End-digit preference in general practice: a comparison of the conventional auscultatory and electronic oscillometric methods

INTRODUCTION: In clinical practice, end-digit preference is a common feature of blood pressure (BP) measurements. A wider use of electronic BP measuring machines could decrease this observer-linked artefact. The purpose of this analysis was to investigate the frequency of end-digit preference and to evaluate the impact of this observer bias on the assessment of the BP control induced in a large group of hypertensive patients treated with a calcium-channel blocker in whom BP was measured either with an automatic device or with a conventional sphygmomanometer. METHODS: Five hundred and four physicians participated in the study and 2199 patients were included. Treatment with lercanidipine was introduced at a dosage of 10 mg and titration to 20 mg was optional according to the physician's decision. BP was assessed at 4 and 8 weeks. To measure BP, physicians could use either a standard mercury sphygmomanometer or a pre-defined validated semi-automatic device (Microlife Average Mode, BP 3AC1-1, Microlife Corporation, Berneck, Switzerland) but they had to use the same method throughout the study. Physicians had to transcribe all BP measurements onto case report forms. RESULTS: Very marked digit preferences were observed for both the conventional and the automatic measurements, being most prominent for the digit "0" (52% and 25%, respectively) followed by a preference for the digit "5" (19% and 15%). The use of the semi-automatic device reduces to a certain extent the frequency of the bias but the problem remains if physicians have to transfer the BP values onto case report forms. The end-digit preference has a major impact on the evaluation of a treatment effect and on the assessment of the percentage of patients achieving target BP in a population. CONCLUSION: These results confirm that end-digit preference remains a serious bias in clinical practice. This bias has important consequences when evaluating the efficacy of a new antihypertensive drug. There is a need for training programmes and quality controls in clinical practice. The development of automatic systems with a direct transfer of BP values from the measuring device to the clinical chart or to the case report form should be encouraged.     

Pharmacokinetic evaluation of losartan

INTRODUCTION: Blockade of the renin-angiotensin system is one of the major therapeutic strategies in the management of patients with essential hypertension, congestive heart failure and diabetic as well as non-diabetic renal diseases. As the first angiotensin II receptor blocker (ARB) on the market, losartan belongs to the most frequently prescribed ARB. AREA COVERED : The present review examines the pharmacokinetics of losartan with a special discussion on the dose of losartan that should be used in clinical practice to obtain the maximal benefits of the drug. Readers are provided with arguments suggesting that the dose of 50 mg losartan is probably too low and that losartan should preferably be prescribed at the dose of 100 mg/day or higher. EXPERT OPINION : Losartan is an effective antagonist of angiotensin II AT(1) receptors which has been shown to provide important clinical benefits in patients with hypertension, congestive heart failure and renal diseases. Losartan should be prescribed at the dose of 100 mg/day and the use of higher doses should be reconsidered in future studies to improve its clinical efficacy.     

C-kit expression in human osteosarcoma and in vitro assays

Biologic agents targeting oncogenes have encourage researchs trying to correlate the role of tyrosine kinase in the pathogenesis of tumours. Osteosarcoma is a high grade aggressive neoplasm with poor survival. Our aim was to investigate c-kit immunoexpression, its prognostic relevance for patients with osteosarcoma, and the effect of imatinib mesylate (STI571) on proliferation and invasion of the human osteosarcoma cell line.A retrospective immu-nohistochemical study was performed on archival formalin-fixed paraffin-embedded specimens from 52 patients with high-grade primary osteosarcoma of extremities treated at the Pediatric Oncology Institute (IOP, GRAAC) and archived in the Department of Pathology, Federal University of São Paulo. Only pre-chemotherapy specimens were analyzed. Strongly stained cytoplasm and membrane cells were taken as positive. Human osteosarcoma cells from line MG-63 were incubated and the inhibitory effect of imatinib mesylate (STI571) on cell proliferation and invasion was studied. In 24 cases (46.15%), c-kit was expressed by the cells and c-kit-positive tumors exhibited lower necrosis post-chemotherapy. No correlation was found between c-kit expression and overall and disease-free survival. Imatinib mesylate decreased the rates of cell growth of osteosarcoma cells in low doses and invasion in high doses C-kit-positive tumors had worse response to chemotherapy and imatinib mesylate can play a role in blocking or decreasing the rate of growth of osteosarcoma cells, but not the invasive capacity of these neoplastic cells. These data suggested that imatinib mesylate could be a therapeutic target of strategies against osteosarcoma tumors. Further studies are necessary to confirm this indication.     

Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy

Epidemiological studies have shown that obesity is associated with chronic kidney disease and end stage renal disease. These studies have used creatinine derived equations to estimate glomerular filtration rate (GFR) and have indexed GFR to body surface area (BSA). However, the use of equations using creatinine as a surrogate marker of glomerular filtration and the indexation of GFR for BSA can be questioned in the obese population. First, these equations lack precision when they are compared to gold standard GFR measurements such as inulin clearances; secondly, the indexation of GFR for 1.73 m(2) of BSA leads to a systematic underestimation of GFR compared to absolute GFR in obese patients who have BSA that usually exceed 1.73 m(2). Obesity is also associated with pathophysiological changes that can affect the pharmacokinetics of drugs. The effect of obesity on both renal function and drug pharmacokinetics raises the issue of correct drug dosage in obese individuals. This may be particularly relevant for drugs known to have a narrow therapeutic range or excreted by the kidney.     

Referral Patterns and Outcomes in Noncritically Ill Patients with Hospital-Acquired Acute Kidney Injury

Summary

Background and objectives

Despite modern treatment, the case fatality rate of hospital-acquired acute kidney injury (HA-AKI) is still high. We retrospectively described the prevalence and the outcome of HA-AKI without nephrology referral (nrHA-AKI) and late referred HA-AKI patients to nephrologists (lrHA-AKI) compared with early referral patients (erHA-AKI) with respect to renal function recovery, renal replacement therapy (RRT) requirement, and in-hospital mortality of HA-AKI.

Design, setting, participants, & measurements

Noncritically ill patients admitted to the tertiary care academic center of Lausanne, Switzerland, between 2004 and 2008 in the medical and surgical services were included. Acute kidney injury was defined using the Acute Kidney Injury Network (AKIN) classification.

Results

During 5 years, 4296 patients (4.12% of admissions) experienced 4727 episodes of HA-AKI during their hospital stay. The mean ± SD age of the patients was 61 ± 15 years with a 55% male predominance. There were 958 patients with nrHA-AKI (22.3%) and 2504 patients with lrHA-AKI (58.3%). RRT was required in 31% of the patients with lrHA-AKI compared with 24% of the patients with erHA-AKI. In the multiple risk factor analysis, compared with erHA-AKI, nrHA-AKI and lrHA-AKI were significantly associated with worse renal outcome and higher in-hospital mortality.

Conclusions

These data suggest that HA-AKI is frequent and the patients with nrHA-AKI or lrHA-AKI are at increased risk for in-hospital morbidity and mortality.     

Danish type gelsolin-related amyloidosis in a Brazilian family: case reports

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systemic amyloidosis showing marked geographic clustering in Finland. The disease is caused by a point mutation, 654G-A, in the gelsolin gene. The Danish-subtype of FAF has been previously described in three families, the patients present clinical findings similar to FAF, and the mutation 654G-T in the gelsolin gene. Three members from two generations of the same family, with familial amyloidosis, were screened for mutations in the GSN gene. Genomic DNA was extracted from peripheral blood lymphocytes and the polymerase chain reaction (PCR) was carried out under standard conditions, using appropriate primers. Sequence analysis showed the presence of a G to T transition at nucleotide 654 of the gelsolin gene. This is the first report of gelsolin-related familial amyloidosis in a Brazilian family, and the result is particularly significant as this pedigree presents an unusual mutation, described previously in three families, with no known Finnish ancestors (Danish type).