Fate of the mate: the influence of delayed graft function in renal transplantation on the mate recipient.

Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of -11.2 mL/min, while the control group had a mean change of -0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these'at-risk'recipients should be developed and tested.

The stability of utility scores: test-retest reliability and the interpretation of utility scores in elective total hip arthroplasty.

PURPOSES: Are utility scores for hypothetical health states stable over time even when the health of the patient changes dramatically? Can investigators who use scores for hypothetical states be confident about the stability of those scores? The first purpose is to assess the stability of standard gamble utility scores for three hypothetical health states describing mild, moderate, and severe osteoarthritis (OA) (test-retest reliability). How should investigators interpret utility scores? The second purpose is to provide evidence on the marker-state approach to assist in interpreting utility scores. BACKGROUND: SG scores for three hypothetical marker states and the patient's current state were obtained at multiple times in a longitudinal study of elective total hip arthroplasty (THA). SG scores for current health increased from a mean of 0.59 pre-surgery to 0.76 post-surgery. METHODS: Test-retest reliability was assessed using the intra-class correlation coefficient (ICC). The effects of time on scores were analysed using an analysis of covariance. RESULTS: At the group level the marker-state scores were stable. Mean scores for mild, moderate, and severe OA were 0.69, 0.61, and 0.41. With respect to test-retest reliability, ICCs varied from 0.49 to 0.62. In general, time did not affect the scores for the three marker states. CONCLUSIONS: Group-level standard gamble scores are stable. At the individual level scores for hypothetical health states are somewhat stable over time. The marker states assist in interpretation indicating that, on average, THA converted moderate OA to better than mild.

Insulin resistance in latent autoimmune diabetes of adulthood.

Insulin resistance in patients with latent autoimmune diabetes of adulthood (LADA) was determined by homeostasis model assessment (HOMA). LADA was identified by a clinical phenotype of type 2 diabetes with antibodies to GAD65 and/or IA-2/ICA512. All patients were managed with insulin therapy. Insulin resistance in LADA was lower than in antibody-negative type 2 diabetes, higher than in normal humans and in recent-onset type 1 diabetes, and similar to that in long-term type 1 diabetes. Mean values for HOMA varied linearly with mean values for BMI, which accounted for much of the insulin resistance in these forms of diabetes. LADA resembles long-term type 1 diabetes with respect to insulin resistance and BMI, but occurs at an older age.

Autoantibodies and HLA susceptibility markers in Canadian first-degree relatives of patients with type 1 diabetes.

We examined the frequencies of autoantibodies to glutamate decarboxylase, GAD65, protein tyrosine phosphatase, IA-2/ICA512, and insulin, and of HLA class II markers in ICA-positive first-degree relatives of patients with type 1 diabetes. Our results indicate that while the presence of HLA susceptibility markers is associated with anti-islet autoantibodies, protective DQB1 markers do not absolutely prevent development of autoantibodies or progression to autoimmune diabetes.

Quadriceps muscle function and fatigue in women with Addison's disease.

In nine patients with Addison's disease (mean +/- SE: 51 +/- 2 years) receiving conventional steroid treatment, and nine age-matched healthy controls (56 +/- 2 years), we investigated maximum voluntary quadriceps force (MVC) and contractile properties evoked with stimulation and central activation both at rest and during a submaximal intermittent fatigue task. The MVC was similar (-3%), but twitch tension (-27%) and central activation were significantly less (-7%), and tetanic half-relaxation time was approximately 40% slower in the patients. Twitch amplitudes were potentiated by 6% in the patients, but unchanged in the control group. The patients self-terminated a submaximal intermittent fatigue protocol (0.6 duty cycle) at approximately 5 +/- 1 min, whereas the controls stopped when they lost 50% of MVC force ( approximately 10 +/- 1 min). Force loss was similar between groups over the first 5 min of the fatigue task. In the patient group, maximal and submaximal relative integrated electromyogram (IEMG) increased significantly in the first minute of fatigue and remained elevated, whereas the controls exhibited a gradual increase in submaximal IEMG with little change in maximal IEMG. These results indicate that conventionally treated Addison's patients have similar MVC strength, but altered contractile properties and decreased endurance compared with controls.

Surveying physicians to determine the minimal important difference: implications for sample-size calculation.

The minimal important difference (MID) is the smallest benefit of treatment that would result in clinicians recommending it to their patients. The MID is necessary to calculate sample size for randomized clinical trials, but its chosen value is often arbitrary. This study set out to determine the practicability of surveying physicians to elicit the MID for clinical trial sample-size calculation. Using a mail survey, we elicited the MID of different physician specialties (family medicine, internal medicine, vascular surgery) for using propranolol to slow abdominal aortic aneurysm (AAA) growth assuming that propranolol was efficacious in this condition. We used different outcome measures (growth rate or proportion of patients requiring surgery) and different methods of data presentation for the proportion of patients requiring surgery (absolute risk reduction or number needed to treat). The MID varied significantly by physician specialty, experience with AAA and propranolol, and the method used to elicit the MID. Consequently, sample-size calculations using these various MIDs varied from 116 to 3015. Future attempts to elicit the MID need to consider carefully who is surveyed, how data are presented, and how opinions are elicited.

Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice.

STUDY OBJECTIVE: To compare quality of life and exercise capacity (primary aim), and drug usage (secondary aim), between groups of patients with irreversible chronic airflow limitation (CAL) who were undergoing theophylline Theo-Dur; Key Pharmaceuticals; Kenilworth, NJ) therapy guided by n of 1 trials or standard practice. DESIGN: Randomized study of n of 1 trials vs standard practice. SETTING: Outpatient departments in two tertiary care centers. PATIENTS: Sixty-eight patients with irreversible CAL who were symptomatic despite the use of inhaled bronchodilators, and who were unsure whether theophylline was helping them following open treatment, were randomized into n of 1 trials (N=34) or standard practice. INTERVENTIONS: The n of 1 trials (single-patient, randomized, double-blind, multiple crossover comparisons of the effect on dyspnea of theophylline vs a placebo) followed published guidelines. Standard practice patients stopped taking theophylline but resumed it if their dyspnea worsened. If their dyspnea then improved, theophylline was continued. In both groups, a decision about continuing or stopping the use of theophylline was made within 3 months of randomization. MEASUREMENTS AND RESULTS: The primary outcomes (the chronic respiratory disease questionnaire [CRQ] and 6-min walk) were measured at baseline, 6 months, and 12 months by personnel blinded to treatment group allocation. No between-group differences (n of 1 minus standard practice) were seen in within-group changes over time (1 year minus baseline) in the CRQ Physical Function score (point estimate on the difference, -2.8; 95% confidence limits [CLs], -8.2, 2.5), CRQ Emotional Function score (point estimate on the difference, 0.5; 95% CLs, -4.7, 5.7), or 6-min walk (point estimate on the difference, 8 m; 95% CLs, -26, 44 m). No differences between groups were seen in the secondary outcome of the proportion of patients taking theophylline at 6 and 12 months. In 7 of 34 n of 1 trial patients (21%), dyspnea improved during theophylline treatment compared with placebo treatment. CONCLUSIONS: Using n of 1 trials to guide theophylline therapy in patients with irreversible CAL did not improve their quality of life or exercise capacity, or reduce drug usa e, over 1 year compared to standard practice. Under the objective conditions of an n of 1 trial, 21% of patients with CAL responded to theophylline. There remains a rationale for considering theophylline in patients with irreversible CAL who remain symptomatic despite the use of inhaled bronchodilators, but the use of n of 1 trials to guide this decision did not yield clinically important advantages over standard practice.

A randomized study comparing a patient-directed hypertension management strategy with usual office-based care.

This study aimed to compare the efficacy of a patient-directed management strategy with office-based management in maintaining blood pressure control in patients with chronic stable hypertension using a randomized trial of two months duration. The subjects had chronic stable essential hypertension without secondary causes or unstable cardiovascular disease and were selected through the offices of 11 family physicians and a tertiary care hypertension research unit. Patients were randomly assigned (2:1 ratio) to either a patient-directed management strategy using home blood pressure monitoring to adjust drug therapy if readings consistently exceeded defined limits, or office-based management through physician visits. The primary endpoint was the change from baseline in mean arterial pressure as determined by automatic ambulatory blood pressure monitoring. Secondary endpoints were changes in compliance, quality of life, and health care resource use. Ninety-one potential subjects were screened and 31 were randomized. Subjects in the patient-directed management group employed the drug adjustment protocols appropriately without complications. A significant difference in change in mean blood pressure was observed, favoring the patient-directed management (-0.95 mm Hg and +1.90 mm Hg, respectively, for patient-directed management and office-based management, P = .039). Compliance rates and quality of life scores were not significantly different between groups. Physician visits were more frequent in the patient-directed management group (1.05 v 0.20 visits/8 weeks, respectively, for patient-directed management and office-based management groups, P = .045). A patient-directed hypertensive management strategy may be feasible for patients with chronic stable hypertension. Such a strategy may improve blood pressure control compared with usual office-based care. However, physician visits may be increased using this strategy, at least in the short term.

The Ontario trial of active compression-decompression cardiopulmonary resuscitation for in-hospital and prehospital cardiac arrest.

OBJECTIVE: To compare the impact of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of in-hospital and prehospital victims of cardiac arrest. DESIGN: Randomized controlled trial with blinding of allocation using a sealed container. SETTINGS: (1) Emergency departments, wards, and intensive care units of 5 university hospitals and (2) all locations outside hospitals in 2 midsized cities. PATIENTS: A total of 1784 adults who had cardiac arrest. INTERVENTION: Patients received either standard or ACD CPR throughout resuscitation. MAIN OUTCOME MEASURES: Survival for 1 hour and to hospital discharge and the modified Mini-Mental State Examination (MMSE). RESULTS: All characteristics were similar in the standard and ACD CPR groups for the 773 in-hospital patients and the 1011 prehospital patients. For in-hospital patients, there were no significant differences between the standard (n = 368) and ACD (n = 405) CPR groups in survival for 1 hour (35.1% vs 34.6%; P = .89), in survival until hospital discharge (11.4% vs 10.4%; P = .64), or in the median MMSE score of survivors (37 in both groups). For patients who collapsed outside the hospital, there were also no significant differences between the standard (n = 510) and ACD (n = 501) CPR groups in survival for 1 hour (16.5% vs 18.2%; P = .48), in survival to hospital discharge (3.7% vs 4.6%; P = .49), or in the median MMSE score of survivors (35 in both groups). Exploration of clinically important subgroups failed to identify any patients who appeared to benefit from ACD CPR. CONCLUSIONS: ACD CPR did not improve survival or neurologic outcomes in any group of patients with cardiac arrest.

Endocrine-metabolic function in remission-phase IDDM during administration of cyclosporine.

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of bromocriptine and cyclosporine in insulin dependent diabetes mellitus: results from the Canadian open study.

Although cyclosporine A (Cy-A) is effective in modifying the initial course of newly diagnosed insulin dependent diabetes mellitus (IDDM) it has a number of side effects, particularly renal, which limit its use. In this study we investigated the potential synergistic effects of bromocriptine (BCR) therapy in treating patients with newly diagnosed IDDM. Three groups of patients were treated: (1) fourteen patients on Cy-A who required a decrease in their dose due to elevated creatinine; (2) four newly diagnosed patients whose initial therapy consisted of low dose (5 mg/kg/day) Cy-A and 10 mg/day of BCR; (3) eight patients whose glucagon-stimulated connecting-peptide (C-peptide) levels were greater than 0.3 nmol/l but whose insulin requirements were over 0.3 U/kg/day and whose Cy-A was to be discontinued. The results suggest that there was no statistically significant difference in stimulated C-peptide, glycosylated haemoglobin, daily insulin dose or serum creatinine. However, the trend suggested that BCR may have some protective effect on preserving endogenous insulin secretory capacity, although glycosylated haemoglobin and daily insulin dose increased. The results do not suggest that patients with newly diagnosed IDDM significantly benefit from concurrent BCR and Cy-A therapy.

Induction and pathophysiology of remission of insulin-dependent diabetes mellitus during administration of ciclosporin. London Diabetes Study Group.

Ciclosporin-induced noninsulin-receiving remissions in insulin-dependent diabetes mellitus are associated with enhancement of beta-cell function. Patients in remission show virtually no insulin responses to parenteral glucose, contrasting with substantial responses to mixed meals, indicating effects of nonglucose nutrients and/or enteroinsular mechanisms. Remission is associated with normal insulin sensitivity; loss of insulin sensitivity can lead to relapse. The risks of the treatment call for studies with lower doses, and it is argued that a continuing search for immunomodulatory interventions that enhance and preserve the clinical remission-phase characteristics should be pursued.

The immunocompromised patient.

The number of immunocompromised persons-as well as the importance of family physicians understanding their state-is increasing. In many instances the family physician will first identify or provide day-to-day care for such patients while they live in the community. This article gives an overview of certain aspects of normal host immunity, etiology and mechanisms in immunocompromisation, and outlines techniques for recognition and management of this special group of patients.