Pramlintide in the Management of Insulin-Using Patients with Type 2 and Type 1 Diabetes

In patients with diabetes, dysregulation of multiple glucoregulatory hormones results in chronic hyperglycemia and an array of associated microvascular and macrovascular complications. Optimization of glycemic control, both overall (glycosylated hemoglobin [A1C]) and in the postprandial period, may reduce the risk of long-term vascular complications. However, despite significant recent therapeutic advances, most patients with diabetes are unable to attain and/or maintain normal or near-normal glycemia with insulin therapy alone. Pramlintide, an analog of amylin, is the first in a new class of pharmaceutical agents and is indicated as an adjunct to mealtime insulin for the treatment of patients with type 1 and type 2 diabetes. By mimicking the actions of the naturally occurring hormone amylin, pramlintide complements insulin by regulating the appearance of glucose into the circulation after meals via three primary mechanisms of action: slowing gastric emptying, suppressing inappropriate post-meal glucagon secretion, and increasing satiety. In long-term clinical trials, adjunctive pramlintide treatment resulted in improved postprandial glucose control and significantly reduced A1C and body weight compared with insulin alone. The combination of insulin and pramlintide may provide a more physiologically balanced approach to managing diabetes

A Market Utility-Based Model for Capacity Scheduling in Mass Services

Only a small set of employee scheduling articles have considered an objective of profit or contribution maximization, as opposed to the traditional objective of cost (including opportunity costs) minimization. In this article, we present one such formulation that is a market utility-based model for planning and scheduling in mass services (mums), mums is a holistic approach to market-based service capacity scheduling. The mums framework provides the structure for modeling the consequences of aligning competitive priorities and service attributes with an element of the firm’s service infrastructure. We developed a new linear programming formulation for the shifts-scheduling problem that uses market share information generated by customer preferences for service attributes. The shift-scheduling formulation within the framework of mums provides a business-level model that predicts the economic impact of the employee schedule. We illustrated the shift-scheduling model with empirical data, and then compared its results with models using service standard and productivity standard approaches. The result of the empirical analysis provides further justification for the development of the market-based approach. Last, we discuss implications of this methodology for future research

Service Capacity Design With an Integrated Market Utility-Based Method

[Excerpt] The purpose of this chapter is to present a model that integrates customer preferences and service design. In response to the need for interdisciplinary service management research, we present a framework that specifies the key elements of an integrated market utility-based model (MUM) and a method for determining optimal service designs based on customer needs and preferences. We also explore the relationships among revenue, capacity costs, and those service design attributes that have significant operational consequences. Our model builds on the topics we have described and integrates customer utility models that are commonly used in market research with capacity variables and their corresponding costs that are typical operations management issues. The proposed method is general and can be adapted for different types of service operations

Designing and Positioning Food Services for Multicultural Markets

[Excerpt] Businesses that seek to develop an appropriate operations strategy for serving a multicultural customer market face challenges that are distinct from businesses that serve a relatively homogeneous local market. While the strategic implications of expanding services from a domestic market to international locations have been well documented, the issue of dealing with multinational customers at a single location has largely been neglected by researchers, as far as we can determine. This paper attempts to fill the research gap by presenting a method for determining the extent to which restaurant managers should maintain standard menus and food items, as opposed to customizing their operations for different ethnic and cultural groups. To that end, we applied a customer-based approach to help managers at four international-airport food outlets to improve their food- service revenues from their three major passenger groups: English-, Japanese-, and Spanish-speaking customers. In this case, language preference was used as a proxy for cultural identity. We submit that although there are many differences among, say, English-speaking peoples, they are more similar to each other than they are to, say, Spanish speakers. Moreover, the language a person speaks is a substantial factor in trying to communicate in a particular location. One can guess that Japanese speakers in the United States, for example, might experience more language barriers than either English or Spanish speakers. We present an approach for modeling the preferences of different cultural groups, evaluating the differences among the groups, and determining a strategy to maximize market share for each of the four food-service providers that we studied. Indeed, one food-service vendor implemented our study\u27s recommendations and enjoyed a substantial revenue gain over the previous year\u27s same-period sales. We believe that the method we propose has valuable implications for any service provider who must consider operating strategies for a multicultural or multinational site, although we focus on the distinct concept of a domestic foodservice business that serves a multicultural market

A Market-Utility Approach to Scheduling Employees

[Excerpt] Scheduling front-line service providers is a constant challenge for hospitality managers, given the inevitable tradeoff between service standards and operating expense. Traditional employee scheduling typically applies a cost-minimization approach to specify the level of front-line service providers who will be available to meet periodic demand. That cost includes the opportunity cost of lost customers, which is part of the pseudo-costs of understaffing. A confounding and often ignored effect, however, is the benefit generated by maintaining high service levels in a system where capacity exceeds demand. That is, scheduling more frontline service providers than the minimum level necessary to provide acceptable customer service (what might be considered to be overstaffing in some rubrics) may mean that customers receive service that is better than they expected (or what company standards prescribe). In this paper we report on a scheduling approach that explicitly considers the interrelationships among customer preferences, customer demand, waiting times, and scheduling decisions. This approach, which we call the market-utility model for scheduling (MUMS), helps managers consider the dynamics of scheduling service employees. First, we discuss the components that make up this approach, which includes methods from customer-preferences modeling, service-capacity planning, and the four tasks of labor scheduling proposed by Thompson. Next, we\u27ll show how the model applies to balancing queue lengths and operating costs for an airport food-court vendor. Finally, we discuss the value of MUMS for hospitality managers

A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study.

Abstract Background Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia. Methods Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days. Results In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%). Conclusions This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647)

Nonmotor Symptoms in LRRK2 G2019S Associated Parkinson's Disease

BACKGROUND: Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined. OBJECTIVE: To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients. METHODS: The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated. RESULTS: University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination. CONCLUSION: Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD

Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.

OBJECTIVE: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. METHODS: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers. RESULTS: A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E-07; age-at-onset top variant: p value = 9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset. INTERPRETATION: This study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82-94