Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes

OBJECTIVE: Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial. RESEARCH DESIGN AND METHODS: A total of 268 unselected U.K. Caucasian subjects diagnosed at ages 18-45 years and not treated with permanent insulin for < or =6 months were studied. All subjects underwent clinical assessment and screening for GAD antibodies (GADA) and tyrosine phosphatase IA-2 antibodies (IA-2A). Screening for a common mutation in the hepatocyte nuclear factor-1 alpha (HNF-1 alpha) gene and the common mitochondrial mutation was performed in the antibody-negative subjects. Subjects without insulin resistance were selected for sequencing of the HNF-1 alpha gene. RESULTS: A specific etiology was defined in 11.6% of the 268 subjects and in 24.7% of the lean subjects. Twenty-six subjects (9.7%) were positive for a beta-cell antibody, one subject had familial partial lipodystrophy and the lamin A/C mutation R482W, and two subjects had the mitochondrial mutation A3243G. Two of 15 selected subjects had HNF-1 alpha mutations, the novel missense mutation A501T, and the previously reported R583Q. CONCLUSIONS: This unselected series shows that there is considerable heterogeneity in apparent YT2D. beta-Cell autoantibodies should be performed in all those presenting at ages 18-45 years. Genetic investigations can be targeted to phenotypically defined subjects. The finding of a specific etiology will allow individualization of management and give patients valuable information about their condition.     

Effect of human immunodeficiency virus on intensive care unit outcome of patients with Guillain-Barré syndrome

OBJECTIVES: The primary objective of this study was to investigate the effect of human immunodeficiency virus (HIV) infection on the outcome of patients admitted to the intensive care unit (ICU) with severe Guillain-Barré syndrome (GBS) requiring mechanical ventilation. A secondary objective was to compare the clinical and laboratory features of HIV-seronegative and HIV-seropositive patients admitted to the ICU with severe GBS. DESIGN: Retrospective chart review. SETTING: Two tertiary, academic hospitals in Johannesburg, South Africa. MATERIALS AND METHODS: The case records of all patients admitted to the ICU with GBS between January 1995 and June 2002 were reviewed. Patients were included if their HIV status was known and if they had clinical features, electrophysiologic studies, and cerebrospinal fluid analyses consistent with GBS. Demographic data, days in ICU, days ventilated, CD4 T-lymphocyte counts (in the HIV group), cerebrospinal studies, infection rate, and mortality data were analyzed. RESULTS: A total of 13 patients met the inclusion criteria: seven were HIV seronegative and six were HIV seropositive. The median age in the HIV group was 34.5 yrs, compared with 47 yrs in the non-HIV group. There was no significant difference between the two groups in days spent in the ICU or days ventilated. There were no significant differences in cerebrospinal studies, electrophysiologic studies, and blood culture-positive infections between the two groups. All patients received intravenous immunoglobulin (0.4 g/kg/day for 5 days). There was one death in the HIV-seropositive group and no deaths in the HIV-seronegative group. The median CD4 T-lymphocyte count in the HIV group was 322.5 x 106 cells/L. CONCLUSION: HIV is commonly associated with GBS in South Africa. The ICU outcome in patients with HIV-associated GBS is similar to HIV-seronegative patients, particularly if the CD4 T-lymphocyte count is greater than 200 x 106 cells/L at admission.     

Effect of standardized orders and provider education on head-of-bed positioning in mechanically ventilated patients

OBJECTIVE: Semirecumbent head-of-bed positioning in mechanically ventilated patients decreases the risk of developing ventilator-associated pneumonia (VAP). The purpose of this study was to determine whether the addition of a standardized order followed by the initiation of a provider education program would increase the frequency with which our patients were maintained in the semirecumbent position. DESIGN: Prospective, pre-, and postintervention observational study. SETTING: A tertiary care, U.S. Army teaching hospital. PATIENTS: Mechanically ventilated medical and surgical intensive care unit patients. INTERVENTIONS: The first intervention involved the addition of an order for semirecumbent head-of-bed positioning to our intensive care unit order sets. This was followed 2 months later with a second intervention, which was a nurse and physician education program emphasizing semirecumbent positioning. MEASUREMENTS AND MAIN RESULTS: Data regarding head-of-bed positioning were collected on 100 patient observations at baseline and at 1 and 2 months after each of our interventions. The mean angle of head of bed increased from 24 +/- 9 degrees at baseline to 35 +/- 9 degrees (p <.05) 2 months after the addition of the standard order. The percentage of observations with head of bed >45 degrees increased from 3% to 16% 2 months after the standardized order (p <.05). Two months after our provider education program, the mean angle of the head of bed was 34 +/- 11 degrees and the percentage of patients with head of bed >45 degrees was 29% (p = NS compared with values after the first intervention). Data collected 6 months after completion of our education programs showed that these improvements were maintained. CONCLUSIONS: Standardizing the process of care via the addition of an order specifying head-of-bed position significantly increased the number of patients who were placed in the semirecumbent position. In an era of cost-conscious medicine, interventions that utilize protocols and education programs should be emphasized.     

A prospective study on the implications of a base deficit during fluid resuscitation

An excessive base deficit (BD) and elevated serum lactate are increasingly recognized as important markers of a malperfusion state during the resuscitation of thermally injured patients. In a previous retrospective study, we found that patients with a BD less than -6 mmol/l during fluid resuscitation developed more severe systemic inflammatory response syndrome (SIRS), more frequent acute respiratory distress syndrome (ARDS), and more severe multiple organ dysfunction syndrome (MODS). The object of this study was to reexamine prospectively the relationship between the BD during fluid resuscitation and the subsequent development of SIRS, ARDS, and MODS by undertaking a prospective observational study of a cohort of consecutive burn patients. Analysis was completed on 38 patients with a mean age of 39 +/- 17 years and a mean %TBSA burn of 36 +/- 15%. The mean BD in the first 24 hours was less than -6 mmol/l in five patients (BD24 < -6 group), and was greater than -6 mmol/L in 33 patients (BD24 > -6 group). Patients in both groups were resuscitated to nearly identical endpoints of urinary output (1.2 ml/kg/hr in the BD24 < -6 group vs 1.3 ml/kg/hr in the BD24 > -6 group). Patients in the BD24 < -6 group had a trend toward a greater number of SIRS signs on the first postburn day, had a significantly higher incidence of ARDS (P =.02), and had significantly more severe MODS (P <.001) than patients in the BD24 > -6 group. The results concur with those of our previous retrospective study. Despite resuscitation to an acceptable urinary output, some burn patients develop a more extreme BD and go on to experience more severe organ dysfunction than do patients who do not generate a BD. The effect of specific correction of the BD during fluid resuscitation is not known at this time.     

Rescreening in cervical cytology for quality control. When bad data is worse than no data or what works, what doesn't, and why

The currently mandated methods to measure the sensitivity of Papanicolaou smear interpretation (including the 5-year look back and review of 10% of negative smears) are misleading. They do not allow one to measure the true sensitivity of the test and allow only a small fraction of errors to be detected and corrected. Rapid prescreening and automated screening are the only methods that seem practically feasible, and will allow the sensitivity of the method to be measured on a routine basis, and, thereby allow a reduction in overall errors. Although emerging technologies, such as HPV testing, may allow alternative methods of measuring sensitivity, the most appropriate way to use and interpret these data in this context are not yet fully developed. Unfortunately, at present there seems to be little desire to change the way things are done, and, therefore, to accurately measure sensitivity in cervical cytology. The first task that needs to be undertaken in fixing a problem is to admit that one exists. At present, most laboratory directors believe that their own laboratory is performing satisfactorily. They may well be, although the laboratories lack an analytic method to demonstrate this, and, therefore, the need for better QA methods does not seem to be acute. There is some educational value to the currently practiced and mandated performance measures, the 5-year look back and review of 10% of negative smears. Most laboratory directors seem to be happy with their QA methods and are not concerned that the data that are derived from the 10% review of negative slides does not reflect their actual sensitivity of screening in any meaningful way. Unfortunately, the forces that are currently in place in the United States ensure that accurate measures of the sensitivity of cervical cytology interpretation are unlikely to be implemented beyond the level of individual experimentation. As long as the expectation of cytologists is that the error rates are significantly less than they actually are; as long as there is significant legal and financial risk to actually measuring the true sensitivity; and as long as fictitious measures of performance are not only advocated but mandated; the confluence of incentives will ensure that the true sensitivity of the test will never be measured on a routine basis. Despite all of this, it is possible that cervical cytology screening may, in fact, already be performing at an optimal level. Being able to measure this operating performance may not effect any improvement to the overall process. The ultimate arbiter in this debate will always be the demonstration of a reduction of cervical cancer morbidity and mortality with any new measure implemented. At the present time, there is only one solution to the quality control issue; a force from outside the system must change the balance of the aforementioned incentives. The promise of data from European experiences with rapid rescreening may show that this method is effective and accurate. Such data might make the current methods that are in use in the United States more open to change. So yes, the answer is that "bad" data may be worse than no data at all. The bad data that we have been collecting for more than a decade is as effective a trap as anyone could have devised to ensure that actually measuring the performance of cervical smear interpretation does not happen. The only question that remains is, "How we will be able to escape?"     

Extracorporeal membrane oxygenation as a bridge to cardiac transplantation in a patient with cardiomyopathy and hemophilia A

OBJECTIVE: To report the use of extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation in a patient with hemophilia A and dilated cardiomyopathy. DESIGN: Case report. INTERVENTIONS AND RESULTS: During ECMO factor VIII concentrate was administered to maintain a factor VIII level close to 50% of normal control both to decrease the risk of bleeding and to allow standard anticoagulation with heparin. The patient developed an inhibitor to exogenous factor VIII during hospitalization, which was successfully managed with a high-dose continuous infusion of factor VIII during ECMO, the transplant operation, and the postoperative period. CONCLUSIONS: We report the successful use of ECMO as a bridge to cardiac transplantation in a patient with hemophilia A and low-level factor VIII inhibitors.