Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice.

BACKGROUND: Macrocytic anaemia (MCV ≥ 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. METHODS: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. RESULTS: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. CONCLUSION: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice.

The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia.

BACKGROUND: Serum ferritin is the best single laboratory test to diagnose iron deficiency anemia (IDA). Ferritin levels <20 µg/L are highly specific for IDA, and ferritin levels >100 µg/L usually exclude IDA. However, ferritin concentrations between 20 and 100 µg/L are often inconclusive. The objective of this study was to improve the diagnosis of IDA when ferritin levels are inconclusive. METHODS: We evaluated the predictive performance of classic (ferritin, mean corpuscular volume, transferrin and serum iron) and modern [reticulocyte hemoglobin content, serum transferrin receptor and soluble transferrin receptor (sTfR)/log(ferr)] iron status parameters to diagnose IDA in 2084 anemic, non-hospitalized patients. The results were validated in an independent cohort of 274 anemic patients. RESULTS: In our study population, 29% (595 patients) of the patients had a ferritin level between 20 and 100 µg/L, hampering diagnosis of IDA. None of the classic or modern parameters was capable of completely separating the IDA population from the non-IDA population. However, using a new parameter, the transferrin/log(ferritin) ratio, the IDA and non-IDA populations can be completely separated. At a cut-off value of 1.70, the transferrin/log(ferritin) ratio indicates IDA in 29% of the patients with inconclusive ferritin levels. CONCLUSIONS: The transferrin/log(ferritin) ratio is a practical new tool that improves diagnosis of iron deficiency when ferritin levels are inconclusive.

Carfilzomib, Pomalidomide, and Dexamethasone As Second-line Therapy for Lenalidomide-refractory Multiple Myeloma.

This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide.

Screening for gastrointestinal malignancy in patients with iron deficiency anemia by general practitioners: an observational study.

BACKGROUND: The prevalence of iron deficiency anemia (IDA) is 2-5% in men and postmenopausal women in the developed world. IDA is commonly caused by chronic gastrointestinal blood loss, and a thorough examination of the gastrointestinal tract must be standard practice. OBJECTIVE: To retrospectively study endoscopic evaluations of patients from general practitioners diagnosed with IDA in a peripheral hospital laboratory in order to determine the cause of IDA and the number of gastrointestinal malignancies. MATERIAL AND METHODS: We retrospectively evaluated all patients with IDA diagnosed in a peripheral hospital laboratory by the general practitioner in the region of our hospital from 1 January 2004 until 31 December 2005. We included women older than 50 and men 18 years and older without a history of IDA in the previous 2 years. RESULTS: In 2 years, 287 patients were newly diagnosed with IDA in our hospital laboratory. Only 90 (31%) patients were endoscopically evaluated within 4 months. Gastrointestinal endoscopy revealed at least one lesion potentially responsible for blood loss in 41 of 90 (46%) patients. The most common lesions identified by gastroduodenal endoscopy were erosive esophagitis, gastritis and duodenitis (14%). Cancer was the most commonly detected lesion in the colon, accounting for 17 of 21 colonic lesions explaining IDA. In total, gastrointestinal malignancy was diagnosed in 2% of screened patients. Factors determining the decision for endoscopic screening were lower hemoglobin level, lower ferritin level and male gender. CONCLUSION: In our retrospective study of patients with IDA, only 31% received any form of endoscopic evaluation. In general practice, IDA is investigated suboptimally, and interventions other than the issuing of guidelines are needed to change practice.

Validating diagnostic tests, correct and incorrect methods, new developments.

BACKGROUND: Clinical developments of new treatments are impossible without adequate diagnostic tests. Several working parties including the Consolidated Standard Randomized Trials (CONSORT) movement and the Standard for Reporting Diagnostic Accuracy (STARD) group have launched quality criteria for diagnostic tests. Particularly, accuracy-, reproducibility- and precision-assessments have been recommended, but methods of assessment have not been defined so far. OBJECTIVE: To summarize correct and incorrect methods and new developments for that purpose. RESULTS AND CONCLUSIONS: A diagnostic test can be either qualitative like the presence of an elevated erythrocyte sedimentation rate to demonstrate pneumonia, or quantitative like ultrasound flow velocity to estimate invasive electromagnetic flow velocity. Qualitative diagnostic tests can be assessed for -accuracy using sensitivity / specificity / overall accuracy, and receiver operated (ROC) curves, -reproducibility using Cohen's kappas, -precision using confidence intervals of sensitivity / specificity / overall accuracy. Quantitative diagnostics tests can be assessed for -accuracy using a linear regression line (y = a + b x) and testing a = 0.00 / b = 1.00, -reproducibility using duplicate standard errors, repeatability coefficients or intraclass correlations, -precision by calculating confidence intervals. Improved confidence intervals can be obtained by data modeling. A significant linear correlation between the diagnostic test and the gold standard test does not correctly indicate adequate accuracy. A small mean difference between repeated measures or a significant linear relationship between repeated measures does not indicate adequate reproducibility. New developments include continuous ROC curves, intraclass correlations, and Bland-Altman agreement tests for the accuracy assessments of quantitative diagnostic tests.