Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

BACKGROUND: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. PATIENTS AND METHODS: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). RESULTS: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. CONCLUSIONS: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.

Cardiovascular safety of sulphonylureas: over 40 years of continuous controversy without an answer.

More than 40 years after publication of the University Group Diabetes Program trial, the cardiovascular safety of sulphonylureas is still contentious. Although several hypotheses linking sulphonylureas to adverse cardiovascular effects exist, none provide conclusive evidence. Adding to the controversy, current clinical trials and observational studies provide inconsistent, and sometimes conflicting, evidence for the cardiovascular effects of sulphonylureas. Overall, observational evidence suggests that an increased risk of adverse cardiovascular outcomes is associated with sulphonylureas; however, these data may be subject to residual confounding and bias. Although evidence from randomized controlled trials has suggested a neutral effect, the majority of these studies were not specifically designed to assess the effect of sulphonylureas on adverse cardiovascular event risk. Current ongoing large clinical trials may provide some clarity on the cardiovascular safety of sulphonylureas, but the results are not expected for several years. With the continued uncertainties concerning the cardiovascular safety of all antidiabetic drugs, a clear answer with regard to sulphonylureas is warranted. The objectives of the present article were to provide an overview of the controversy surrounding sulphonylurea-related cardiovascular effects, to discuss the limitations of the current literature, and to provide recommendations for future studies aiming to elucidate the true relationship between sulphonylureas and adverse cardiovascular effects in people with type 2 diabetes.

How have pharmacists in different practice settings integrated prescribing privileges into practice in Alberta? A qualitative exploration.

WHAT IS KNOWN AND OBJECTIVE: Since 2007, pharmacists in Alberta have had authority to adapt existing prescriptions and independently prescribe medications after a peer review process. This study aimed to explore and characterize how pharmacists incorporated prescribing into practice 3 years after this legislation was approved. METHODS: We invited pharmacists to participate in semi-structured telephone interviews to discuss their prescribing practices. Pharmacists working in community, primary care network, hospital or other settings were selected using a mix of purposive and random sampling. Two investigators independently analysed each transcript using an Interpretive Description approach and thematically categorized prescribing practices according to the level of adoption. RESULTS AND DISCUSSION: Thirty-eight pharmacists (n = 13 independent prescribers) participated. Eighteen (47%) had a primary practice site from community practice, eight (21%) primary care, five (13%) hospital practice and seven (18%) from other settings including specialty clinics and long-term care. Twenty-eight participants were categorized as adopters and ten as non-adopters in their primary practice setting. Prescribing practices adopted were characterized as product focused, disease focused or patient focused. Sixteen (42%) described product-focused prescribing where they continued an existing therapy or substituted medications based on formulary guidelines. Seven (18%) described disease-focused prescribing where current therapies were adapted or initiated based on a protocol in a specific therapeutic area. Five (13%) described patient-focused prescribing where they initiated therapy based on patient needs and values, their assessment of the patient and best evidence. Non-adopters were not prescribing, but many described provision of disease or patient-focused care where they influenced prescribing by interacting with other members of the healthcare team. Most commonly, community pharmacists participated in product-focused prescribing, whereas hospital and primary care pharmacists practised disease-focused prescribing. WHAT IS NEW AND CONCLUSION: Our data suggest that there have been context-related differences in uptake across practice settings. Despite this, pharmacists in all studied settings engaged in prescribing activities using three approaches and many pharmacists who were not directly prescribing medications reported having involvement in drug therapy decision-making.

Contested claims in carpal tunnel surgery: outcome study of worker's compensation factors.

UNLABELLED: We retrospectively analyzed the importance of factors relating to worker's compensation for 273 wrists in 211 consecutive patients who underwent primary carpal tunnel release. Patients were divided into three groups: non-work related, worker's compensation-uncontested, and worker's compensation-contested. Contested claims were those in which the worker's compensation carrier denied authorization for surgery, and in which such authorization was given following intervention by a plaintiff's attorney. RESULTS: there were no statistically significant differences in postoperative return of grip strength and in postoperative return to work intervals in comparing groups I and II. However, the contested worker's compensation patients were much less likely (and much slower) to return to light duty and to return to full duty work. Return of grip strength was slower and less complete in this group as well. Within worker's compensation, a contested claim portends a poorer prognosis. Uncontested worker's compensation claimants have nearly as good a prognosis as non-compensation patients.

An outbreak of naphthalene di-isocyanate-induced asthma in a plastics factory.

Seven cases of possible naphthalene di-isocyanate-related occupational asthma occurred in 1987 and 1988. These cases were reported to the National Institute for Occupational Safety and Health by personnel at a Midwest factory that manufactured plastic wheels for fork-lift trucks. The reporting of cases prompted (a) an evaluation of the workplace, including a medical screening of workers, to detect additional cases; and (b) an industrial-hygiene survey to determine the level of exposure to isocyanates.

Multipurpose central venous access using the cordis sheath introducer system.

A nonpyrogenic polyethylene sheath system with a hemostatic valve assembly and side port extension developed by the Cordis Corporation is now routinely used for central venous access in critically ill patients. It is inserted percutaneously via the subclavian or internal jugular vein and allows rapid and efficient catheterization for hemodynamic monitoring, infusion of multiple solutions simultaneously, and uniflow hemodialysis. This system represents a significant advance in catheter technology.

Unusual complications during pulmonary artery catheterization.

Two unusual complications, encountered during pulmonary artery catheterization, are described. In both cases the catheter had been introduced percutaneously with the Seldinger technique. Inadvertent entry of the right pleural space occured in one case in which the catheter had been inserted into the internal jugular vein through a low cervical approach. The second complication was separation of the shaft of the introducer from the hub, with consequent risk of embolization. Possible means of preventing and treating these complications are discussed.