The link between lower serum magnesium and kidney function in patients with diabetes mellitus Type 2 deserves a closer look.

INTRODUCTION: We previously reported that lower serum magnesium levels [Mg2+] can be associated with more rapid decline in renal function in patients with diabetes mellitus Type 2 (DM2). We now report long-term renal outcomes of the same patient cohort. MATERIALS AND METHODS: Most recent serum creatinine (SCr) and routine urinary analyses (RUA) for the 550 DM2 patients from our original study were collected. DATA ANALYSIS: Patients with follow-up data were stratified according to the original study: Group 1 had initial [Mg2+] < or = 1.6 - 1.8 mg/dl, Group 3 > 1.8 - 2.0 mg/dl and Group 4 > 2.0 mg/dl. The change in renal function was defined by the ratio of the most recent to the initial SCr as well as slope of 1/SCr-versus-time. Any level of proteinuria detected from RUA provided evidence for overt proteinuria. Renal outcomes were analyzed for each defined patient group. RESULTS: SCr were available for 329 out of 550 patients (59.8%). The duration of follow-up ranged from 93.8 +/- 23.4 - 99.4 +/- 22.4 months among 5 groups. The ratios of the most recent to the initial SCr were 1.54 +/- 1.01, 1.28 +/- 0.51, 1.26 +/- 0.57 and 1.09 +/- 0.29 for Groups 1 - 4, respectively; where the differences between Groups 1, 2 and 3 against Group 4 were significant (p = 0.02, 0.001 and 0.007, respectively). Accordingly, the mean slope of 1/SCr-versus-time was the best for Group 4. RUA were available for 176 patients: 22.2%, 9%, 7.3% and none from Groups 1 to 4, respectively, developed overt proteinuria. CONCLUSION: Our follow-up data suggest a link between low [Mg2+] and worse renal outcomes in DM2 patients.

Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2.

AIMS: Hypomagnesemia has been implicated in adversely affecting diabetic complications. This is a retrospective study designed to determine whether there is any association between serum magnesium concentration [Mg2+] and the rate of renal function deterioration, as determined by the slope of serum creatinine reciprocals versus time (1/SCr-vs-t), in patients with diabetes mellitus type 2 (DM2). MATERIALS AND METHODS: DM2 patients without known kidney disease seen at Olive View-UCLA Medical Center for any reason during January-March 2001 were included. For each patient, all available data from our electronic database for [Mg2+], hemoglobin A(1C) (HbA(1C), serum creatinine (SCr), lipid profiles, routine urinary analysis, as well as history of hypertension and pharmacy profiles were retrieved. The average of all parameters obtained and linear regression analyses for the slope of 1/SCr-vs-t plot were performed for each patient. Patients were stratified by gender and divided into four groups based on increasing [Mg2+]. Correlations between each parameter including the slope of 1/SCr-vs-t and the four magnesium groups were analyzed. RESULTS: 252 males and 298 females with a mean follow-up of 62.6 +/- 22.5 months were included. Patients belonging to lower [Mg2+] groups for both genders had significantly worse slopes of 1/SCr-vs-t plot independent of the presence of hypertension and use of ACEI/ARB, diuretics, HMG-CoA enzyme inhibitors or aspirin. In a multivariate regression analysis controlling for age, HbA(1C) and various components of the lipid profile, [Mg2+] remained an independent predictor for the slope of 1/SCr-vs-t. A trend for worse proteinuria based on routine urinary analysis was observed among patients belonging to the lowest [Mg2+] group. CONCLUSIONS: Lower [Mg2+] is associated with a faster renal function deterioration rate in DM2 patients.

Correlation between self-reported adherence to highly active antiretroviral therapy (HAART) and virologic outcome.

The Patient Medication Adherence Questionnaire Version 1.0 (PMAQ-V1.0) is a patient-reported adherence instrument to assess medication-taking behaviors and identify barriers to adherence with antiretroviral therapy. To assess the correlation between adherence and virologic outcome, the PMAQ-V1.0 was administered to 194 antiretroviral-experienced adults with HIV infection enrolled in a 16-week evaluation of protease inhibitor-containing regimens featuring a lamivudine/zidovudine combination tablet. At baseline, plasma HIV-1 RNA levels were less than 10,000 copies/mL and CD4(+)-cell counts were equal to or greater than 300 x 10(6)/L; patients had been receiving a conventional regimen of lamivudine + zidovudine (separately) plus a protease inhibitor for at least 10 weeks immediately prior to the study. Forty-eight percent of patients who reported missing at least one dose of a nucleoside reverse-transcriptase inhibitor (NRTI) during the study had detectable plasma HIV-1 RNA, compared with 26% of patients who reported no missed doses (P = .002). Patients who missed at least one dose of an NRTI or protease inhibitor were 2.5 times more likely to have quantifiable HIV-1 RNA than those who reported no missed doses. Patients who reported fewer barriers and more motivators to adherence had better virologic outcomes (P = .001). Several dimensions of the PMAQ-V1.0 did not function as well as hypothesized. In this study, self-reported adherence derived from the PMAQ-V1.0 predicted virologic outcomes, but further refinement of the dimensions appears warranted.

Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection.

To assess the value of phenotypic drug susceptibility testing as a predictor of antiretroviral treatment response in human immunodeficiency virus (HIV)-infected people, drug susceptibility testing was performed retrospectively on plasma samples collected at baseline in a cohort of 86 antiretroviral-experienced, HIV-infected people experiencing treatment failure and initiating a new antiretroviral treatment regimen. Two separate criteria for reduced drug susceptibility were evaluated. In multivariate analyses, phenotypic susceptibility was an independent predictor of time to treatment failure (adjusted hazards ratio [HR], 0.70; 95% confidence interval [CI], 0.55-0.90; and adjusted HR, 0.76; 95% CI, 0.61-0.95, with reduced drug susceptibility cutoffs defined as 4.0-fold and 2.5-fold higher than reference virus IC(50) values, respectively). Previous protease inhibitor experience was also a significant independent predictor. Notably, drug susceptibility predicted on the basis of treatment history alone was not predictive of time to treatment failure. In this cohort, phenotypic testing results enhanced the ability to predict sustained long-term suppression of virus load.

Impact of zidovudine-based triple combination therapy on an AIDS drug assistance program.

A static deterministic model was used to estimate the effect of the shift to a triple combination therapeutic standard on the annual AIDS Drug Assistance Program (ADAP) budget, total medical care expenditures, and population health outcomes for New York (NY) state ADAP enrollees. The model used opportunistic disease incidence data from the Multicenter AIDS Cohort Study (MACS) and other studies. Costs of treating opportunistic infections (OIs) and other HIV complications with each type of therapy were derived from treatment algorithms and standard unit costs. CD4+ cell counts were used as an index of need for OI prophylaxis and for determining OI incidence. Treatment with zidovudine-based combination therapy has been shown to increase CD4+ cell counts and reduce OI incidence. The model estimated that a change from monotherapy to triple therapy would have increased NY ADAP budget expenditures per enrollee by 115%. However, total medical system costs per ADAP enrollee (including ADAP costs) would decrease by 0.4% in the base case as a result of reduction in OIs and other HIV sequelae and associated costs. Results are sensitive to the assumed percentage of people taking combination therapy as well as to the assumptions made about the impact of the combination therapy on CD4+ cell count. Total ADAP budget impacts will depend on the growth in ADAP enrollment as a result of the availability of more effective therapies. In conclusion, this model demonstrates how access to newer, more effective HIV drug treatments can reduce the costs of treating OIs and provide major health benefits for ADAP enrollees.

Quality of life. 2. Economic analysis of drug therapies.

In 1990, health care expenditures in the United States reached $666.2 billion, 12.2% of the gross domestic product (GDP). It is projected for the year 2000, the USA will spend $1.6 trillion for health care which will be comparable to 16.4% of that year's GDP. As a result of the rapid increase in costs of health care and limited resources available, patients, third-party payers and the government have initiated and implemented more rigid cost control measures. Economic analyses can help ensure the efficient use of health care dollars in areas such as drug therapy. The four methodologies available are cost-benefit analysis, cost-effectiveness analysis, cost-minimization analysis and cost-utility analysis. This article reviews methods and provides examples from the medical literature. These tools can assist care providers in determining which treatments are most cost-effective.

Projections of the medial terminal nucleus of the accessory optic system upon pretectal nuclei in the pigmented rat.

The projections of the medial terminal nucleus (MTN) of the accessory optic system (AOS) upon pretectal nuclei have been studied in pigmented rats by means of (i) the anterograde transport of 3H-leucine with the use of light autoradiography and (ii) the retrograde transport of horseradish peroxidase (HRP). Injections of 3H-leucine largely restricted to the MTN and minimally involving adjacent ventral midbrain structures, produced heavy terminal axonal labeling within the ipsilateral nucleus of the optic tract (NOT) and the dorsal terminal nucleus (DTN) of the AOS. Terminal labeling was observed in all superficial portions of the NOT, except for a small ventromedial segment in the rostral two thirds and a larger medial segment in the caudal one third of this nucleus. Thus the MTN-NOT projections we describe entirely overlap the retinal-NOT projection and partially overlap the visual cortical-NOT, as reported by others. Within the DTN, the dense terminal fields covered the entire nucleus. After postinjection survival times of 3-7 days, the pattern of axonal labeling showed that the MTN-NOT projection consisted of three bundles: (i) a superficial mesencephalic bundle coursing within the superior fasciculus, posterior fibers of the AOS which enters the caudal portions of the NOT and the DTN; (ii) a deep mesencephalic bundle that traversed the midbrain tegmentum dorsolaterally, also reaching the caudal one-half of the NOT and all of the DTN; and (iii) a mesodiencephalic bundle that passed first laterally through midbrain tegmentum and then dorsally through lateral thalamus to enter the rostral one-half of the NOT. Pretectal injections of HRP that invade the NOT and DTN produced retrograde labeling of most (ca. 75%) of the neurons of the ipsilateral MTN, without labeling the adjacent substantia nigra or ventral tegmental area. This finding confirms our autoradiographic data by showing that the MTN provides the major, ventral tegmental projection to the NOT and DTN. The present finding of a MTN-NOT projection, combined with available anatomical and physiological data, suggests that the MTN may play a more significant role in visual-vestibular aspects of oculomotor control than formerly thought.