Record linked retrospective cohort study of 4.6 million people exploring ethnic variations in disease: myocardial infarction in South Asians

Background  

Law and policy in several countries require health services to demonstrate that they are promoting racial/ethnic equality. However, suitable and accurate data are usually not available. We demonstrated, using acute myocardial infarction, that linkage techniques can be ethical and potentially useful for this purpose.     

Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma.

PURPOSE: Mantle cell lymphoma (MCL) is characterized by a t(11;14) resulting in overexpression of cyclin D1 messenger RNA. This study tested whether temsirolimus (previously known as CCI-779), an inhibitor of the mammalian target of rapamycin kinase that regulates cyclin D1 translation, could produce tumor responses in patients with MCL. PATIENTS AND METHODS: Patients with relapsed or refractory MCL were eligible to receive temsirolimus 250 mg intravenously every week as a single agent. Patients with a tumor response after six cycles were eligible to continue drug for a total of 12 cycles or two cycles after complete remission, and were then observed without maintenance. RESULTS: Thirty-five patients were enrolled and were assessable for toxicity; one patient had MCL by histology but was cyclin D1 negative and was ineligible for efficacy. The median age was 70 years (range, 38 to 89 years), 91% were stage 4, and 69% had two or more extranodal sites. Patients had received a median of three prior therapies (range, one to 11), and 54% were refractory to the last treatment. The overall response rate was 38% (13 of 34 patients; 90% CI, 24% to 54%) with one complete response (3%) and 12 partial responses (35%). The median time-to-progression in all patients was 6.5 months (95% CI, 2.9 to 8.3 months), and the duration of response for the 13 responders was 6.9 months (95% CI, 5.2 to 12.4 months). Hematologic toxicities were the most common, with 71% (25 of 35 patients) having grade 3 and 11% (four of 35 patients) having grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reductions but was of short duration, typically resolving within 1 week. CONCLUSIONS: Single-agent temsirolimus has substantial antitumor activity in relapsed MCL. This study demonstrates that agents that selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit. Further studies of this agent in MCL and other lymphoid malignancies are warranted.     

Case Studies in Heparin-Induced Thrombocytopenia

Type II heparin-induced thrombocytopenia (HIT) is an immunological disorder characterized by antibodies to heparin-platelet factor 4 complexes and a high risk of thrombotic complications. Here, we present illustrative case histories to educate the reader on evaluation and management of this complex syndrome. Cases include typical and unusual presentations of the syndrome, and commonly encountered problems and pitfalls of therapy. Major points illustrated are, (1) occurrence of HIT with any dose or form of heparin; (2) misperceptions on the diagnostic criteria; (3) correct (thrombin inhibitors) and incorrect (platelet transfusions and warfarin) management; (4) influence of management strategy on clinical outcomes; (5) severity of the syndrome; and (6) potential for both anamnestic response to heparin and disappearance of HIT antibodies over time. Effective therapy of HIT involves both the prompt recognition of the syndrome and its proper management.