Effect of obesity on recombinant follicle-stimulating hormone absorption: subcutaneous versus intramuscular administration

OBJECTIVE: To determine whether recombinant follicle-stimulating hormone (rFSH) should be administered intramuscularly (i.m.) or subcutaneously (s.c.) to obese women. DESIGN: Randomized, single-center, two-way crossover study. SETTING: Academic clinical research center. SUBJECT(S): Nineteen healthy women of reproductive age with body mass indices of 19.9 kg/m(2)-42.8 kg/m(2). INTERVENTION(S): Leuprolide acetate 3.75 mg i.m. to achieve pituitary down-regulation as determined by serum E(2) levels. Subjects were then given a single dose of 300 IU rFSH either i.m. or s.c.. Multiple blood sampling was performed over the next two weeks, and after retreatment with leuprolide, a second 300 IU rFSH dose was given via the other administration route. MAIN OUTCOME MEASURE(S): Serum samples were analyzed in duplicate for follicle-stimulating hormone (FSH) using a standard radioimmunoassay in a single run. Maximum concentrations (C(max)), times to C(max) (T(max)), and extent of absorption (area under curve [AUC]) with i.m. vs. s.c. administration were compared using paired analysis. RESULT(S): Maximal concentrations were achieved within 24 hours with both s.c. and i.m. routes. No significant differences were found in C(max), T(max), or AUC with s.c. vs. i.m. administration. A decline of AUC occurred among subjects of higher body mass index (BMI) with rFSH given either s.c. or i.m.. Subcutaneous administration achieved AUCs comparable to i.m. administration in both normal-weight and obese subjects. CONCLUSION(S): Our data indicate that the s.c. administration of rFSH is appropriate for women regardless of body mass.     

Making the boundaries clearer: revisiting information systems with fading boundaries

PURPOSE: To address issues of importance in 1994 and what has happened in those issues. METHODS: A number of questions and issues will be examined. Were we right in our focus at that time and what did we miss? What has happened that perhaps changed our perspectives and philosophies? Has the need changed? Is the model of fading boundaries a correct one, and how far have we gone in realizing a communication system in dealing with those boundaries? What progress have we made internationally on these issues? How are we working internationally to solve these problems? RESULTS: The fifth working conference relating to hospital information systems (HIS) was held in Durham, North Carolina in August 1994. The Institute of Medicine publication The Computer-based Patient Record: An Essential Technology for Health Care had been published in 1991 and had begun influencing thinking and direction for clinical information systems. The difference between and relationship of HIS and Computer-based Patients Records was the topic of much discussion and debate. The 1994 conference strongly recognized the need for standards specifically for data exchange, unique patient identifier, data definitions and common clinical data sets and for clinical terminology. Interconnectivity and interoperability were identified as separate but related problems to be solved. Technology was not considered to be a barrier, and projections for bandwidth to meet data dissemination requirements were favorable. In the 7 years after the Durham conference, many things have changed dramatically. Progress has been made in a number of areas, and some of the projections have been realized. However, it is surprising to note what areas still remain problems, particularly noting what problems have been worked on without success and what problems have not even been addressed. It is interesting to speculate that if the Durham conference was repeated today, would it be accepted as a current event?     

Collaborative drug therapy management by pharmacists--2003

Since publication of the initial ACCP position statement on CDTM by pharmacists in 1997, the public, government, and much of the health care community at large have come to better appreciate the growing complexity of providing effective and safe drug therapy in today's health care environment. Increased interest in the issues of cost and quality of drug use is evident in the increasing coverage of the issue in the lay press and professional literature. This represents real progress, as well as real opportunity, for pharmacists. It also heightens the potential for a better understanding of the vital role that pharmacists can play in addressing these concerns. The percentage of patients who take several drugs for chronic diseases will continue to increase. Based on current trends, the number of patients who lack adequate access to care, or who receive either suboptimal, inappropriate, or unnecessarily expensive drug therapy for their acute and chronic diseases, will increase. Even as financial and human resources are increasingly strained within the current health care system, costs will continue to rise unless changes are made. Fortunately, qualified pharmacists are prepared, capable, and willing to help address a significant portion of these challenges. The public, many health care providers, some legislators, and a few insurers now recognize that pharmacists, because of their education and training in drug therapy, are well positioned both to accept additional responsibility for patient care and to provide services that make a real difference in health care quality and outcomes. The health care programs administered by the U.S. Public Health Service, the armed forces, and the Veterans Health Administration, as well as 38 states, now support pharmacist participation in CDTM. Pharmacists, working in an interdisciplinary structure with physicians and other health care providers, have demonstrated that they can improve the effectiveness, efficiency, and safety of drug therapy by providing CDTM. It is time to incorporate this valuable professional skill of the contemporary pharmacist as a core component of the delivery of health care services.     

Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo

Insulin resistance plays a central role in the development of type 2 diabetes, but the precise defects in insulin action remain to be elucidated. Glycogen synthase kinase 3 (GSK-3) can negatively regulate several aspects of insulin signaling, and elevated levels of GSK-3 have been reported in skeletal muscle from diabetic rodents and humans. A limited amount of information is available regarding the utility of highly selective inhibitors of GSK-3 for the modification of insulin action under conditions of insulin resistance. In the present investigation, we describe novel substituted aminopyrimidine derivatives that inhibit human GSK-3 potently (K(i) < 10 nmol/l) with at least 500-fold selectivity against 20 other protein kinases. These low molecular weight compounds activated glycogen synthase at approximately 100 nmol/l in cultured CHO cells transfected with the insulin receptor and in primary hepatocytes isolated from Sprague-Dawley rats, and at 500 nmol/l in isolated type 1 skeletal muscle of both lean Zucker and ZDF rats. It is interesting that these GSK-3 inhibitors enhanced insulin-stimulated glucose transport in type 1 skeletal muscle from the insulin-resistant ZDF rats but not from insulin-sensitive lean Zucker rats. Single oral or subcutaneous doses of the inhibitors (30-48 mg/kg) rapidly lowered blood glucose levels and improved glucose disposal after oral or intravenous glucose challenges in ZDF rats and db/db mice, without causing hypoglycemia or markedly elevating insulin. Collectively, our results suggest that these selective GSK-3 inhibitors may be useful as acute-acting therapeutics for the treatment of the insulin resistance of type 2 diabetes.     

Surgeon experience and clinical and economic outcomes for shoulder arthroplasty

BACKGROUND: Previous studies have demonstrated that a high surgical volume for certain surgical procedures reduces morbidity and improves economic outcome; however, to our knowledge, no study has demonstrated a similar relationship between volume and outcome for total shoulder arthroplasty and hemiarthroplasty. The objective of this study was to determine whether increased surgeon experience was associated with improved clinical and economic outcomes for patients undergoing total shoulder arthroplasty or hemiarthroplasty. METHODS: We analyzed discharge data on patients treated between 1994 and 2000 from the Maryland Health Services Cost Review Commission, which has a statewide hospital discharge database of all patients in the state of Maryland. The database included all patients undergoing total shoulder arthroplasty and hemiarthroplasty. We assessed the relationship between surgeon volume (low, medium, and high) and the risk of complications, length of stay, and total charges. The statistics were adjusted for procedure, age, gender, race, marital status, comorbidity, diagnosis, insurance type, income, and hospital volume. RESULTS: For the 1868 discrete total shoulder arthroplasties and hemiarthroplasties done in the state of Maryland, the risk of at least one complication associated with the procedures done by the high-volume surgeon group was nearly half that associated with the procedures done by the low-volume surgeon group (adjusted odds ratio, 0.6; 95% confidence interval, 0.4 to 0.9). High-volume surgeons were three times more likely than were low-volume surgeons to have patients with a hospital stay of less than six days (odds ratio, 0.3; 95% confidence interval, 0.2 to 0.6). Although the average cost of hospitalization was $1000 less in the high-volume surgeon group compared with the low-volume surgeon group, this reduction did not reach significance after adjustment for multiple variables (odds ratio, 0.8; 95% confidence interval, 0.5 to 1.4). CONCLUSIONS: This study indicates that the patients of surgeons with higher average annual caseloads of total shoulder arthroplasties and hemiarthroplasties have decreased complication rates and hospital lengths of stay compared with the patients of surgeons who perform fewer of these procedures. These analyses of hospital discharge data are limited because of a lack of prospective data, operative details, and patient outcomes data. However, this study emphasizes the importance of continued education for orthopaedic surgeons who perform shoulder arthroplasty.     

Attitudes about prescribing take-home naloxone to injection drug users for the management of heroin overdose: a survey of street-recruited injectors in the San Francisco Bay Area

Naloxone, an injectable opiate antagonist, can immediately reverse an opiate overdose and prevent overdose death. We sought to determine injection drug users’ (IDUs) attitudes about being prescribed take-home naloxone. During November 1999 to February 2000, we surveyed 82 street-recruited IDUs from the San Francisco Bay Area of California who had experienced one or more heroin overdose events. We used a questiomaire that included structured and open-ended questions. Most respondents (89%) had witnessed an overdose, and 90% reported initially attempting lay remedies in an effort to help companions survive. Only 51% reported soliciting emergency assistance (calling 911) for the last witnessed overdose, with most hesitating due to fear of police involvement. Of IDUs surveyed, 87% were strongly in favor of participating in an overdose management training program to receive take-home naloxone and training in resuscitation techniques. Nevertheless, respontdents expressed a variety of concerning attitudes. If provided naloxone, 35% predicted that they might feel comfortable using greater amounts of heroin, 62% might be less inclined to call 911 for an overdose, 30% might leave an overdose victim after naloxone resuscitation, and 46% might not be able to dissuade the victim from using heroin again to alleviate with drawal symptoms induced by naloxone. Prescribing take-home naloxone to IDUs with training in its use and in resuscitation techniques may represent a life-saving, peer-based adjunct to accessing emergency services. Nevertheless, strategies for overcoming potential risks associated with the use of take-home naloxone would need to be emphasized in an overdose management training program.     

A one-year experience with a capitated health care plan for infertility

OBJECTIVE: To report on a one-year experience participating in a capitated healthcare plan for infertility. DESIGN: Prospective study. SETTING: University population. PATIENT(S): Reproductive-age women 15 to 50 years. INTERVENTION(S): The first-generation Lewin infertility algorithm and CATHI software were used to negotiate infertility services under a capitated arrangement for $0.50 per member per month. The following reports our experience for the fiscal year 1997. MAIN OUTCOME MEASURE(S): Infertility services rendered, pregnancy rate, cost of services, collection rates. RESULT(S): Five thousand forty-six women representing 39,689 member months generated 39 new and 198 return visits. Thirty-two percent of the patients required three visits or less; six patients generated 22% of the visits. Fifty-one percent listed infertility as one of their chief complaints; 31% had mixed diagnoses. Eight (7.6%) patients required surgery, 11 (10.5%) patients underwent either IVF or GIFT cycles. Total charges submitted were $176,636; the amount assigned to specialty care was $135,277, and to IVF/GIFT, $33,433. Total capitated payments, including copayments, was $126,256 under the reproductive medicine agreement and $32,891 under the infertility rider. This resulted in a 71% gross collections rate. CONCLUSION(S): This study indicates that entering into a capitated health care plan to provide an infertility benefit can produce a successful result.