Clinical utility of assays of glycosylated haemoglobin and serum fructosamine compared: use of data on biological variation

Assessment of the relative clinical usefulness of glycosylated haemoglobin (HbA1) and serum fructosamine is complicated by their markedly different half-lives. They have therefore been compared using a number of indices derived from data on biological variation, as applied in a study of blood glucose control in newly diagnosed diabetic patients. The within-subject (CVI) and between-subject (CVG) variation of fructosamine and HbA1 were assessed in 8 stable diabetic patients. A slightly smaller relative change, or critical difference, is required between serial HbA1 results than between fructosamine results before a significant change can be said to have occurred. The heterogeneity of within-subject variance is also less for HbA1, rendering the critical difference more generally applicable. HbA1 may therefore be more appropriate for long-term monitoring. Monitoring of blood glucose control of a group of 26 newly diagnosed diabetic patients before the commencement of therapy and 1, 2, and 3 months later by serum fructosamine or HbA1 provided very similar information. Fructosamine responds more rapidly with changes of blood glucose control. However, whether this confers any clinical advantage will depend upon the frequency of testing.     

Tmax: An Unconfounded Metric for Rate of Absorption in Single Dose Bioequivalence Studies

Purpose. While peak drug concentration (Cmax) is recognized to be contaminated by the extent of absorption, it has long served as the indicator of change in absorption rate in bioequivalence studies. This concentration measure per se is a measure of extreme drug exposure, not absorption rate. This paper redirects attention to Tmax as the absorption rate variable. Methods. We show that the time to peak measure (Tmax), if obtained from equally spaced sampling times during the suspected absorption phase, defines a count process which encapsulates the rate of absorption. Furthermore such count data appear to follow the single parameter Poisson distribution which characterizes the rate of many a discrete process, and which therefore supplies the proper theoretical basis to compare two or more formulations for differences in the rate of absorption. This paper urges limiting the use of peak height measures based on Cmax to evaluate only for dose-dumping, a legitimate safety concern with, any formulation. These principles and techniques are illustrated by a bioequivalence study in which two test suspensions are compared to a reference formulation. Results. Appropriate statistical evaluation of absorption rate via Tmax supports bioequivalence, whereas the customary analysis with Cmax leads to rejection of bioequivalence. This suggests that the inappropriate use of Cmax as a surrogate metric for absorption rate contributes to the unpredictable and uncertain outcome in bioequivalence evaluation today.     

Unusual presentation of a dermoid cyst in the ischiorectal fossa. Magnetic resonance imaging and ultrasound appearances

The ischiorectal fossa may give rise to a wide variety of pathological entities, although it is composed of relatively few structures. Developmental cysts are included among the list. Large epidermoid cysts in the ischiorectal fossa have been previously described (Fujimoto et al., Clin Imaging 17:146–148, 1993; Ng et al., Can J Surg 49:435–436, 2006). However, to the best of our knowledge, there is no published case in the English literature of a dermoid cyst within the ischiorectal fossa. Using magnetic resonance (MR) imaging and a subsequent ultrasound-guided biopsy, we were able to offer a focused differential that included a dermoid cyst within the ischiorectal fossa in a 55-year-old man presenting with a painful mass on the buttocks. Hair and fatty components were obtained by targeted ultrasound-guided biopsy. On MR imaging, the mass was seen to be well circumscribed and registered a heterogeneous T1-weighted signal that corresponded to layers of fat and debris on short-tau inversion recovery (STIR) imaging. A well-defined ball of fat was noted centrally within the lesion, with a speckled low T1 and low T2 signal within it. Hair admixed with fat was obtained from it by targeted ultrasound-guided biopsy. There was no enhancement of the lesion after administration of gadolinium. On ultrasound, the lesion was well circumscribed and heterogeneous; the echogenic area corresponded to the fat signal seen on magnetic resonance imaging (MRI). The lower level echoes within the lesion corresponded to the debris seen on MRI. The central rounded area of speckling, registering fine posterior shadowing corresponded to the hairy contents obtained by the targeted ultrasound-guided biopsy. A differential diagnosis of all lipomatous lesions was included in the pre-biopsy report: fat necrosis within a lipoma; well-differentiated liposarcoma; myxoid liposarcoma and dermoid cyst. Histopathological diagnosis following complete surgical resection was that of a dermoid cyst.     

Left ventricular ejection fraction and volumes from gated blood-pool SPECT: comparison with planar gated blood-pool imaging and assessment of repeatability in patients with heart failure.

Gated blood-pool SPECT (GBPS) has several potential advantages over planar radionuclide ventriculography (PRNV), including the possibility of greater repeatability of left ventricular ejection fraction (LVEF) and the noninvasive calculation of left ventricular end-systolic volume and left ventricular end-diastolic volume (LVEDV). The aim of this study was to assess the repeatability of LVEF and LVEDV from GBPS and to compare LVEF with those from PRNV. METHODS: Fifty patients underwent PRNV and GBPS, 23 of whom also had repeated studies in the same session. GPBS studies were processed using the Cedars Sinai Quantitative Blood-Pool SPECT (QBS) software that automatically calculates LVEF and LVEDV. Automatic processing with QBS was successful in 70% of the GBPS studies, with the remaining studies processed using the manual option in QBS. All PRNV studies were processed using a manual processing technique. RESULTS: Comparison of LVEF from PRNV and GBPS yielded a correlation coefficient of 0.80. Bland-Altman analysis demonstrated a mean difference of 0.74% +/- 7.62% (mean +/- SD) between LVEF from the 2 techniques. The 95% limits of agreement are therefore -14.50% to +15.98%. The correlation between repeated measurements was 0.87 for GBPS and 0.95 for PRNV. Bland-Altman analysis revealed poorer repeatability for GBPS (95% limits of agreement, -9.63% to +14.97% vs. -4.66% to +5.92%; P = 0.003). The mean LVEDV was 198 +/- 94 mL, with a mean difference of 9 +/- 47 mL between repeated measurements. The 95% limits of agreement are therefore -85 to +103 mL. CONCLUSION: GBPS provides a less repeatable measurement of LVEF than PRNV. Repeatability of LVEDV measurements from GBPS is poor.     

Coeliac disease and bone mineral density in adult female patients.

A cross sectional study was undertaken to examine the relationship between coeliac disease and bone mineral density. The 135 female coeliac patients registered on the database of the Department of Gastroenterology at Hull Royal Infirmary were approached by letter, advising them of a potential risk of osteoporosis and inviting them to undergo bone densitometry. A total of 81 registered women (60%) attended the Osteoporosis Laboratory, Princess Royal Hospital and underwent dual energy x ray absorptiometry at the lumbar spine (L2-L4) and femoral neck. Historical data relating to the time of diagnosis and adherence to a gluten free diet were obtained. A control group was selected from the local normal population and was first matched for height, weight, and menopausal status. Postmenopausal patients were then further matched to controls of equivalent menopausal age. In coeliac patients, bone mineral density expressed in g/cm2 as mean (SD) was significantly lower at the lumbar spine (1.076 (0.186)) than in the control group (1.155 (0.143), p < 0.001). This was also the case at the femoral neck (0.887 (0.142) versus 0.965 (0.127), p < 0.001). When the coeliac patients were stratified by menopausal status, it was found that femoral neck bone mineral density was significantly below control values in both premenopausal and postmenopausal women. Spinal bone mineral density exhibited a significant decrement only in the postmenopausal group. The age at diagnosis of coeliac disease and adherence to a gluten free diet did not influence bone mineral density at either hip or spine. These results confirm coeliac patients' higher risk of osteopenia. Coeliac disease should be added to the list of medical conditions which constitute an indication for bone densitometry in order that the individual risk of osteoporosis related fracture may be determined.