Mealtime fast-acting insulin aspart versus insulin aspart for controlling postprandial hyperglycaemia in people with insulin-resistant Type 2 diabetes.

AIM: This post hoc analysis explored whether mealtime fast-acting insulin aspart treatment provided an advantage in postprandial plasma glucose (PPG) control vs. insulin aspart in people with Type 2 diabetes receiving high doses of bolus insulin. METHODS: A post hoc, post-randomization, subgroup analysis of a 26-week, randomized, double-blind, treat-to-target trial (onset 2) that compared mealtime fast-acting insulin aspart vs. mealtime insulin aspart, both in a basal-bolus regimen, in people with Type 2 diabetes uncontrolled on basal insulin therapy and metformin. At the end of trial, the impact of fast-acting insulin aspart and insulin aspart on PPG control was assessed with a standard liquid meal test and participants were grouped into three post-randomization subgroups: meal test bolus insulin dose ≤ 10 units per dose (n = 171), > 10-20 units per dose (n = 289) and > 20 units per dose (n = 146). RESULTS: A statistically significant treatment difference in favour of fast-acting insulin aspart vs. insulin aspart was observed for the change in PPG increment at all post-meal time points (from 1 to 4 h) for those in the > 20 units bolus insulin subgroup. There was no difference in the magnitude of change from baseline in HbA1c level between fast-acting insulin aspart and insulin aspart in any of the bolus insulin dose subgroups (data herein). CONCLUSION: Fast-acting insulin aspart may hold promise as a more effective treatment compared with insulin aspart for controlling PPG in people with insulin-resistant Type 2 diabetes.

Direct comparison of the BD phoenix system with the MicroScan WalkAway system for identification and antimicrobial susceptibility testing of Enterobacteriaceae and nonfermentative gram-negative organisms.

The Phoenix automated microbiology system (BD Diagnostics, Sparks, MD) is designed for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically significant human bacterial pathogens. We evaluated the performance of the Phoenix instrument in comparison with that of the MicroScan WalkAway system (Dade Behring, West Sacramento, CA) in the ID and AST of gram-negative clinical strains and challenge isolates of Enterobacteriaceae (n = 150) and nonfermentative gram-negative bacilli (NFGNB; 45 clinical isolates and 8 challenge isolates). ID discrepancies were resolved with the API 20E and API 20NE conventional biochemical ID systems (bioMerieux, Durham, NC). The standard disk diffusion method was used to resolve discordant AST results. The overall percentages of agreement between the Phoenix ID results and the MicroScan results at the genus and species levels for clinical isolates of Enterobacteriaceae were 98.7 and 97.7%, respectively; following resolution with conventional biochemical testing, the accuracy of the Phoenix system was determined to be 100%. For NFGNB, the levels of agreement were 100 and 97.7%, respectively. Both systems incorrectly identified the majority of the uncommon nonfermentative nonpseudomonal challenge isolates recovered from cystic fibrosis patients; these isolates are not included in the databases of the respective systems. For AST of Enterobacteriaceae, the rate of complete agreement between the Phoenix results and the MicroScan results was 97%; the rates of very major, major, and minor errors were 0.3, 0.2, and 2.7%, respectively. For NFGNB, the rate of complete agreement between the Phoenix results and the MicroScan results was 89.1%; the rates of very major, major, and minor errors were 0, 0.5, and 7.7%, respectively. Following the confirmatory testing of nine clinical isolates initially screened by the MicroScan system as possible extended-spectrum-beta-lactamase (ESBL)-producing organisms (seven Klebsiella pneumoniae isolates and two Escherichia coli isolates), complete agreement was achieved for eight isolates (one ESBL positive and seven negative); one false positive was obtained with the Phoenix instrument. The MicroScan system correctly detected the 10 ESBL challenge isolates, versus the 6 detected by the Phoenix system. Overall, there was good correlation between the Phoenix instrument and the MicroScan system for the ID and AST of Enterobacteriaceae and common NFGNB. The Phoenix system is a reliable method for the ID and AST of the majority of clinical strains encountered in the clinical microbiology laboratory. Until additional performance data are available, results for all Klebsiella pneumoniae or Klebsiella oxytoca and E. coli isolates screened and confirmed as ESBL producers by any automated system should be confirmed by alternate methods prior to the release of final results.

Linking pharmacy and laboratory data to assess the appropriateness of care in patients with diabetes.

OBJECTIVE: To use pharmacy and laboratory data to assess diabetes care within a medical group and between medical groups and to determine dispensing patterns and the extent to which providers change therapy based on HbA1c results. RESEARCH DESIGN AND METHODS: Participating groups submitted 1 year of data for continuously enrolled patients. Required data included date of birth, all diabetes-specific prescriptions (oral hypoglycemic agents and insulin), date of prescription, National Drug Code, all HbA1c values, lower and upper normal limits, and date of testing. RESULTS: Few changes in therapy were noted despite the large percentages of patients with suboptimal control. Nearly 90% of the patients treated with medications received a monotherapy regimen involving one of three therapeutic agents: sulfonylureas, metformin, or insulin. More than three-fourths of the patients remained on the same therapy during the observation period despite the fact that 27% of these patients had HbA1c values > or = 8%. Nearly one-fifth (18%) of patients had an HbA1c level of > or = 8% and no further testing for at least 90 days after the "actionable" HbA1C result was obtained. Furthermore, 54% of patients with actionable HbA1c results did not have a change in therapy initiated after the result was available. CONCLUSIONS: The American Diabetes Association recommendations to act on HbA1c values > or = 8% and to follow up regularly on patients found to be in suboptimal control do not appear to be applied in a consistent manner based on the pharmacy and laboratory data analyzed in this sample.

A systematic approach to risk stratification and intervention within a managed care environment improves diabetes outcomes and patient satisfaction.

OBJECTIVE: To determine whether a comprehensive diabetes management program that included risk stratification and social marketing would improve clinical outcomes and patient satisfaction within a managed care organization (MCO). RESEARCH DESIGN AND METHODS: The 12-month prospective trial was conducted at primary care clinics within a MCO and involved 370 adults with diabetes. Measurements included 1) the frequency of dilated eye and foot examinations, microalbuminuria assessment, blood pressure measurement, lipid profile, and HbA(1c) measurement; 2) changes in blood pressure, lipid levels, and HbA(1c) levels; and 3) changes in patient satisfaction. RESULTS: Complete data are reported for the 193 patients who had been enrolled for 12 months; life table analysis is reported for all patients who remained enrolled at the study's end as well as for a comparative control group of 623 patients. For the 193 patients for whom 12-month data were available, the number of patients in the low-risk category (HbA(1c) <7%) increased by 51.1%. A total of 97.4% of patients with an HbA(1c) >8% at baseline had a change in treatment regimen. Patients at the highest risk for coronary heart disease (LDL >130 mg/dl) decreased from 25.4% at baseline to 20.2%. Patients with a blood pressure <130/85 mmHg increased from 23.8 to 44.6%. Of these patients, 63.0% had changes in medication. Patients and providers expressed significant increases in satisfaction with the program. CONCLUSIONS: The program was successful in initiating the recommended changes in the diabetic therapeutic regimen, resulting in improved glycemic control, increased monitoring/management of diabetic complications, and greater patient and provider satisfaction. These results should have great significance in the design of future programs in MCOs aimed at improving the care of people with diabetes and other chronic diseases.

Vancomycin-resistant enterococcus in end-stage renal disease.

The percentage of nosocomial vancomycin-resistant enterococci (VRE) has been increasing rapidly in the United States. This has recently resulted in recommendations to reserve vancomycin use for cases with proven resistance to other antimicrobials. We prospectively investigated the incidence of VRE in our dialysis population and compared it with a control group of 40 clinic patients with chronic renal insufficiency (CRI) who had a serum creatinine level greater than 1.5 mg/dL, but were not undergoing dialysis. The incidence of VRE on our campus is almost 10%, which is similar to US data. We studied 50 chronic hemodialysis (HD) patients and 50 peritoneal dialysis (PD) patients. Each patient had a rectal swab test performed and cultured for the presence of enterococci. Antimicrobial exposures over the 6 months before the initial swab test were reviewed in each patient. At least one repeated swab test was performed in 30 CRI, 45 HD, and 37 PD patients. From the initial swab culture, vancomycin-sensitive enterococci (VSE) were isolated in 65% of CRI, 54% of HD, and 70% of PD patients. No CRI or HD patients had VRE isolated and 2% (1 of 50) of PD patients had VRE isolated. The remaining patients had no enterococci isolated. Review of antimicrobial exposures in the 6 months before the initial swab test showed 0% of CRI, 32% of HD, and 36% of PD patients received vancomycin. Other antimicrobials were administered to 40% of CRI, 46% of HD, and 78% of PD patients in the same time period. In the month immediately preceding the initial swab test, 0% of CRI, 12% of HD, and 22% of PD patients received vancomycin and 18% of CRI, 20% of HD, and 36% of PD patients received other antimicrobials. Results from repeated cultures showed that 57% of CRI, 40% of HD, and 38% of PD patients changed their culture status related to VSE, VRE, or no enterococci present. Cultures of 342 swabs from 140 patients yielded three VRE isolates in two patients. We conclude that despite the frequent use of vancomycin and other antimicrobials, the incidence of VRE in our renal population is less than the reported incidence. Given this lack of VRE isolates, we recommend the continued judicious use of vancomycin in treating renal patients and continued enterococcal sensitivity surveillance.

Protection by cyclosporin A of cultured hepatocytes from the toxic consequences of the loss of mitochondrial energization produced by 1-methyl-4-phenylpyridinium.

Cyclosporin A prevented the killing of cultured rat hepatocytes by 1-methyl-4-phenylpyridinium (MPP+). However, in the presence of both cyclosporin and atractyloside, there was no protection. Cyclosporin had no effect on the depletion of ATP or the loss of mitochondrial energization by MPP+. Cyclosporin, however, did prevent the increase in the molecular order of hepatocyte membranes produced by MPP+. These data suggest that mitochondrial de-energization produced by MPP+ is accompanied by a "permeability transition" analogous to that which occurs in vitro in the presence of calcium. By preventing this transition, cyclosporin protects the cells. By antagonizing this action of cyclosporin, atractyloside restores the cell killing. The mitochondrial transition is causally linked to cell killing by a mechanism that increases the molecular order of the hepatocyte plasma membrane.

Antibacterial effect of cyanoacrylate glue.

Enbucrilate (butyl-2-cyanoacrylate; Histoacryl [West Germany], no comparable US product) is a tissue adhesive used in the management of corneal perforations that may have a therapeutic value in suppressing selective pathogens isolated, from corneal infections. In three patients with confirmed corneal infections, varying degrees of inhibition were observed. Bacteriostatic activity was most pronounced against gram-positive microorganisms, and no activity was observed against gram-negative organisms. It appears that this chemical adhesive provided an ancillary means of promoting healing of corneal perforations.

A combined molecular approach to screen for mec gene variants from methicillin-resistant Staphylococcus aureus.

Previous reports have suggested a common origin for all methicillin resistance (mec) genes from methicillin-resistant Staphylococcus aureus (MRSA) isolates examined so far. The purpose of this study was to explore several molecular methods for screening MRSA isolates from different sources and, in some cases, with varying phenotypes. Eighty MRSA isolates from three teaching hospitals in the University of Louisville Medical Center were compared with MRSAs from a hospital in southern California and with methicillin-sensitive S. aureus isolates. The methods were used to detect the presence of mec gene and to screen for any polymorphisms in these genes for the respective strains. The mec gene for each isolate was amplified via the polymerase chain reaction, and each polymerase chain reaction product was compared to the others by restriction enzyme digestion, denaturing-gradient gel electrophoresis, and mutation detection enhancement. By these criteria, the mec genes from the 80 MRSA strains in this study seemed to be identical. Such a finding was not unexpected and supported the existing hypothesis of a common ancestor for all mec genes isolated in MRSA isolates. However, the combination of methods used in this study may facilitate screening of MRSA strains in population studies as mec gene variants begin to emerge.

An in vitro study of the potency and stability of fortified ophthalmic antibiotic preparations.

We studied the potency of fortified ophthalmic antibiotic preparations of cefazolin sodium (50 mg/ml) and tobramycin sulfate (15 mg/ml), as measured by the minimum inhibitory concentration, against Streptococcus pneumoniae and Pseudomonas aeruginosa, respectively. We also examined absorbance spectra, pH, and the effect of storage temperature on these fortified solutions to determine their stability over a four-week period. Cefazolin and tobramycin maintained a constant potency throughout the experiment. There was no difference in potency if the fortified solutions were stored at 4 C or 24 C. Cefazolin stored at 24 C exhibited changes in both its absorbance spectra and pH after seven days. Cefazolin stored at 4 C and tobramycin stored at 24 C and 4 C remained stable throughout the four-week period.

Serratia keratitis transmitted by contaminated eyedroppers.

Serratia marcescens keratitis developed in three patients after keratoplasty. Two patients were using prednisolone sodium phosphate eyedrops and the third was using 0.5% timolol maleate eyedrops. All three cases resolved after treatment with topically and subconjunctivally administered antibiotics. Although S. marcescens was isolated from the outer grooves of the bottletops and from the inner surfaces of the eyedropper caps, it was not cultured from the solutions in the bottles. Moisture collecting in the dead space between the cap and bottle was apparently a culture medium for Serratia. When eyedrops were expressed into the patient's eyes, the eyes were inoculated with Serratia from the contaminated liquid flowing down the eyedropper shaft.

Changes in the American health care system: crisis in the clinical laboratory.

American medicine is undergoing unprecedented changes, and the resulting distortions are affecting the economics, organization and operations of all clinical laboratories. Professionals who work in these laboratories are facing administrative and economic pressures to reduce costs, to increase productivity, and to comply with proliferating new statutes and regulations. The medical 'cottage industry' in which the patient was the focus of the medical professionals' attention and endeavours is being replaced by the corporate management of many health care activities in which financial profits are being given first priority. Medical facilities, including clinical laboratories, are being bought and sold, being consolidated, or simply being closed. The clinical laboratories may be at the vortex of the maelstrom affecting American medicine. Cost pressures are encouraging further automation and retraining of laboratory staffs. If the leaders in laboratory medicine are unable to accomplish the necessary tasks to meet the new challenges, there inevitably is a non-medical, non-scientific financial manager at hand who is willing to define the changes and the desired outcome. Because of the rapidity of the changes taking place, it is not possible to predict with any confidence the modifications that will achieve a permanent status or the degree to which medical professionals will remain masters of their fates. The evolving health care system will become less costly, more technologically advanced, and a more challenging system in which to work.

Mechanisms of toxic cell injury.

The biochemical mechanisms by which xenobiotic agents initiate cell injury involve networks of interactions at a variety of molecular and structural targets. The author highlights current concepts in six major areas of investigation: covalent binding, oxidative stress, alterations of glutathione and protein thiols, peroxidation and hydrolysis of phospholipids, mitochondrial deenergization, and alterations of intracellular calcium homeostasis.

N-methyl-4-phenylpyridinium (MPP+) potentiates the killing of cultured hepatocytes by catecholamines.

The role of catecholamines in the toxicity of MPTP (N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine) was explored. The killing of cultured hepatocytes by dopamine and 6-hydroxydopamine was enhanced following inhibition of glutathione reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a manipulation known to sensitize such cells to an oxidative stress. The participation of activated oxygen species in the cell injury under such circumstances was shown by the ability of catalase and the ferric iron chelator deferoxamine to protect the hepatocytes. The toxicity of catecholamines was also potentiated by the mitochondrial site I (NADH dehydrogenase) inhibitor rotenone. MPP+ (N-methyl-4-phenyl-pyridinium), the putative toxic metabolite of MPTP is also a site I inhibitor. Incubation of hepatocytes with MPP+ similarly potentiated the toxicity of 6-hydroxydopamine, dopamine, and norepinephrine under conditions where MPP+ alone or catecholamines alone did not kill cells. Hepatocytes that had accumulated dopamine from the medium were killed by a subsequent exposure to MPP+ in the absence of a catecholamine in the medium. Hepatocytes that had not been pretreated with dopamine were not affected by the subsequent exposure to MPP+. These data indicated that catecholamines render hepatocytes more susceptible to the toxicity of MPP+ and suggest that the presence of catecholamines in specific neurons in the brain may be related to the selective neurotoxicity of MPTP.

Deciding to terminate treatment: a practical guide for physicians.

Providing house officers and practicing physicians with annotated, concise, practical guidelines for decisions to terminate treatment is the objective of this report. The study selection and data extraction focused on statutes, regulations, court decisions, medicolegal analyses, clinical studies, and position papers addressing termination-of-treatment issues. To foster a systematic approach, we developed a laminated, pocket-sized card containing a series of questions to be asked by any physician confronted with termination-of-treatment decisions. Systematic identification and deliberate assessment of (1) brain death; (2) the nature, extent, cause, prognosis, and reversibility of impairment; (3) the type of treatment to be withheld or withdrawn; (4) the futility of any proposed intervention; (5) the capacity of the patient for health care decision-making; (6) the evidence of patient's wishes; (7) the proper roles of family members, surrogate decision makers, and other health professionals (eg, ethics committees); and (8) applicable policies, ethics, laws, and potential conflicts of interest will enhance efficiency and add value to the decision-making process at the end of life.

Prion infections in Creutzfeldt-Jakob disease and its variants.

Prions (PrP(Sc)) are proteinaceous infectious particles that occur as sporadic (85 percent), infectious (iatrogenic) (5 percent) or hereditary (10 percent) diseases in humans and animals. These unique infectious agents produce a spongiform change in the central nervous system without any inflammation, inclusion bodies or apparent antibody response. A helper (X) protein and genetic predisposition appear to be required to establish the infection, which seems associated with a post-translational change of a normal protein (PrP(C)) encoded by a gene on human chromosome 20. Sporadic human prion disease (Creutzfeldt-Jakob disease) is the most common form of human transmissible spongiform encephalopathy. Nevertheless, it is undoubtedly under-recognized as a result of both low autopsy rates and confusion with other dementing diseases like Alzheimer's disease. Although no therapy is currently available for this infectious dementia, which has a prolonged incubation period, these unfortunate victims should be offered supportive care and postmortem examinations. Universal precautions will protect laboratorians from this infectious, but not contagious, disease.

Common bacteria whose susceptibility to antimicrobials is no longer predictable.

The widespread use of antibiotics has been responsible for the development of numerous problems including the emergence of multidrug resistant bacteria, increased number of nosocomial- and community-acquired infections, less than optimal patient outcome, and increased health care costs. Of equal concern is the emergence of resistance in clinical isolates to antibiotics that were once considered "standard" with predictable in vitro susceptibility patterns. Such resistance has been especially notable in organisms that are commonly encountered in a variety of infections including, Streptococcus pneumoniae, Staphylococcus aureus. Enterococci, Klebsiella pneumoniae, and Escherichia coli. It is important for the clinical microbiology laboratory to provide the practicing clinician with accurate and timely antimicrobial susceptibility information which requires the application of standardized and approved in vitro testing methods. The laboratory also serves as a sentinel by maintaining an active monitoring and surveillance program in which current in vitro susceptibility patterns can be compared with local, regional, and national data bases.