J Psychopharmacol. 2024 Aug;38(8):690-700. doi: 10.1177/02698811241265756. Epub 2024 Jul 31.

ABSTRACT

OBJECTIVE: Despite considerable research examining the efficacy of psychedelic-assisted therapies (PATs) for treating psychiatric disorders, assessment of adverse events (AEs) in PAT research has lagged. Current AE reporting standards in PAT trials are poorly calibrated to features of PAT that distinguish it from other treatments, leaving many potential AEs unassessed.

METHODS: A multidisciplinary working group of experts involved in PAT pooled formally and informally documented AEs observed through research experience and published literature. This information was integrated with (a) current standards and practices for AE reporting in pharmacotherapy and psychotherapy trials and (b) published findings documenting post-acute dosing impacts of psychedelics on subjective states, meaning, and psychosocial health variables, to produce a set of AE constructs important to evaluate in PAT as well as recommended methods and time frames for their assessment and monitoring. Correspondence between identified potential AEs and current standards for AE assessment was examined, including the extent of coverage of identified AE constructs by 25 existing measures used in relevant research.

RESULTS: Fifty-four potential AE terms warranting systematized assessment in PAT were identified, defined, and categorized. Existing measures demonstrated substantial gaps in their coverage of identified AE constructs. Recommendations were developed for how to assess PAT AEs (including patient, clinician, and informant reports), and when to assess over preparation, dosing session, integration, and follow-up. Application of this framework is demonstrated in a preliminary assessment protocol (available in the supplement).

CONCLUSIONS: This assessment framework addresses the need to capture post-acute dosing AEs in PAT, accounting for its pharmacotherapy and psychotherapy components, as well as documented impacts of psychedelics on worldviews and spirituality.

PMID:39082259 | DOI:10.1177/02698811241265756

Cardiovasc Toxicol. 2024 Jul 31. doi: 10.1007/s12012-024-09906-w. Online ahead of print.

ABSTRACT

Cardiac toxicity is an adverse event of several classes of anti-cancer drugs. Herein, we present the case of a 52-year-old woman with metastatic renal cell carcinoma (RCC), previously treated with debulking surgery, pembrolizumab (immune checkpoint inhibitor) in combination with axitinib (tyrosine kinase inhibitor (TKI)), followed by lenvatinib (TKI) and belzutifan (HIF-2α inhibitor), who developed myocarditis proven by cardiac magnetic resonance and endomyocardial biopsy. The case was notable for reporting a not-yet described adverse event during treatment with belzutifan plus lenvatinib, the etiology of which was of unobvious determination given the pre-exposure to pembrolizumab, a known cause of drug-related myocarditis. We surmise that myocarditis was a delayed adverse event related to pembrolizumab (8 months after treatment interruption), although we emphasize that only attentive monitoring of cardiac adverse events of patients exposed to belzutifan and lenvatinib in the context of large clinical trials may rule out any causal implication of these drugs.

PMID:39085529 | DOI:10.1007/s12012-024-09906-w

Zhonghua Yan Ke Za Zhi. 2024 Aug 11;60(8):704-712. doi: 10.3760/cma.j.cn112142-20231227-00312.

ABSTRACT

With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.

PMID:39085162 | DOI:10.3760/cma.j.cn112142-20231227-00312

J Microbiol Immunol Infect. 2024 Jul 14:S1684-1182(24)00114-2. doi: 10.1016/j.jmii.2024.07.003. Online ahead of print.

ABSTRACT

BACKGROUND: The ongoing, observational BICSTaR (BICtegravir Single Tablet Regimen) cohort study is evaluating real-world effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV across 14 countries over 24 months. We present 12-month data from the BICSTaR Asia cohort.

METHODS: Data were pooled from retrospective and prospective cohorts of antiretroviral therapy (ART)-naïve (hereafter, TN) and ART-experienced (hereafter, TE) people with HIV (aged ≥21 years) receiving B/F/TAF in routine clinical care in the Republic of Korea, Singapore, and Taiwan. Analyses included effectiveness (primary endpoint: HIV-1 RNA <50 copies/ml, missing = excluded analysis), CD4 count, CD4/CD8 ratio, safety, treatment persistence, and patient-reported outcomes (prospective group).

RESULTS: The analysis population included 328 participants (80 retrospective, 248 prospective; 65 TN, 263 TE). Participants were predominantly male (96.9% TN, 93.2% TE) with ≥1 comorbidity (52.3% TN, 57.8% TE); median age (years) was 31 (TN) and 42 (TE). Following 12 months of B/F/TAF, HIV-1 RNA was <50 copies/ml in 98.2% (54/55) of TN and 97.0% (227/234) of TE participants. Median (Q1, Q3) CD4 cell count increased by +187 (119, 291) cells/μl in the TN group (p < 0.001) and remained stable (+8 [-91, 110] cells/μl) in the TE group. B/F/TAF persistence was high in the prospective group, with 1/34 (2.9%) TN and 5/214 (2.3%) TE participants discontinuing treatment within 12 months. Drug-related adverse events occurred in 5.8% (19/328) of participants, leading to treatment discontinuation in 0.6% (2/328).

CONCLUSIONS: Real-world evidence from BICSTaR supports the effectiveness, safety and tolerability of B/F/TAF in people with HIV in Asia.

PMID:39079772 | DOI:10.1016/j.jmii.2024.07.003

Cureus. 2024 Jun 28;16(6):e63353. doi: 10.7759/cureus.63353. eCollection 2024 Jun.

ABSTRACT

Stevens-Johnson Syndrome (SJS) constitutes a rather uncommon, and rarely fatal hypersensitivity reaction that primarily impacts the skin and mucous membranes and in certain cases may be attributed to drug administration. The aim of this article is to present a case of etoricoxib-induced SJS in a 46-year-old, female patient. The patient presented herself, as a medical emergency, to the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, reporting pain, especially acute pain while eating certain foods, discomfort, dysphagia, and a wound in the left half of the hard palate. The clinical examination revealed a broad ulcer, in the left half of the hard palate as well as multiple ulcerations and erosions in the upper and lower lip. Her medical history was clear; however, the patient mentioned to have received etoricoxib, due to severe back pain, one day prior to our clinical examination. The patient received methylprednisolone 16 mg, twice per day, for two days, followed by methylprednisolone 8 mg, twice per day, for two more days. Her symptoms resigned and since the connection between etoricoxib and SJS was established, the patient was advised to avoid etoricoxib and be wary of adverse effects, when taking drugs especially non-steroidal anti-inflammatory medication. This is one of the first case reports in the literature, linking etoricoxib administration with the emergence of SJS, highlighting the importance of pharmacovigilance. The up-to-date registration of drug-induced adverse effects is of immense importance to protect future patients. SJS does not have a defined treatment strategy. Therefore, most patients are given supportive care and symptomatic treatment, which most commonly involves corticosteroids and antivirals such as acyclovir.

PMID:39077250 | PMC:PMC11283930 | DOI:10.7759/cureus.63353

Rev Cardiovasc Med. 2024 Feb 27;25(3):74. doi: 10.31083/j.rcm2503074. eCollection 2024 Mar.

ABSTRACT

The development of anti-tumor drugs has notably enhanced the survival rates and quality of life for patients with malignant tumors. However, the side effects of these drugs, especially cardiotoxicity, significantly limit their clinical application. The cardiotoxicity associated with anti-tumor drugs has been a subject of extensive attention and research. Traditional to mitigate these side effects have included reducing drug dosages, shortening treatment duration, modifying administration methods, and opting for drugs with lower toxicity. However, either approach may potentially compromise the anti-tumor efficacy of the medications. Therefore, exploring other effective methods for anti-cardiotoxicity will be the focus of future research. The potential of traditional Chinese medicine (TCM) in managing cardiovascular diseases and cancer treatment has gained widespread recognition. TCM is valued for its minimal side effects, affordability, and accessibility, offering promising avenues in the prevention and treatment of cardiotoxicity caused by anti-tumor drugs. Among its constituents, flavonoids, which are present in many TCMs, are particularly notable. These monomeric compounds with distinct structural components have been shown to possess both cardiovascular protective properties and anti-tumor capabilities. In this discussion, we will delve into the classification of anti-tumor drugs and explore the underlying mechanisms of their associated cardiotoxicity. Additionally, we will examine flavonoids found in TCM and investigate their mechanisms of cardiovascular protection. This will include an analysis of how these natural compounds can mitigate the cardiac side effects of anti-tumor therapies while potentially enhancing overall patient health and treatment outcomes.

PMID:39076949 | PMC:PMC11263839 | DOI:10.31083/j.rcm2503074

Rev Cardiovasc Med. 2022 Nov 9;23(11):380. doi: 10.31083/j.rcm2311380. eCollection 2022 Nov.

ABSTRACT

Lipid-lowering therapy is of great importance in reducing the burden of atherosclerotic cardiovascular disease. Statins act as first-line therapy in the current lipid management guidelines. However, statin use is limited in (1) statin-induced adverse events, including statin-associated muscle symptoms, new-onset diabetes mellitus, drug-induced liver injuries, acute kidney injuries, cognitive effects, hemorrhagic strokes, and cataracts; (2) special populations, including pregnant and lactating patients, patients with decompensated cirrhosis, and patients on dialysis; (3) coadministration with statin-interactive drugs, such as anti-human immunodeficiency virus drugs, anti-hepatitis C virus drugs, and immunosuppressive drugs. These considerable statin-limited groups are in urgent need of safer alternative lipid-lowering options. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are attracting widespread attention for their documented safety in general populations and superior lipid-lowering properties. Therefore, questions have been raised whether PCSK9 inhibitors could be a safe alternative in patients who are intolerant to statin therapy. In this review, we discuss the safety of PCSK9 inhibitors in statin-limited conditions. We conclude that PCSK9 inhibitors are a safe alternative lipid-lowering therapy in various statin-limited conditions. Furthermore, we identify several limitations in the current literature and suggest future directions, for the refinement of lipid management regimens.

PMID:39076187 | PMC:PMC11269069 | DOI:10.31083/j.rcm2311380

Reg Anesth Pain Med. 2024 Jul 29:rapm-2024-105835. doi: 10.1136/rapm-2024-105835. Online ahead of print.

NO ABSTRACT

PMID:39074953 | DOI:10.1136/rapm-2024-105835

Clin Transl Gastroenterol. 2024 Jul 29. doi: 10.14309/ctg.0000000000000754. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Peptic ulcer disease (PUD) and post-procedural artificial ulcers are common ulcer disease. For them, Proton pump inhibitor (PPI) and potassium-competitive acid blocker (P-CAB) are commonly used in clinical practice. PPI requires acid, time, and multiple doses, but P-CAB has fewer limitations. We compared the efficacy, safety and prevention of PPI and P-CAB in PUD and artificial ulcer.

METHODS: We searched PubMed, ClinicalTrials.gov, Embase, Cochrane Library, and Web of Science databases for all studies. All eligible randomized controlled trials up to August 5, 2023 were included. Healing rates, shrinking rates, treatment-emergent adverse events rates and recurrence rates were measured. Risk of bias, sensitivity analyses, and heterogeneity were also performed.

RESULT: 20 researches which were selected from 926 screening studies and in total 6567 participants were included. The risk ratio (RR) of healing rate with P-CABs versus PPIs of PUD at 4-week was RR 1.01 (95% CI 0.98-1.04). In addition, the healing rate distinction of artificial peptic ulcer was RR 1.04 (0.89-1.22), and the shrinking rate was MD 0.10 (-1.30-1.51). The result of TEAEs rate of PUD was RR 1.11 (0.91-1.35) and the delayed bleeding rate of artificial ulcer was RR 0.35 (0.16-0.80). The RR for recurrence rate of drug-related ulcers was 0.45 (0.25-0.81).

CONCLUSION: P-CAB is non-inferior in healing artificial ulcer and conventional PUD, also the incidence of TEAEs. But there may be a statistical advantage in holding back delayed bleeding and preventing drug-induced ulcers. More standardized experiments are needed for further applications and more precise conclusions.

PMID:39072507 | DOI:10.14309/ctg.0000000000000754

J Pain Res. 2024 Jul 22;17:2431-2441. doi: 10.2147/JPR.S453806. eCollection 2024.

ABSTRACT

PURPOSE: This study compared the efficacy, tolerability, and safety of rimegepant 75 mg oral tablet - a small molecule calcitonin-gene receptor peptide (CGRP) receptor antagonist - with placebo in the acute treatment of migraine.

METHODS: This double-blind, randomized, placebo-controlled trial enrolled adults aged ≥18 years with at least a 1-year history of migraine. Participants randomized to rimegepant 75 mg oral tablet or placebo treated a single migraine attack of moderate or severe pain intensity. The coprimary endpoints, pain freedom and freedom from the most bothersome symptom ([MBS] nausea, photophobia, or phonophobia) at 2 hours postdose, were evaluated using Mantel-Haenszel risk estimation.

RESULTS: Of the 1485 participants enrolled, 1162 (78.2%) were randomized to rimegepant (n = 582) or placebo (n = 580). Most participants (85.5%) were female; the population had a mean (SD) age of 41.6 (12.2) years and a history of 4.7 (1.8) migraine attacks per month. At 2 hours postdose, rimegepant-treated participants had higher pain freedom rates (19.2% [104/543] vs 14.2% [77/541]; risk difference 4.9; 95% confidence interval [CI] 0.5 to 9.3; P=0.0298) and MBS freedom rates (36.6% [199/543] vs 27.7% [150/541]; risk difference 8.9; 95% CI 3.4 to 14.4; P=0.0016) than placebo-treated participants. Rimegepant-treated participants also had higher rates of pain relief (56.0% [304/543] vs 45.7% [247/541]; risk difference 10.3; 95% CI 4.4 to 16.2, P=0.0006) at 2 hours postdose. The most common adverse events were nausea (0.9% [5/546] vs 1.1% [6/549]) and dizziness (0.7% [4/546] vs 0.4% [2/549]). No signal of drug-induced liver injury due to rimegepant was identified.

CONCLUSION: Rimegepant 75 mg oral tablet was effective in the acute treatment of migraine. Tolerability and safety were similar to placebo, with no evidence of hepatotoxicity.

TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03235479.

PMID:39070853 | PMC:PMC11277999 | DOI:10.2147/JPR.S453806

Clinics (Sao Paulo). 2024 Jul 27;79:100449. doi: 10.1016/j.clinsp.2024.100449. eCollection 2024.

ABSTRACT

BACKGROUND: There is no gold-standard trigger for detecting drug-induced respiratory disorders, a type of Adverse Drug Event (ADE) with high morbimortality, particularly in older people.

OBJECTIVE: To propose and evaluate the performance of triggers for detecting hospitalizations related to drug-induced respiratory disorders in older people.

METHODS: A pilot cross-sectional study was conducted with older people (age ≥ 60) admitted to a Brazilian hospital. Electronic chart documentation was screened using ICD-10 codes; Global Trigger Tool (GTT); and drugs potentially associated with respiratory disorders. A chart and medication review were conducted to perform the causality assessment using the instrument developed by the World Health Organization. The performance of triggers was evaluated by the Positive Predictive Value (PPV), with values ≥ 0.20 indicating good performance.

RESULTS: Among 221 older people, 72 were eligible. Potential drug-induced dyspnea and/or cough were detected in six older people (6/72), corresponding to a prevalence of 8.3 %. The overall PPV of the triggers was 0.14, with abrupt medication stop (PPV = 1.00), codeine (PPV = 1.00), captopril (PPV = 0.33), and carvedilol (PPV = 0.33) showing good performance. Two triggers were proposed for detecting therapeutic ineffectiveness associated with respiratory disorders: furosemide (PPV = 0.23) and prednisone (PPV = 0.20).

CONCLUSION: The triggers enabled the identification that one in 12 hospitalizations was related to drug-induced respiratory. Although good performance was observed in the application of triggers, additional investigations are needed to assess the feasibility of incorporating them into clinical practice for the screening, detection, management, and reporting of these ADEs, which are considered to be underreported and difficult to detect.

PMID:39068723 | DOI:10.1016/j.clinsp.2024.100449

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2291-2295. doi: 10.31557/APJCP.2024.25.7.2291.

ABSTRACT

BACKGROUND: Fatigue is an immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs) used for cancer treatment. Chinese herbal medicines (Ho-zai) are used to treat cancer-related fatigue. However, no interactions between ICIs and Ho-zai have been reported. Herein, we investigated the risk of irAEs associated with the concomitant use of ICIs and Ho-zai.

METHODS: We extracted data of patients who used ICI and Ho-zai from the Japanese Adverse Event Reporting Database. The proportional reporting ratio (PRR) was calculated for patients using ICI, Ho-zai, or both. We focused on cases of interstitial lung disease (ILD) and colitis, which were among the most severe cases of irAEs among these patients. The shrinkage method used by the World Health Organization-Uppsala Monitoring Center was used to detect the interactions.

RESULTS: Of the 799,670 patients in the database, 77,219, 2060, and 92 were using ICIs, Ho-zai, and combination treatment, respectively. The ILD and colitis groups included 39,388 and 17,522 patients, respectively. ILD signals were detected for both ICIs and Ho-zai. There were 24 cases of patients treated with concomitant ICIs and Ho-zai who developed ILD. For all combinations of all ICIs and all Ho-zai, Ω025 was negative, which suggested no ILD-related interactions. Colitis signals were detected for ICIs except for atezolizumab, avelumab, and durvalumab. There were eight patients treated with concomitant ICI and Ho-zai who developed colitis. For all combinations of all ICIs and all Ho-zai, Ω025 was negative, which suggested no colitis-related interactions.

CONCLUSION: To our knowledge, this is the first study to investigate interactions between ICIs and Ho-zai. Signals were detected for ILD in both ICI and Ho-zai groups, and colitis in the ICI group. However, the combined use of these treatments did not increase the risk of irAEs.

PMID:39068560 | DOI:10.31557/APJCP.2024.25.7.2291

J Hematol Oncol. 2024 Jul 27;17(1):54. doi: 10.1186/s13045-024-01581-2.

ABSTRACT

Cancer immunotherapies, represented by immune checkpoint inhibitors (ICIs), have reshaped the treatment paradigm for both advanced non-small cell lung cancer and small cell lung cancer. Programmed death receptor-1/programmed death receptor ligand-1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are some of the most common and promising targets in ICIs. Compared to ICI monotherapy, which occasionally demonstrates treatment resistance and limited efficacy, the dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 operates at different stages of T cell activation with synergistically enhancing immune responses against cancer cells. This emerging dual therapy heralds a new direction for cancer immunotherapy, which, however, may increase the risk of drug-related adverse reactions while improving efficacy. Previous clinical trials have explored combination therapy strategy of anti-PD-1/PD-L1 and anti-CTLA-4 agents in lung cancer, yet its efficacy remains to be unclear with the inevitable incidence of immune-related adverse events. The recent advent of bispecific antibodies has made this sort of dual targeting more feasible, aiming to alleviate toxicity without compromising efficacy. Thus, this review highlights the role of dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in treating lung cancer, and further elucidates its pre-clinical mechanisms and current advancements in clinical trials. Besides, we also provide novel insights into the potential combinations of dual blockade therapies with other strategies to optimize the future treatment mode for lung cancer.

PMID:39068460 | DOI:10.1186/s13045-024-01581-2

Indian J Tuberc. 2024;71 Suppl 1:S97-S100. doi: 10.1016/j.ijtb.2024.06.001. Epub 2024 Jun 10.

ABSTRACT

BACKGROUND: It is estimated that drug-resistant (DR) Tuberculosis (TB) (DR-TB) patients in Indonesia are 2.40% of all new TB patients and 13% of previously treated TB patients with a total incidence of DR-TB cases of 24,000 people. The adverse drug reactions (ADRs) of DR-TB are still a problem that can certainly affect the success of therapy. The aim of this study was to determine the correlation between the length of therapy and regimen therapy of DR-TB with the severity of ADRs.

METHODS: Data collection was carried out retrospectively on the medical records of DR-TB patients in 2020-2021 and sampling used a purposive sampling technique that complied with the inclusion criteria.

RESULTS: Of the 86 patients, the majority of DR-TB patients in X Hospital were 26-45 years old 35 (40.7%), 52 (60.5%) male, the most common comorbid was type II DM, 19 (22.1%), and the most nutritional status was malnutrition as much as 39 (45.3%). The most common type of ADR was hyperuricemia in 31 (36.0%). The results of the correlation analysis showed that there was a relationship between the length of therapy and the severity of ADRs (ρ = 0.002) and there was no relationship between the type of therapy regimen and the severity of ADRs (ρ = 0.184).

CONCLUSION: The longer DR-TB therapy, the higher the severity of ADRs and there is no relationship between the type of therapy regimen and the severity of ADRs.

PMID:39067964 | DOI:10.1016/j.ijtb.2024.06.001

Indian J Tuberc. 2024;71 Suppl 1:S25-S28. doi: 10.1016/j.ijtb.2023.06.001. Epub 2023 Jun 7.

ABSTRACT

This study is conducted from year 2019-2022 in Gujarat Cancer Society medical college and research center, Ahmedabad. Out of total 275 patients on drug resistant TB regimen (all oral longer, shorter injectable and mono H) seen in opd, 55 patients presented with adverse drug reaction. Most commonly affected age group was 20-40 yr old. During the course of treatment 32.7% required hospitalization, of which 29% were admitted in ward, rest required ICU care. Maximum ADR occurred in first 30 days of starting ATT. Drug had to be withdrawn in 41.81% and in 32.7%, offending agent was withdrawn permanently. There was no mortality during the study.

PMID:39067950 | DOI:10.1016/j.ijtb.2023.06.001

Indian J Tuberc. 2024;71 Suppl 1:S136-S140. doi: 10.1016/j.ijtb.2024.03.002. Epub 2024 Mar 6.

ABSTRACT

BACKGROUND: Pharmacovigilance entails monitoring of patients for timely detection of ADR and reporting them so that more information about drug safety can be obtained. This may help in the future for dose modification or alteration of regimen. In NTEP, ADSm (Active Drug Safety monitoring) is part of pharmacovigilance. In this study we shall be studying ADRs to Anti TB drugs in DRTB.

METHODOLOGY: This study is observational, retrospective and record based, of patients admitted from 2021 to 2023 in the DOTS ward of Respiratory Medicine Department of a tertiary care hospital in Goa. Data such as age, sex, regimen, date of AKT initiation and adverse effects documented has been noted and compiled.

RESULTS: ADRs have been tabulated in the form of tables. Statistical analysis is done to find out the commonest ADR, time when they are likely to occur, which age and gender are most likely affected and if there are any other associated risk factors for ADRs.

CONCLUSION: This study will enable in future to better monitor patients with regard to particular adverse drug reaction, patient safety and if needed to alter the regimen as early as possible.

PMID:39067945 | DOI:10.1016/j.ijtb.2024.03.002

Indian J Tuberc. 2024;71 Suppl 1:S110-S116. doi: 10.1016/j.ijtb.2023.04.011. Epub 2023 Apr 11.

ABSTRACT

World Health Organization (WHO) issued the latest recommendations regarding the management of drug-resistant Tuberculosis (TB) in 2022, allowing the replacement of ethambutol (6 months) with linezolid (2 months). This recommendation also introduced a new regimen, namely bedaquiline, pretomanide, linezolid, moxifloxacin (BPaLM) for fluoroquinolone-sensitive patients and bedaquiline, pretomanide, linezolid, (BPaL) for patients insensitive to fluoroquinolone (6-9 months). The latest TB regimen introduced by WHO provides a shorter-course treatment, however not much has been discussed about the impact of this new regimen on chronic kidney disease (CKD) patients, particularly on hemodialysis (HD). The condition of CKD can interfere with the pharmacokinetics of TB medication, thus could reduce effectiveness and increase toxicity. The drugs used on this new regimen are mostly safe for renal impairment patients due to the dominant metabolism in the liver. Particular precaution is given to the administration of linezolid due to increased hematology side effects and bedaquiline with the side effect of QTC interval lengthening and increased risk of arrhythmias. Although this regimen research has not been in many studies in renal failure patients, no significant side effects nor kidney damage evidence was found. This remains to be proven by more research on the patient population with renal failure.

PMID:39067942 | DOI:10.1016/j.ijtb.2023.04.011

Indian J Tuberc. 2024;71 Suppl 1:S101-S109. doi: 10.1016/j.ijtb.2023.04.006. Epub 2023 Apr 10.

ABSTRACT

BACKGROUND: Monitoring and managing adverse drug reactions (ADR) are critical for treating drug-resistant tuberculosis (TB).

OBJECTIVE: To study symptomatic, linezolid-attributable ADRs in TB patients initiated on all oral longer bedaquiline-based treatment regime for multidrug-resistant/rifampicin-resistant (MDR/RR)-TB under programmatic conditions.

METHODS: It was a multicenter, retrospective study of people with MDR/RR-TB in nine TB units in Nagpur, India, from March 2020 to April 2022.

RESULTS: The study consisted of a sample size of 106 individuals with multidrug-resistant and rifampicin-resistant tuberculosis out of a total of 110 individuals with the disease. Of these, 45 (42.45%) experienced linezolid ADRs, with an incidence of 11.37 cases per 1000 person-weeks. These patients were significantly younger (31.24 ± 11.13 years) and more likely to be female (27, 50%) than those without ADRs. ADR severity was mild in 20 (44.45%), moderate in 15 (33.33%), and severe in 10 (22.22%) patients. The most common ADR was peripheral neuropathy (42, 93.33%), followed by lactic acidosis (3, 6.67%), anemia (2, 4.44%), and optic neuritis (2, 4.44%). Dosing was reduced in 17 (37.78%) patients, and linezolid was withdrawn entirely in 19 (42.22%) patients. Only 9 (20%) patients continued linezolid unmodified. For mild to moderate linezolid-associated symptomatic peripheral neuropathy, symptom management with or without dose reduction is an effective strategy; however, immediate linezolid withdrawal is necessary in severe or life-threatening peripheral neuropathy cases. After a mean follow-up of 41 ± 21.33 weeks, ADR symptoms resolved completely in 4 (6.67%) patients and decreased in 42 (93.33%) patients.

CONCLUSION: Linezolid ADRs, often neuropathy, frequently occur in patients on an all-oral bedaquiline-based treatment regime for MDR/RR-TB. Women and younger patients are more likely to experience these ADRs, usually mild to moderate in severity. Management of symptomatic linezolid-associated peripheral neuropathy should be based on ADR severity. These ADRs often affect linezolid dosing, so it is important to identify and manage them early.

PMID:39067941 | DOI:10.1016/j.ijtb.2023.04.006

Medicina (Kaunas). 2024 Jul 12;60(7):1123. doi: 10.3390/medicina60071123.

ABSTRACT

Background and Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing pathology with significant clinical consequences, including increased cardiovascular risk and cognitive decline. Continuous positive airway pressure (CPAP) is the gold-standard treatment, but alternative strategies are sometimes needed for patients intolerant to CPAP. Drug-induced sleep endoscopy (DISE) is a key diagnostic tool for assessing upper airway obstruction in OSA patients and subsequently tailoring a surgical approach, with sedation protocols playing a crucial role in its efficacy and results accuracy. This study aimed to investigate the effect of adding remifentanil to a propofol target-controlled infusion (TCI) regimen on the sedation parameters and procedural outcomes of DISE. Materials and Methods: The study was conducted at the Central University and Emergency Military Hospital "Dr. Carol Davila" and Ria Clinic in Bucharest between July 2021 and October 2023. Thirty-one patients were enrolled and randomised into two groups: a propofol group (P group, n= 11) and a remifentanil-propofol group (R-P group, n = 20). DISE was performed using standardised protocols, sedative drugs were administered in TCI mode, and data on sedation levels, respiratory and cardiovascular parameters, and procedural incidents were collected. Results: The addition of remifentanil at 1 ng/mL effect-site concentration significantly reduced the effect-site concentration of propofol required for adequate sedation (3.4 ± 0.7 µg/mL in the P group vs. 2.8 ± 0.6 µg/mL in the R-P group, p = 0.035). The time to achieve adequate sedation was also shorter in the R-P group (7.1 ± 2.5 min vs. 9.5 ± 2.7 min, p = 0.017). The incidence of cough, hypoxemia, and cardiovascular events did not significantly differ between the two groups. Conclusions: Adding remifentanil to a propofol TCI regimen for DISE effectively reduces the required propofol effect-site concentration and shortens sedation time without increasing the risk of adverse events. This combination may enhance the safety and efficiency of DISE, offering a promising alternative for patients undergoing this procedure.

PMID:39064552 | DOI:10.3390/medicina60071123

Medicina (Kaunas). 2024 Jul 3;60(7):1092. doi: 10.3390/medicina60071092.

ABSTRACT

Triple-negative breast cancer (TNBC) represents a challenging malignancy with limited treatment options and a poor prognosis. Adjuvant therapies, including chemotherapy and immune checkpoint inhibitors (ICI), are commonly employed following breast conservation surgery. However, these treatments can lead to various adverse effects, including cutaneous complications and connective tissue disorders. Here, we present the case of a 54-year-old woman with TNBC who developed morphea, a form of localized scleroderma, following adjuvant chemotherapy and pembrolizumab administration. This case highlights the rarity of drug-induced morphea and emphasizes the importance of recognizing and managing such adverse events in breast cancer patients. We discuss the clinical characteristics, diagnostic challenges, and treatment considerations associated with drug-induced scleroderma-like lesions, as well as the potential mechanisms underlying their development. Furthermore, we review the literature on the incidence, clinical features, and outcomes of scleroderma-like lesions induced by chemotherapy and ICIs. This case underscores the need for increased awareness of immune-related adverse events in patients receiving immunotherapy, as well as the importance of individualized treatment approaches to optimize patient care and outcomes.

PMID:39064521 | DOI:10.3390/medicina60071092