Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

Top Management Involvement in New Product Development: A Review and Synthesis

Established literature on new product development (NPD) management recognizes top management involvement (TMI) as one of the most critical success factors. With increasing pressure to sustain competitive advantage and growth, NPD activities remain the focus of close interest from top management in many organizations. TMI in the NPD domain is receiving increasing academic attention. Despite its criticality, there is no systematic review of the existing literature to inform and stimulate researchers in the field for further investigation. This paper introduces the current state of literature on TMI in NPD, synthesizes important findings, and identifies the gaps and deficiencies in this research stream. The contents of the selected articles, which investigated TMI in NPD, are analyzed based on the type of the study, level of analysis, research methodology, operationalization of TMI, and main findings. Additionally, other studies, which did not directly investigate TMI and support in NPD, but were sufficiently related, are briefly summarized. As a result of this detailed literature review, it can be stated that both exploratory and relational studies provide rich evidence on the critical role of top management in NPD. However, the identified gaps and deficiencies in this research stream call for a better theoretical understanding and well-defined constructs of TMI in the NPD domain for different levels of analysis for future studies.