Dietary supplement beliefs and use patterns among Irish patients with early-stage breast cancer.

BACKROUND: Level one evidence reported poorer outcomes among patients taking dietary supplements after breast cancer (BC) diagnosis. METHODS: We evaluated dietary supplement behaviours among adult BC patients via questionnaire. Sociodemographic data, supplement use, attitudes, and healthcare provider (HCP) advice were analysed. RESULTS: Of 185 participants, 45% were regular supplement users following diagnosis. Regular supplement use was associated with higher education level (p = 0.05). The majority perceived supplements to be safe. Over half reported not receiving advice from HCPs. CONCLUSION: In summary, supplement use is prevalent among BC patients. Development of guidelines in relation to safe use of dietary supplements after cancer diagnosis is crucial.

The coexistence of autoimmune diabetes and maturity-onset diabetes of the young (MODY): a case series.

Summary: The coexistence of autoimmune diabetes and maturity-onset diabetes (MODY) is rare. The absence of pancreatic autoantibodies is a key factor prompting MODY genetic testing. In this study, we report three cases of young-onset diabetes with progressive beta-cell dysfunction, strongly positive glutamic acid decarboxylase (GAD) antibodies, and genetic confirmation of pathogenic gene variants of HNF-1A, HNF-4A, and ABCC8-MODY. The first case is a woman diagnosed with HNF-1A-MODY diabetes more than 30 years after her diagnosis of adult-onset diabetes at 25 years. She required insulin after her fourth pregnancy. She became ketotic on oral hypoglycaemic agents (OHAs) and subsequently, her GAD antibodies tested positive. The second case is a woman diagnosed with diabetes at 17 years who was subsequently diagnosed with HNF-4A-MODY after many hypoglycaemic episodes on low-dose insulin. GAD antibodies were strongly positive. The last case is a man diagnosed with diabetes at 26 years who was well controlled on OHAs and required insulin years later due to sudden deterioration in glycaemic control. His ABCC8-MODY was diagnosed upon realisation of strong family history and his GAD antibodies tested positive. All subjects are now treated with insulin. Less than 1% of subjects with MODY have positive autoantibodies. These cases highlight individuals who may have two different types of diabetes simultaneously or consecutively. Deterioration of glycaemic control in subjects with MODY diabetes should highlight the need to look for the emergence of autoantibodies. At each clinic visit, one should update the family history as MODY was diagnosed in each case after the development of diabetes in their offspring. Learning points: These cases highlight the rare coexistence of autoimmune diabetes and MODY. Deterioration of glycaemic control in subjects with MODY diabetes should highlight the emergence of autoantibodies. One should revise and update the family history as the diagnosis of MODY was made after the development of diabetes in offspring. Understanding the spectrum of diabetes allows for precision medicine.

Application of quality by design principles to the development and technology transfer of a major process improvement for the manufacture of a recombinant protein.

This study describes the application of quality by design (QbD) principles to the development and implementation of a major manufacturing process improvement for a commercially distributed therapeutic protein produced in Chinese hamster ovary cell culture. The intent of this article is to focus on QbD concepts, and provide guidance and understanding on how the various components combine together to deliver a robust process in keeping with the principles of QbD. A fed-batch production culture and a virus inactivation step are described as representative examples of upstream and downstream unit operations that were characterized. A systematic approach incorporating QbD principles was applied to both unit operations, involving risk assessment of potential process failure points, small-scale model qualification, design and execution of experiments, definition of operating parameter ranges and process validation acceptance criteria followed by manufacturing-scale implementation and process validation. Statistical experimental designs were applied to the execution of process characterization studies evaluating the impact of operating parameters on product quality attributes and process performance parameters. Data from process characterization experiments were used to define the proven acceptable range and classification of operating parameters for each unit operation. Analysis of variance and Monte Carlo simulation methods were used to assess the appropriateness of process design spaces. Successful implementation and validation of the process in the manufacturing facility and the subsequent manufacture of hundreds of batches of this therapeutic protein verifies the approaches taken as a suitable model for the development, scale-up and operation of any biopharmaceutical manufacturing process.