Lung Cancer. 2024 Dec 18;199:108054. doi: 10.1016/j.lungcan.2024.108054. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). This study investigates the relationship between CT-assessed sarcopenia and irAEs in patients with lung cancer who are receiving ICIs.

METHODS: Patients were enrolled if they had lung cancer treated with ICIs at the University Medical Center Groningen (2015-2021) and had undergone low-dose CT scans that included the third lumbar vertebral level (L3). CT-assessed sarcopenia was defined based on reported L3 skeletal muscle mass index (L3SMI) thresholds. Patients were categorized into no, any-grade, and severe irAE groups. The association between CT-assessed sarcopenia and irAEs was assessed by competing risk time-to-event analysis, accounting for the risk of death. Sub-distribution hazard ratios (SDHR) were calculated using Fine-Gray regression models adjusted for relevant confounders. The association between CT-assessed sarcopenia and overall survival (OS) was evaluated through survival analyses.

RESULTS: We included 363 patients; most were male (60.9 %), had favorable Eastern Cooperative Oncology Group (ECOG) performance statuses (0-1; 90.1 %), had stage IV disease (92.8 %), and received ICI monotherapy (82.9 %). Of these, 45.6 % developed any-grade irAEs and 21 % developed severe irAEs. Endocrine disorders were the most common mild irAEs (24.8 %), while respiratory disorders were the most common severe irAEs (24.7 %). CT-assessed sarcopenia was more prevalent in the no irAE group (87 %) compared with the any-grade (77 %) and severe (79 %) irAE groups. Presence of CT-assessed sarcopenia was associated with a lower risk of developing any irAEs (SDHR = 0.62 [95 % CI: 0.41-0.92]). No significant association was found between CT-assessed sarcopenia and severe irAEs (fully adjusted model, SDHR = 0.74 [95 % CI: 0.39-1.4]), or between CT-assessed sarcopenia and OS.

CONCLUSION: CT-assessed sarcopenia is associated with a reduced risk of any irAEs in patients with lung cancer receiving ICIs, possibly because higher muscle mass enhances the host response to immunological stimulation. Recognizing sarcopenia as a predictive factor for irAEs is relevant for personalizing treatments.

PMID:39708387 | DOI:10.1016/j.lungcan.2024.108054

Cancer Immunol Immunother. 2024 Dec 21;74(1):30. doi: 10.1007/s00262-024-03871-7.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are an important therapeutic pillar in metastatic urothelial carcinoma (mUC). The occurrence of immune-related adverse events (irAEs) appears to be associated with improved outcomes in observational studies. However, these associations are likely affected by immortal time bias and do not represent causal effects. The aim of this study was to assess the effect of irAEs on outcomes while correcting for immortal time bias, using target trial emulation (TTE).

METHODS: TTE was contrasted to adjusted naïve and time-updated Cox models. We performed a multi-institutional retrospective study involving mUC patients under ICI. The primary objective was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Secondary endpoints included the influence of irAEs on objective response rates (ORRs) to ICI and the influence of systemic corticosteroids on outcomes.

RESULTS: Among 335 patients (median age: 69 yrs), 69.6% received ICI in the second line or further lines. During a median follow-up of 21.1 months, 122 (36.4%) patients developed irAEs of any grade (grade ≥ 3: 14.9%). Hazard ratios (HRs) for PFS ranged from 0.37 for naïve adjusted Cox model to 0.88 (95% confidence interval (CI), 0.59-1.30) with time-updated covariates, and from 0.41 to 1.10 (95% CI, 0.69-1.75) for OS. TTE accounting for immortal time bias yielded a HR of 1.02 (95% CI, 0.72-1.44) for PFS, and 0.90 (95% CI, 0.62-1.30) for OS. In contrast to the naïve Cox model (HR = 2.26, 95% CI 1.26-4.05), the presence of irAEs was no longer a predictive factor for improved ORR in time-updated Cox models (HR = 1.27, 95% CI 0.68-2.36) and TTE (HR = 1.43, 95% CI 0.89-2.29). In patients with irAEs, systemic corticosteroids did not negatively impact survival.

CONCLUSION: Using TTE, we were able to show that the occurrence of irAEs is no longer associated with better survival or improved response rates to ICI in mUC patients, in contrast to the naïve analysis. These findings demonstrate that TTE is a suitable formal framework to avoid immortal time bias in studies with time-dependent non-interventional exposures.

PMID:39708183 | DOI:10.1007/s00262-024-03871-7

BMC Med Res Methodol. 2024 Dec 20;24(1):312. doi: 10.1186/s12874-024-02443-8.

ABSTRACT

BACKGROUND: Liver injury from drug-drug interactions (DDIs), notably with anti-tuberculosis drugs such as isoniazid, poses a significant safety concern. Electronic medical records contain comprehensive clinical information and have gained increasing attention as a potential resource for DDI detection. However, a substantial portion of adverse drug reaction (ADR) information is hidden in unstructured narrative text, which has yet to be efficiently harnessed, thereby introducing bias into the research. There is a significant need for an efficient framework for the DDI assessment.

METHODS: Using a Chinese natural language processing (NLP) model, we extracted 25,130 adverse drug reaction (ADR) records, dividing them into sets for training an automated normalization model. The trained models, in conjunction with liver function laboratory tests, were used to thoroughly and efficiently identify liver injury cases. Ultimately, we applied a case-control study design to detect DDI signals increasing isoniazid's liver injury risk.

RESULTS: The Logistic Regression model demonstrated stable and superior performance in classification task. Based on laboratory criteria and NLP, we identified 128 liver injury cases among a cohort of 3,209 patients treated with isoniazid. Preliminary screening of 113 drug combinations with isoniazid highlighted 20 potential signal drugs, with antibacterials constituting 25%. Sensitivity analysis confirmed the robustness of signal drugs, especially in cardiac therapy and antibacterials.

CONCLUSION: Our NLP and machine learning approach effectively identifies isoniazid-related DDIs that increase the risk of liver injury, identifying 20 signal drugs, mainly antibacterials. Further research is required to validate these DDI signals.

PMID:39707270 | DOI:10.1186/s12874-024-02443-8

Blood Cancer J. 2024 Dec 20;14(1):223. doi: 10.1038/s41408-024-01206-4.

ABSTRACT

Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare. This study utilized the openFDA human drug adverse events (AEs) to analyze global data pertaining to MM patients and patterns of treatment-related AEs. We identified ten most frequently used drugs and drug regimens in six distinct regions, including North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America & the Caribbean (LA). AE patterns were evaluated using the reporting odds ratio combined with a 95% confidence interval. AE reports were more prevalent in men than in women across all regions. Cardiotoxicities were more likely observed in AS and EU, while secondary neoplasms were more frequently reported in the EU. Nephropathies were prominent in OC, AF (in males), and AS (in females), while vascular toxicity, including embolism and thrombosis, was more common in NA (in males). A notable improvement in survival, particularly in AS, EU, and NA, with a significant decline in death rates was observed. Hospitalization rates displayed less variation in AS and EU but exhibited more pronounced fluctuations in AF, LA, and OC. In conclusion, this comprehensive analysis offers valuable insights into the demographic, geographic, and AE patterns of MM patients across the globe.

PMID:39706832 | DOI:10.1038/s41408-024-01206-4

JMIR Infodemiology. 2024 Dec 20;4:e53424. doi: 10.2196/53424.

ABSTRACT

BACKGROUND: Spontaneous pharmacovigilance reporting systems are the main data source for signal detection for vaccines. However, there is a large time lag between the occurrence of an adverse event (AE) and the availability for analysis. With global mass COVID-19 vaccination campaigns, social media, and web content, there is an opportunity for real-time, faster monitoring of AEs potentially related to COVID-19 vaccine use. Our work aims to detect AEs from social media to augment those from spontaneous reporting systems.

OBJECTIVE: This study aims to monitor AEs shared in social media and online support groups using medical context-aware natural language processing language models.

METHODS: We developed a language model-based web app to analyze social media, patient blogs, and forums (from 190 countries in 61 languages) around COVID-19 vaccine-related keywords. Following machine translation to English, lay language safety terms (ie, AEs) were observed using the PubmedBERT-based named-entity recognition model (precision=0.76 and recall=0.82) and mapped to Medical Dictionary for Regulatory Activities (MedDRA) terms using knowledge graphs (MedDRA terminology is an internationally used set of terms relating to medical conditions, medicines, and medical devices that are developed and registered under the auspices of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use). Weekly and cumulative aggregated AE counts, proportions, and ratios were displayed via visual analytics, such as word clouds.

RESULTS: Most AEs were identified in 2021, with fewer in 2022. AEs observed using the web app were consistent with AEs communicated by health authorities shortly before or within the same period.

CONCLUSIONS: Monitoring the web and social media provides opportunities to observe AEs that may be related to the use of COVID-19 vaccines. The presented analysis demonstrates the ability to use web content and social media as a data source that could contribute to the early observation of AEs and enhance postmarketing surveillance. It could help to adjust signal detection strategies and communication with external stakeholders, contributing to increased confidence in vaccine safety monitoring.

PMID:39705077 | DOI:10.2196/53424

Monaldi Arch Chest Dis. 2024 Dec 19. doi: 10.4081/monaldi.2024.3181. Online ahead of print.

ABSTRACT

The N-acetyltransferase 2 (NAT2) gene exhibits substantial genetic diversity, leading to distinct acetylator phenotypes among individuals. In this study, we determine NAT2 gene polymorphisms in tuberculosis (TB) patients and analyze serum isoniazid (INH) concentrations across the various genotypes. An observational prospective cohort study involving 217 patients with pulmonary or extrapulmonary TB was carried out. The NAT2 genotypes were identified using real-time polymerase chain reaction technology. INH concentrations at baseline and 2 hours post-dosing were estimated using high-performance liquid chromatography. The association between the acetylator status and INH concentrations was evaluated using odds ratios (OR) and the occurrence of adverse events across the different patient genotypes was also assessed. The genotype frequency of fast, intermediate, and slow acetylators was 7.37%, 39.17%, and 53.46%, respectively, while allele frequency was 27% for fast acetylators and 73% for slow acetylators. All the alleles followed the Hardy-Weinberg equilibrium. Patients with slow acetylator status had significantly increased serum INH concentrations 2 hours post-drug administration, followed by intermediate acetylators as compared to fast acetylators. 69 (31.8%) patients developed adverse drug reactions post-therapy. Patients with slow acetylator status had the highest (OR: 9.66) risk of developing drug-induced hepatoxicity, especially those with raised serum INH concentrations (OR: 1.34). Understanding the correlation between genetics and serum antitubercular drug levels in antitubercular drug-induced hepatotoxicity will provide valuable information to the medical community, minimizing the risk of adverse reactions and hospitalizations.

PMID:39704240 | DOI:10.4081/monaldi.2024.3181

Int J Clin Pharm. 2024 Dec 19. doi: 10.1007/s11096-024-01847-2. Online ahead of print.

ABSTRACT

BACKGROUND: The application of digital technologies has shown benefits in enhancing pharmacovigilance activities but consumers views on the use of these tools for this purpose are not well described.

AIM: To explore consumers' views on using digital tools to report adverse drug reactions (ADRs) and identify key features that consumers want in digital tools for ADR reporting.

METHOD: An online survey was conducted among adults who had taken medicine in the previous six-months in Australia. The development of questions was guided by the Combined Technology Acceptance Model and Theory of Planned Behaviour (C-TAM-TPB) framework. Responses to closed-ended questions were analysed using descriptive statistics and chi-square/Fisher's exact test, while free-text responses were analysed using qualitative content analysis.

RESULTS: A total of 494 responses were included in the analysis. Eighty-seven percent of respondents preferred using digital tools for reporting ADRs. Consumers indicated a free-text space for describing ADRs (90%) as important or very important features of digital tools for ADR reporting, followed by acknowledgement of their report submission (87%) and receiving summary of previously reported ADRs (87%). Women (p < 0.001), advanced smartphone users (p < 0.001), and previous digital healthcare tool users (p = 0.017) showed higher intention to use digital tools. Consumers emphasized the importance of ease-of-use, accessibility, receiving medicine safety information, feedback, and advice for reporting ADRs via digital tools.

CONCLUSION: Consumers prefer using digital tools for reporting ADRs and place high value on features such as a free-text space for describing ADRs, acknowledgement of report submissions, and access to summaries of previously submitted reports.

PMID:39699849 | DOI:10.1007/s11096-024-01847-2

Neurotox Res. 2024 Dec 19;43(1):2. doi: 10.1007/s12640-024-00724-0.

ABSTRACT

Chronic use of typical antipsychotics can lead to varying motor effects depending on the timing of analysis. Acute treatment typically induces hypokinesia, resembling parkinsonism, while repeated use can result in tardive dyskinesia, a hyperkinetic syndrome marked by involuntary orofacial movements, such as vacuous chewing movements in mice. Tardive dyskinesia is particularly concerning due to its potential irreversibility and associated motor discomfort. One prevailing theory suggests that tardive dyskinesia arises from hypersensitivity of D2-type dopaminergic receptors caused by continuous blockade from typical antipsychotics like haloperidol. Additionally, increased inflammation, oxidative stress, and elevated FosB protein expression in the dorsolateral striatum are implicated in its pathophysiology. Current treatments for tardive dyskinesia often lack clear efficacy and may lead to significant side effects. Cannabigerol, a non-psychotomimetic cannabinoid with antioxidant and anti-inflammatory properties, has been investigated for its potential antidyskinetic effects. In this study, mice were treated with cannabigerol at doses of 3 and 10 mg/kg to evaluate its ability to prevent, ameliorate, or reverse haloperidol-induced vacuous chewing movements. Cannabigerol successfully reduced vacuous chewing movements without affecting normal motor activity, exacerbating haloperidol-induced hypokinesia, or inducing dyskinetic effects on its own. However, no significant reversal of the haloperidol-induced motor effects was observed under the current protocol. Furthermore, cannabigerol did not alter FosB expression or microglia morphology. These findings underscore the need for further research to explore cannabigerol's therapeutic potential and contribute to our understanding of its possible clinical applications in managing tardive dyskinesia.

PMID:39699828 | DOI:10.1007/s12640-024-00724-0

Rev Panam Salud Publica. 2024 Dec 18;48:e106. doi: 10.26633/RPSP.2024.106. eCollection 2024.

ABSTRACT

OBJECTIVE: To describe the process of restructuring the National Expert Committee and its impact on the causality assessment of events supposedly attributable to vaccination or immunization (ESAVI) in the context of vaccine safety monitoring during the COVID-19 pandemic, 2020-2023.

METHOD: A report was prepared on the experience of creating and operating Mexico's National Expert Committee during the aforementioned period.

RESULTS: During the 2020-2023 period, 1293 severe ESAVIs were reported after COVID-19 vaccination; after 98.6% (1275) of them had been assessed and classified, 10 specialized subcommittees were formed.

CONCLUSIONS: Restructuring of the committee, assessment of adverse events with a series of prior steps, and use of the World Health Organization's causality assessment tool made it possible to generate scientific documents to validate vaccine safety and maintain trust in vaccination.

PMID:39697271 | PMC:PMC11653959 | DOI:10.26633/RPSP.2024.106

Mod Rheumatol. 2024 Dec 19:roae114. doi: 10.1093/mr/roae114. Online ahead of print.

ABSTRACT

OBJECTIVES: Onco-rheumatology, the intersection of oncology and rheumatology, is an emerging field requiring further definition. This study aimed to identify the knowledge and skills essential for rheumatologists in clinical oncology.

METHODS: We retrospectively reviewed consultations with the onco-rheumatology department of a high-volume tertiary cancer centre in Japan from January 2020 to December 2023.

RESULTS: We analysed 417 consultations. The most common consultation (229, 55%) was related to immune checkpoint inhibitor-induced immune-related adverse events (irAEs). Of the 238 irAEs in 185 patients, 15% were rheumatic and 85% were non-rheumatic (e.g., hepatobiliary toxicities, colitis). Approximately 25% of non-endocrine irAEs were refractory/relapsing, requiring second-line therapy (e.g., mycophenolate mofetil, biologics, immunoglobulin). In addition to irAE consultations, 137 (33%) consultations were about possible rheumatic diseases. The final diagnosis often related to cancer treatment, such as granulocyte colony-stimulating factor-related aortitis (15 patients, 11%), olaparib-related erythema nodosum (10 patients, 7.3%), and surgical menopause-related arthralgia (10 patients, 7.3%). Five patients (3.6%) were diagnosed with autoinflammatory bone disease mimicking bone tumours.

CONCLUSIONS: Onco-rheumatologists are expected to play a central role in the management of a wide range of irAEs, not limited to rheumatic irAEs. They must also manage rheumatologic manifestations during cancer treatment and rheumatic diseases that mimic tumours.

PMID:39697136 | DOI:10.1093/mr/roae114

Pharmacoepidemiol Drug Saf. 2024 Dec;33(12):e70072. doi: 10.1002/pds.70072.

ABSTRACT

PURPOSE: The underreporting of adverse drug reactions (ADRs) remains a significant challenge in the Philippines. Pharmacists play a crucial role in ensuring medication safety, improving patient outcomes, and enhancing the overall effectiveness of pharmacovigilance (PV) systems. This study explored the barriers and facilitators affecting PV practices among pharmacists in Metro Manila.

METHODS: This study employed qualitative research through in-depth interviews using a semi-structured topic guide. Researchers interviewed pharmacists until data saturation was reached, where no new insights emerged. Qualitative data were analyzed inductively, utilizing Braun and Clarke's thematic analysis to identify key themes. MAXQDA was used to facilitate coding and analyzing the qualitative data.

RESULTS: A total of 40 pharmacists (72.5% female) participated in this study, evenly distributed across various practice areas and geographic locations in Metro Manila. The analysis identified four main themes related to pharmacists' nonreporting of ADRs: competency gaps, organizational challenges, reporting issues, and workplace constraints. Pharmacists' limited knowledge of ADRs and lack of experience in ADR reporting appear to be the primary barriers, along with environmental factors. Conversely, critical strategies for improving ADR notifications include capacity building, motivation and rewards, and work optimization.

CONCLUSION: Pharmacists recognize the importance of reporting ADRs and view it as a professional responsibility. By prioritizing knowledge enhancement, training, and system improvements, the identification and reporting of ADRs can be strengthened, ultimately enhancing patient safety and PV practices. This positive attitude toward ADR reporting lays the groundwork for interventions designed to overcome barriers and promote a culture of active reporting among pharmacists.

PMID:39696899 | DOI:10.1002/pds.70072

BMC Pharmacol Toxicol. 2024 Dec 18;25(1):97. doi: 10.1186/s40360-024-00821-y.

ABSTRACT

BACKGROUND: In the past few years, an increasing number of research studies have documented the utilization of durvalumab in the field of immunotherapy for cancerous tumors. However, there remains insufficient documentation regarding its associated adverse event (AEs). In order to enhance our comprehension of its toxicological profile, this investigation retrospectively examined the AEs linked to durvalumab using data from the US Food and Drug Administration adverse event reporting system (FAERS).

METHODS: Using data from FAERS for the period 2004 to 2024, the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and mu-item gamma Poisson shrinker (MGPS) four algorithms were used to quantify durvalumab related AEs. SAS 9.4 was used for statistical analysis.

RESULTS: We collected nonduplicated reported 17,629,340 patients from the FAERS database and 19,709 AEs cases in the target population with durvalumab as the primary drug of suspicion. There were 6 significantly disproportionate preferred terms (PTs) that fit all four algorithms simultaneously. The AEs commonly reported include death, radiation pneumonitis, pneumonitis, and lung disorders. Furthermore, durvalumab has been associated with additional AEs, such as metastases to the central nervous system and drug-induced liver injury.

CONCLUSIONS: The study revealed that durvalumab immunotherapy is associated with AEs including death, radiation pneumonitis, pneumonitis, metastases to the central nervous system, lung disorder and drug-induced liver injury. In clinical practice, it is crucial to be vigilant and prevent the occurrence of these AEs.

PMID:39696525 | DOI:10.1186/s40360-024-00821-y

BMC Cancer. 2024 Dec 18;24(1):1541. doi: 10.1186/s12885-024-13220-7.

ABSTRACT

OBJECTIVE: The potential of immune-related adverse events (irAEs) in predicting the efficacy of PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) has rarely been assessed. This study investigated the associations between irAEs and the clinical efficacy of PD-1 inhibitors combination therapy in patients with advanced NSCLC.

METHODS: A retrospective analysis was conducted of 73 patients with advanced NSCLC receiving PD-1 inhibitors combination therapy from January 2022 and July 2023. Patients were divided into two cohorts: patients with irAEs and patients without irAEs. We conducted an analysis to investigate the impact of irAEs on these different clinical outcomes.

RESULTS: There were no significant differences observed in clinical characteristics between the two cohorts, except for smoking status (P = 0.011).The cohort with irAEs exhibited a higher objective response rate (ORR) and disease control rate (DCR) compared to the cohort without irAEs (ORR: 32.5% vs 12.1%, P = 0.040; DCR: 80.0% vs 48.5%, P = 0.010).Moreover, the median progression-free survival (PFS) and overall survival (OS) were significantly better in the cohort with irAEs compared to the cohort without irAEs (PFS: 12.4 months vs 6.8 months, P = 0.009; OS: not reached vs 18.3 months, P = 0.024). Additionally, the multivariate COX regression analysis revealed that mild irAEs (PFS: HR = 0.386, 95% CI: 0.199-0.748, P = 0.005; OS: HR = 0.300, 95% CI: 0.105-0.855, P = 0.024) and single-system irAEs (PFS: HR = 0.401, 95% CI: 0.208-0.772, P = 0.006; OS: HR = 0.264, 95% CI: 0.090-0.776, P = 0.015) were identified as independent prognostic factors for both PFS and OS.

CONCLUSIONS: IrAEs, especially thyroid irAEs, as well as mild or single-system irAEs, may serve as predictors of improved efficacy in advanced NSCLC patients receiving PD-1 inhibitors combination therapy.

PMID:39696102 | DOI:10.1186/s12885-024-13220-7

BMC Pulm Med. 2024 Dec 18;24(1):609. doi: 10.1186/s12890-024-03445-4.

ABSTRACT

BACKGROUND: UMEC/VI administered via a combination inhaler is associated with a clinically significant improvement in lung function and health-related quality of life in patients with mild-to-moderate COPD. However, their efficacy compared to other bronchodilator mono or dual therapies still remains unclear.

OBJECTIVE: The objective of this research was to evaluate the therapeutic efficacy of UMEC/VI dual and UMEC/VI/FF triple therapies versus alternative bronchodilator regimens in COPD patients.

METHODS: A systematic search was conducted using four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. The odds ratio (OR) and risk ratio (RR) was calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane Q and I [2] statistics and the appropriate p-value. The analysis used RevMan 5.4.

RESULTS: The current meta-analysis includes 31,814 COPD patients from 17 RCTs. The meta-analysis results demonstrate that the combination of LABA and LAMA provides additive bronchodilation and improved lung function in COPD patients. We found that UMEC/VI dual therapy significantly improved FEV1 (OR 1.98 [95% CI 1.70-2.30]), TDI values (OR 1.97 [95% CI 1.72-2.26]), and reduced SGRQ total scores (OR 1.99 [95% CI 1.71-2.32]), with fewer drug-related adverse events (RR 0.58 [95% CI 0.53-0.64]). Similarly, UMEC/VI/FF triple therapy also showed similar benefits, with significant improvements in FEV1 (OR 1.93 [95% CI 1.73-2.15]), TDI values (OR 2.37 [95% CI 2.15-2.61]), and reduced SGRQ total scores (OR 1.83 [95% CI 1.63-2.05]), and fewer drug-related adverse events (RR 0.53 [95% CI 0.49-0.58]).

CONCLUSION: This systematic review and meta-analysis concludes that UMEC and VI combinations are an efficacious treatment option for symptomatic COPD patients.

PMID:39696097 | DOI:10.1186/s12890-024-03445-4

BMC Health Serv Res. 2024 Dec 18;24(1):1564. doi: 10.1186/s12913-024-12015-7.

ABSTRACT

BACKGROUND: Vascular surgery patients are at a high risk of polypharmacy and drug-related problems. Only a limited number of studies have explored the impact of hospital pharmacists being members of a multidisciplinary team in the care of vascular surgery patients. The clinical study (Trial Registration Number NCT04930302, 16th June 2021) aimed to assess the impact of pharmacist-led interventions on the prevalence of drug-related problems among patients hospitalised at the vascular surgery department.

METHODS: The study, conducted at a specialised hospital in Slovakia during a 1-year period, included adult patients with carotid artery disease or lower extremity artery disease, taking ≥3 medications. Medication reconciliation and medication reviews were performed by hospital pharmacists at both admission and discharge. Pharmacist-proposed interventions were documented and communicated to the physician, patients were educated about their medications upon discharge.

RESULTS: Among our study participants (n = 105), the average number of drug-related problems at admission was 2.3 ± 2.1, significantly decreasing to 1.6 ± 1.8 at discharge (p < 0.001). The predominant drug classes associated with drug-related problems were those related to the cardiovascular system (41.9%). At admission, the most frequent drug-related problem was untreated indication (40.3%), mostly caused by the failure to prescribe statin in patients with lower extremity artery disease. The highest acceptance rate of pharmacist-led interventions was at hospital admission (66.1%). More than 50% of patients were classified as those with good understanding of their pharmacotherapy.

CONCLUSIONS: This study demonstrates that pharmacist-led interventions significantly reduce drug-related problems in vascular surgery patients during hospitalisation, contributing to patient safety and clinical outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Trial Registration Number: NCT04930302, 16th June 2021.

PMID:39695586 | DOI:10.1186/s12913-024-12015-7

BMC Med Inform Decis Mak. 2024 Dec 18;24(1):395. doi: 10.1186/s12911-024-02801-y.

ABSTRACT

BACKGROUND: Digital solutions can help monitor medication safety in children who are often excluded in clinical trials. The lack of reliable safety data often leads to either under- or over-dose of medications during clinical management which make them either not responding well to treatment or susceptible to adverse drug reactions (ADRs).

AIM: This study investigated ADR signalling techniques to detect serious ADRs in Malaysian children aged from birth to 12 years old using an electronic ADRs' database.

METHODS: Four techniques (Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS)) were tested on ADR reports submitted to the National Pharmaceutical Regulatory Agency between 2016 and 2020. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the techniques were compared.

RESULTS: A total of 31 medicine-Important Medical Event pairs were found and examined among the 3152 paediatric ADR reports. Three techniques (PRR, ROR, MGPS) signalled oculogyric crisis and dystonia for metoclopramide. BCPNN and MGPS signalled angioedema for paracetamol, amoxicillin and ibuprofen. Similar performances were found for PRR, ROR and BCPNN (sensitivity of 12%, specificity of 100%, PPV of 100% and NPV of 21%). MGPS revealed the highest sensitivity (20%) and NPV (23%), as well as similar specificity and PPV (100%).

CONCLUSIONS: This study suggests that medication safety signalling techniques could be applied on electronic health records to monitor medication safety issues in children. Clinicians and medication safety specialist could prioritise the signals for further clinical consideration and prompt response.

PMID:39695558 | DOI:10.1186/s12911-024-02801-y

BMC Cancer. 2024 Dec 18;24(1):1520. doi: 10.1186/s12885-024-13284-5.

ABSTRACT

BACKGROUND: Zoledronic acid (ZA) is widely used for the treatment of osteolytic bone metastases in malignancies and osteoporosis, but it has been associated with renal impairment. In this study, we investigated adverse events (AEs) related to renal and urinary system diseases associated with ZA using the U. S. FDA's Adverse Event Reporting System.

METHODS: We collected FAERS data from Q1 2004 to Q1 2024 and used the reporting odds ratio to detect AEs related to renal and urinary system diseases associated with ZA. Additionally, we applied multiple algorithms, including ROR, proportional reporting ratio, bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, to quantify renal and urinary AEs under different indications.

RESULTS: A total of 52,495 AE reports involving ZA as the primary suspect drug were identified. Among renal and urinary system diseases, 25 distinct AEs were recognized, with renal tubular necrosis being the most frequently reported. For different indications, renal tubular necrosis was the most reported AE in breast cancer and osteoporosis; nephrogenic diabetes insipidus was both the most frequent and strongest signal in lung cancer; proteinuria was most common in multiple myeloma, and polyuria in prostate cancer. Furthermore, most AEs occurred in patients who had been on ZA for more than 360 days, followed by those within the first 30 days of use.

CONCLUSION: Based on pharmacovigilance data from FAERS, different renal and urinary system AEs should be closely monitored and addressed according to the specific indications for which ZA is used.

PMID:39695477 | DOI:10.1186/s12885-024-13284-5

Eur J Hosp Pharm. 2024 Dec 18:ejhpharm-2024-004424. doi: 10.1136/ejhpharm-2024-004424. Online ahead of print.

NO ABSTRACT

PMID:39694632 | DOI:10.1136/ejhpharm-2024-004424

BMC Pregnancy Childbirth. 2024 Dec 18;24(1):819. doi: 10.1186/s12884-024-07027-4.

ABSTRACT

BACKGROUND: Breastfeeding is the most advantageous nutrition for infants because of its many health benefits. However, lactation insufficiency is a prevalent issue among women, particularly those who give birth prematurely. Galactagogues, such as domperidone and metoclopramide, have been reported and may be beneficial for lactation insufficiency. However, the optimal pharmacological galactagogue remains unclear.

METHODS: The PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases were searched from their inception to April 23, 2023. The primary aim of this research was to assess the efficacy and safety of domperidone and metoclopramide using Bayesian network meta-analysis. The efficacy outcome was the increased breast milk volume (in mL/day). The safety outcome was the frequency of maternal drug-related adverse events during the study period.

RESULTS: Seventeen randomized controlled trials were included in the final analyses. Preterm mothers who took domperidone had a greater increase in breast milk volume than those who took metoclopramide or placebo (domperidone vs. metoclopramide: MD = 82.84, 95% CI: 37.04-118.95; domperidone vs. placebo: MD = 88.30, 95% CI: 59.48-118.62). However, in the term mothers, domperidone did not show the above benefit compared with metoclopramide or placebo (domperidone vs. metoclopramide: MD = 93.67, 95% CI: -186.11-375.59; domperidone vs. placebo: MD = 126.25, 95% CI: -49.91-304.55). Both in preterm and term mothers, metoclopramide was no better than the placebo. There was no difference in the frequency of maternal drug-related adverse outcomes among domperidone, metoclopramide, and placebo.

CONCLUSION: Domperidone increased the daily breast milk volume in mothers of preterm infants, without serious adverse events. However, this conclusion is limited due to the small sample sizes in the studies analyzed.

PMID:39695450 | DOI:10.1186/s12884-024-07027-4

Beijing Da Xue Xue Bao Yi Xue Ban. 2024 Dec 18;56(6):1119-1125.

ABSTRACT

Systemic lupus erythematosus (SLE) is a diffuse, systemic autoimmune disorder that can impact multiple organs and systems, with patients exhibiting abnormal levels of various autoantibodies and immune markers in their serum. It is currently understood that dysregulation of B cells activation plays a pivotal role in the pathogenesis of SLE, as aberrantly activated B cells produce autoantibodies that inflict damage on multiple organs through complement activation and antibody-dependent cell-mediated cyto-toxicity. Traditional therapies for SLE may prove ineffective for certain patients or lead to adverse reactions. In most instances, conventional treatment merely alleviates symptoms and necessitates lifelong immunotherapy. A limited number of clinical cases have explored chimeric antigen receptor T cells (CAR-T) therapy as a potential treatment for autoimmune diseases such as SLE. Research indicates that CAR-T can specifically target CD19 expressed on the surface of B cells and plasma cells, achieving profound depletion while minimizing drug-related side effects. This report details a female patient diagnosed with SLE and lupus nephritis who was successfully treated using dual-targeting B cells maturation antigen CAR-T by our research team; following treatment, she ceased steroid and immunomodulator use, attaining sustained remission without these medications. The patient was a 23-year-old female. Multiple examinations in other hospitals and in our hospital showed positive anti-double-stranded DNA (dsDNA) antibody and low complement C3. Renal biopsy in our hospital showed lupus nephritis Ⅳ-G (A/C), and National Institutes of Health (NIH) activity index (AI) score=4. She was diagnosed with "SLE, lupus nephritis (LN)". She was treated with hormones, immunosuppressants and Chinese medicine, but the effect was not good. After the CAR-T treatment, She stopped using hormones and immune agents and achieved continuous remission with zero hormones and zero immune agents. She became pregnant six months after CAR-T infusion, and gave birth to a healthy full-term, full-weight baby successfully. She is the first patient in China who successfully discontinued hormone, immune preparations and gave birth after CAR-T therapy. During the follow-up of the patient, we found that the immune indexes had basically returned to normal, and the safety was good. It indicates that CAR-T therapy may represent a promising and innovative therapeutic approach for the management of SLE. This offers hope and establishes a precedent for SLE women of childbearing age.

PMID:39690781