toxicity evaluation. Here, we assessed the effects of microsampling on toxicological evaluation of methapyrilene hydrochloride, a hepatotoxic substance. Female SD rats received methapyrilene hydrochloride orally at dose levels of 0 (vehicle), 10, and 30 mg/kg BW, once daily for 4 weeks. Each dose level included a microsampling group and a non-microsampling group (n = 5). In the microsampling groups, blood sampling (50 µL/time point) was performed at 6 time points on day 1 of administration and 7 time points on day 27-28; all the animals underwent necropsy on day 29. Toxicity studies and TK analysis were performed, and through these studies in 2 organizations, cross-organization validation of the effect on toxicity evaluation was conducted. In one organization, microsampling obscured changes in some parameters in hematology due to the administration of methapyrilene hydrochloride. In the other organization, although the relationship between the developing pattern of histopathological findings in the liver and the blood sampling was suspected, it was associated with poor reproducibility; this was considered as a change within a variation range of biological reactions. Each of these phenomena was observed in only one organization without consistency. In both organizations, no effect of blood microsampling was observed in other endpoints. In conclusion, microsampling is considered to be a technique applicable to safety studies of drugs showing hepatotoxicity, as it did not show a marked influence on the toxicological evaluation of methapyrilene hydrochloride.

PMID:36599423 | DOI:10.2131/jts.48.1

Praxis (Bern 1994). 2023 Jan;112(1):5-10. doi: 10.1024/1661-8157/a003960.

ABSTRACT

Choosing Wisely in Patients with Polypharmacy Abstract. Polypharmacy and potentially inappropriate medication have a negative impact on health. For reducing or stopping medication (deprescribing) patient benefits are crucial. The following stepwise approach has turned out to be successful: a. ask patients to bring along all their medication and compare them with the current medication list; b. offer shared decision making; c. evaluate every drug for indication, balance between benefit and harm, side effects and dose; d. prioritize benefit and harm according to values, preferences and goals of the patient; e. decide together about deprescribing; f. track changes in the medication plan und arrange a follow-up consultation. We illustrate this approach by the example of an older, frail female patient with polypharmacy. Deprescribing is just as important for patients' well-being as is prescribing!

PMID:36597681 | DOI:10.1024/1661-8157/a003960

J Coll Physicians Surg Pak. 2023 Jan;33(1):107-108. doi: 10.29271/jcpsp.2023.01.107.

ABSTRACT

Medication errors cause harm to patients at any point along the medication administration process and can be prevented. Barcoding medication administration (BCMA) is effective as a clinical decision support system (CDSS) to avoid errors. This viewpoint proposes the implementation of BCMA to avoid potential adverse events. The opinion piece gives an overview of BCMA, reviews the current literature on its effectiveness, and sheds light on the associated challenges and how to overcome them. The objective of this article is to increase awareness regarding BCMA and how it can decrease patient morbidity and mortality, enhance safety, and lower overall hospital-associated costs by preventing medication errors. Key Words: Bar-code medication administration, Medication errors, Adverse drug events, Patient safety.

PMID:36597245 | DOI:10.29271/jcpsp.2023.01.107

BMC Med. 2023 Jan 4;21(1):2. doi: 10.1186/s12916-022-02669-7.

ABSTRACT

BACKGROUND: HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.

METHODS: This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D.

RESULTS: Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months.

CONCLUSIONS: The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations.

TRIAL REGISTRATION: Trial registration ClinicalTrials.gov number: NCT03973151.

PMID:36600247 | DOI:10.1186/s12916-022-02669-7

Drug Ther Bull. 2023 Jan 4:dtb-2022-000077. doi: 10.1136/dtb.2022.000077. Online ahead of print.

ABSTRACT

Overview of: Joy M, Williams J, Emanuel S, et al Trends in direct oral anticoagulant (DOAC) prescribing in English primary care (2014-2019). Heart 2022. doi: 10.1136/heartjnl-2022-321377. [Epub ahead of print 9 Sept 2022].

PMID:36599656 | DOI:10.1136/dtb.2022.000077

J Clin Anesth. 2023 Jan 2;85:111047. doi: 10.1016/j.jclinane.2022.111047. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: Ciprofol, a novel intravenous anesthetic, provides rapid recovery in patients undergoing colonoscopy. We aimed to examine the efficacy and safety of ciprofol in comparison with propofol for sedation or anesthesia in non-operating room settings including endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and flexible bronchoscopy (FB).

DESIGN: Prospective, randomized, double-blind, parallel-group clinical trial.

SETTING: University-affiliated teaching hospital.

PATIENTS: We recruited 207 patients scheduled for an endoscopic procedure from October 2021 to December 2021.

INTERVENTIONS: Patients were randomized into three groups according to the dose during induction (n = 69 each): 1) ciprofol 6 mg/kg/h, 2) ciprofol 8 mg/kg/h, or 3) propofol 40 mg/kg/h. Ciprofol or propofol was administered throughout the procedure.

MEASUREMENTS: The primary outcome was the success rate of sedation or anesthesia for the procedures. Secondary outcomes included induction time, endoscope insertion time, recovery time, discharge time, incidence of drug-related adverse events (AEs), neurological and inflammatory outcomes.

MAIN RESULTS: The procedure success rates in the three groups were 100%. The induction time in the 6 (3.3 ± 1.0 min) and 8 mg/kg/h (2.9 ± 0.6 min) ciprofol groups was longer than that in the propofol group (2.5 ± 0.6 min) only in patients undergoing FB (p = 0.004). The time for patients to be fully alert and discharged from the post-anesthesia care unit was comparable across the three groups (p > 0.05). The incidence of drug-related AEs in the propofol and 6 and 8 mg/kg/h ciprofol groups was 84.1%, 76.8%, and 79.7%. No pain on injection was reported by ciprofol groups. Neurological outcomes and inflammatory responses were comparable among the three groups.

CONCLUSIONS: Ciprofol induced a level of sedation or anesthesia equivalent to that induced by propofol in non-operating room settings except for a prolonged induction time in patients undergoing FB. Ciprofol had a safety profile similar to that of propofol. No pain on injection was reported by ciprofol.

PMID:36599219 | DOI:10.1016/j.jclinane.2022.111047

JCO Oncol Pract. 2023 Jan 4:OP2200447. doi: 10.1200/OP.22.00447. Online ahead of print.

ABSTRACT

PURPOSE: Several new treatment combinations have been approved in metastatic renal cell carcinoma (mRCC). To determine the optimal therapy on the basis of cost and health outcomes, we performed a cost-effectiveness analysis of approved immunotherapy-tyrosine kinase inhibitor/immunotherapy drug combinations and sunitinib using public payer acquisition costs in the United States.

METHODS: We constructed a decision model with a 10-year time horizon. The seven treatment drug strategies included atezolizumab + bevacizumab, avelumab + axitinib, pembrolizumab + axitinib, nivolumab + ipilimumab (NI), nivolumab + cabozantinib, lenvatinib + pembrolizumab, and sunitinib. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values on the basis of the published literature. Costs included drug acquisition costs and costs for management of grade 3-4 drug-related adverse events. We used a partitioned survival model in which patients with mRCC transitioned between three health states (progression-free, progressive disease, and death) at monthly intervals on the basis of parametric survival function estimated from published survival curves. To determine cost-effectiveness, we constructed incremental cost-effectiveness ratios (ICERs) by dividing the difference in cost by the difference in effectiveness between nondominated treatments.

RESULTS: The least expensive treatment was sunitinib ($357,948 US dollars [USD]-$656,100 USD), whereas the most expensive was either lenvatinib + pembrolizumab or pembrolizumab + axitinib ($959,302 USD-$1,403,671 USD). NI yielded the most QALYs (3.6), whereas avelumab + axitinib yielded the least (2.5). NI had an incremental ICER of $297,465 USD-$348,516 USD compared with sunitinib. In sensitivity analyses, this ICER fell below $150,000 USD/QALY if the initial 4-month cost of NI decreased by 22%-38%.

CONCLUSION: NI was the most effective combination for mRCC, but at a willingness-to-pay threshold of $150,000 USD/QALY, sunitinib was the most cost-effective approach.

PMID:36599117 | DOI:10.1200/OP.22.00447