Publications by authors named "Michael Sorich"

Intravenous midazolam is frequently used for procedural sedation. Use of ritonavir containing antivirals in patients requiring procedural sedation with intravenous midazolam is postulated to increase the risk or prolong the consequences of exposure related adverse events. The primary objective of this study was to characterize interaction of ritonavir with IV midazolam.

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Article Synopsis
  • - The study examined the individual participant data-sharing eligibility of clinical trials for the top 30 highest-revenue drugs approved by the FDA in 2021, finding that 64% of the 316 trials were eligible for sharing.
  • - Methods involved analyzing data from various sources and assessing key factors like trial phase and completion dates to determine the trials' data-sharing status.
  • - Results indicated higher eligibility rates for trials managed through independent data-sharing platforms and emphasized that trials not marked as completed had notably lower eligibility for data sharing.
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Importance: With the growing use of large language models (LLMs) in education and health care settings, it is important to ensure that the information they generate is diverse and equitable, to avoid reinforcing or creating stereotypes that may influence the aspirations of upcoming generations.

Objective: To evaluate the gender representation of LLM-generated stories involving medical doctors, surgeons, and nurses and to investigate the association of varying personality and professional seniority descriptors with the gender proportions for these professions.

Design, Setting, And Participants: This is a cross-sectional simulation study of publicly accessible LLMs, accessed from December 2023 to January 2024.

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Article Synopsis
  • - The Cytochrome P450 2D6 (CYP2D6) gene is crucial for metabolizing psychotropic medications, making its testing important for personalized medicine.
  • - A review examines the effectiveness of long-read sequencing (LRS) in improving the sensitivity and accuracy of CYP2D6 phenotyping, showing notable advantages, especially among Oceanians and Japanese individuals with complex genotypes.
  • - Results from six studies indicated that LRS could detect 10% more phenotypes missed by standard tests and correctly identify 4% more mischaracterized phenotypes, highlighting LRS's potential to enhance personalized prescribing of psychotropic drugs.
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Background: Patients with multiple myeloma (MM) are at risk of venous thromboembolism (VTE), worsened by immunomodulatory drugs. Although antithrombotics are recommended for prophylaxis, existing guidelines are suboptimal and treatment outcomes remain unclear.

Objectives: This study aimed to investigate adverse events, antithrombotic utilization, and their associations with survival outcomes in patients with MM initiating multi-drug immunomodulatory combinations.

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Aims: Drug exposure and response is determined by pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Interindividual differences in abundance of drug metabolizing enzymes (DMEs) and drug target proteins underpin PK and PD variability and impact treatment efficacy and tolerability. Extracellular vesicles (EVs) carry protein cargo inherited from originating cells and may be useful for defining differences in key proteins related to hepatic drug metabolism and the treatment of metabolic-associated fatty liver disease (MAFLD).

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Unlocking the full potential of clinical trials through comprehensive CSR and IPD sharing can revolutionize cancer care, enhance safety evaluations, and reduce bias in systematic reviews. It is time for all stakeholders to embrace transparency and advance patient-centered outcomes.

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Background: Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear.

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Objectives: To evaluate the effectiveness of safeguards to prevent large language models (LLMs) from being misused to generate health disinformation, and to evaluate the transparency of artificial intelligence (AI) developers regarding their risk mitigation processes against observed vulnerabilities.

Design: Repeated cross sectional analysis.

Setting: Publicly accessible LLMs.

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Background And Objective: Lung cancer, mainly non-small cell lung cancer (NSCLC), is a serious threat to human life. In particular, the prognosis for advanced patients is poor, with the 5-year survival rate being exceedingly low. In recent years, immune checkpoint inhibition has changed the pattern of the treatment of a variety of cancers, including lung cancer; however, not all patients can benefit from immunotherapy, and thus finding the right biomarkers is particularly important for guiding precise treatment.

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Objectives: Clinical study reports (CSRs) are highly detailed documents that play a pivotal role in medicine approval processes. Though not historically publicly available, in recent years, major entities including the European Medicines Agency (EMA), Health Canada, and the US Food and Drug Administration (FDA) have highlighted the importance of CSR accessibility. The primary objective herein was to determine the proportion of CSRs that support medicine approvals available for public download as well as the proportion eligible for independent researcher request via the study sponsor.

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Proton pump inhibitors (PPIs) are commonly used in cancer patients, but their impact on treatment outcomes in multiple myeloma (MM) patients remains unclear. This study investigated the association of PPI use with survival and adverse effects in MM patients across three randomized-control trials initiating daratumumab, lenalidomide, or bortezomib combination treatments. Cox proportional hazard analysis and logistic regression were employed to assess the associations with treatment outcomes, while adjusting for age, sex, weight, MM international staging system stage, ECOG-performance status, comorbidity count, and presence of gastrointestinal disorders.

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Background: Overall survival (OS) results from randomized control trials (RCT) provide the strongest evidence for efficacy of anti-cancer treatments but can take a considerable amount of time to mature. Progression free survival (PFS) and objective response rate (ORR) are used as an early surrogate of OS treatment effect however their validity remains unclear. Our study aims to comprehensively evaluate ORR and PFS as surrogates for OS treatment effect across tumor groups and treatment types.

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Advances in technologies to isolate extracellular vesicles (EVs) and detect/quantify their cargo underpin the novel potential of these circulating particles as a liquid biopsy to understand physiology and disease. One organ of particular interest in terms of utilizing EVs as a liquid biopsy is the liver. The extent to which EVs originating from the liver reflect the functional status of this organ remains unknown.

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Importance: Although artificial intelligence (AI) offers many promises across modern medicine, it may carry a significant risk for the mass generation of targeted health disinformation. This poses an urgent threat toward public health initiatives and calls for rapid attention by health care professionals, AI developers, and regulators to ensure public safety.

Observations: As an example, using a single publicly available large-language model, within 65 minutes, 102 distinct blog articles were generated that contained more than 17 000 words of disinformation related to vaccines and vaping.

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Data sharing is essential for promoting scientific discoveries and informed decision-making in clinical practice. In 2013, PhRMA/EFPIA recognised the importance of data sharing and supported initiatives to enhance clinical trial data transparency and promote scientific advancements. However, despite these commitments, recent investigations indicate significant scope for improvements in data sharing by the pharmaceutical industry.

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Importance: The pharmaceutical industry has made substantial investments in developing processes for sharing individual-participant data (IPD) from clinical trials. However, the utility and completeness of shared IPD and supporting documents must be evaluated to ensure the potential for scientific advancements from the data sharing ecosystem can be realized.

Objective: To assess the utility and completeness of IPD and supporting documents provided from industry-sponsored clinical trials.

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Article Synopsis
  • Overall survival is the most important measure of treatment success in clinical trials, but it takes time to determine; progression-free survival (PFS) is often used as a quicker indicator, though it has limitations.
  • A study analyzed 138 phase 3 trials published between 2010 and 2022, comparing the effectiveness of PFS, time to quality of life deterioration, and time to physical function deterioration as predictors of overall survival.
  • The results showed that time to deterioration in physical function is particularly useful as a surrogate for overall survival in trials using immune checkpoint inhibitors, especially when combined with PFS, enhancing prediction accuracy.
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Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014.

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Background: Colorectal cancer with synchronous liver-only metastasis is managed with a multimodal approach, however, optimal sequencing of modalities remains unclear.

Methods: A retrospective review of all consecutive rectal or colon cancer cases with synchronous liver-only metastasis was conducted from the South Australian Colorectal Cancer Registry from 2006 to 2021. This study aimed to investigate how order and type of treatment modality affects overall survival.

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Background: Monotherapy immune checkpoint inhibitor (ICI) used in second- or later-line settings has been reported to induce hyperprogression. This study evaluated hyperprogression risk with ICI (atezolizumab) in the first-, second-, or later-line treatment of advanced non-small cell lung cancer (NSCLC), and provides insights into hyperprogression risk with contemporary first-line ICI treatment.

Methods: Hyperprogression was identified using Response Evaluation Criteria in Solid Tumours (RECIST)-based criteria in a dataset of pooled individual-participant level data from BIRCH, FIR, IMpower130, IMpower131, IMpower150, OAK, and POPLAR trials.

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Background: Immune checkpoint inhibitors (ICIs) have been a significant milestone for the treatment of advanced non-small cell lung cancer (NSCLC). However, the efficacy of ICIs can vary substantially between patients, with disparities in treatment outcomes being potentially driving by changes in the microbiome. Antibiotics can cause dysbiosis and are hypothesised to impact the efficacy of ICIs Methods: Data were pooled from five randomised clinical control trials, IMpower130, IMpower131, IMpower150, OAK, and POPLAR, assessing atezolizumab in advanced NSCLC.

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