Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Vector Control in Oakland’s Homeless Encampments

Homeless encampments are a persistent feature in the city of Oakland, California. Unsanitary conditions in these camps can contribute to large populations of Norway rats and associated vector-borne disease. Alameda County Vector Control Services District has developed a surveillance program for safe and efficient data collection in these encampments. This program includes outreach to residents, effective live-trap ping, ectoparasite collection, vector species suppression, and coordinating with other agencies. The District’s operations around Oakland’s pilot “Tuff Shed” homeless shelter strategy are presented as a case study for Norway rat and Oriental rat flea risk assessment and control

An open multicentre study of tropisetron for cisplatin-induced nausea and vomiting

OBJECTIVES: (i) To assess the efficacy and tolerability of tropisetron when used for acute and delayed cisplatin-induced emesis. (ii) To investigate whether dexamethasone added to tropisetron improves the control of emesis for patients who do not achieve a complete response to tropisetron alone. (iii) To assess sex of the patient and alcohol intake as prognostic factors for nausea and vomiting. DESIGN: A prospective open label phase II trial over one or two cycles of chemotherapy. Data collection was based on observed response and patients' self-reporting. SETTING: Twenty Australian tertiary care hospitals in 1994. PATIENTS: 102 male and female patients from 18 to 75 years with histologically confirmed malignancy receiving their first chemotherapy containing > or = 50 mg/m2 cisplatin. INTERVENTION: In Cycle 1 tropisetron 5 mg was given intravenously before chemotherapy on Day 1, then 5 mg orally before breakfast on Days 2 to 6. In Cycle 2, dexamethasone 20 mg intravenously on Day 1, then 8 mg orally on Days 2 to 6 could be added to tropisetron if a complete antiemetic response had not been achieved in Cycle 1. MAIN OUTCOME MEASURES: Number of vomiting episodes and severity of nausea for 6 days after chemotherapy; severity of side effects; patient satisfaction with chemotherapy treatment; oestradiol levels in women; and past alcohol consumption in men and women. RESULTS: (i) The complete response rate (CR) for acute emesis in Cycle 1 was 64% (95% confidence interval [CI], 54%-72%), with 84% (95% CI, 76%-90%) having < or = 2 vomits. The CR for delayed emesis was 24% (95% CI, 17%-32%). The CR for acute nausea was 56% (95% CI, 47%-66%), with 97% (95% CI, 91%-99%) having < or = 2 nausea episodes. The CR for delayed nausea was 21% (95% CI, 14%-30%). Seventy-one patients received Cycle 2. The main side effects were headache (20 patients) and constipation (16 patients). The control of acute emesis was rated as "good" or "very good" by 68% of investigators; 85% rated the tolerability of treatment as "good" or "very good". Treatment was rated as "very satisfactory" or "satisfactory" by 52% of patients. (ii) The CR for acute emesis with dexamethasone added was 78% (95% CI, 64%-88%). (iii) Women with lower oestradiol levels had better control of emesis, although this difference was not statistically significant. Chronic alcohol intake and binge drinking were strongly associated with a complete acute antiemetic response. CONCLUSIONS: Tropisetron was effective for acute cisplatin-induced emesis; adding dexamethasone enhanced this response. Both single and combined therapy had less effect on delayed emesis. The impact of alcohol on control of emesis is a chronic rather than acute phenomenon which requires prospective testing.Ian N Olver, Paul S Craft, Phillip R Clingan, John H Kearsley, Robert S Planner, Guy A van Hazel, David R Bell, Michael R Adena, Barbara E Hall, Lesley L Pearsonhttp://www.ncbi.nlm.nih.gov/pubmed/860665

Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome.

In animal models, time-restricted feeding (TRF) can prevent and reverse aspects of metabolic diseases. Time-restricted eating (TRE) in human pilot studies reduces the risks of metabolic diseases in otherwise healthy individuals. However, patients with diagnosed metabolic syndrome often undergo pharmacotherapy, and it has never been tested whether TRE can act synergistically with pharmacotherapy in animal models or humans. In a single-arm, paired-sample trial, 19 participants with metabolic syndrome and a baseline mean daily eating window of ≥14 h, the majority of whom were on a statin and/or antihypertensive therapy, underwent 10 h of TRE (all dietary intake within a consistent self-selected 10 h window) for 12 weeks. We found this TRE intervention improves cardiometabolic health for patients with metabolic syndrome receiving standard medical care including high rates of statin and anti-hypertensive use. TRE is a potentially powerful lifestyle intervention that can be added to standard medical practice to treat metabolic syndrome. VIDEO ABSTRACT

Poverty and Transitions in Health

Using a sample of Europeans aged 50+ from twelve countries in the Survey of Health, Ageing and Retirement in Europe (SHARE) we analyse the role of poor material conditions as a determinant of changes in health over a four-year period. We find that poverty defined with respect to relative incomes has no effect on changes in health. However, broader measures of poor material conditions such as subjective poverty or low relative value of wealth significantly increase the probability of transition to poor health among the healthy and reduce the chance of recovery from poor health over the time interval analysed. In addition to this the subjective measure of poverty has a significant effect on mortality, increasing it by 40.3% among men and by 58.3% among those aged 50-64. Material conditions matter for health among older people. We suggest that if monitoring of poverty in old age and corresponding policy targets are to focus on the relevant measures, they should take into account broader definitions of poverty than those based only on relative incomes.Wir untersuchen den Einfluss materieller Umstände auf die Gesundheit der Bevölkerung 50+ in Europa. Dafür analysieren wir die Ergebnisse des Survey of Health, Ageing and Retirement in Europe (SHARE), einer repräsentativen Befragung von Personen im Alter 50+ aus 12 europäischen Ländern über einen Zeitraum von vier Jahren. Unsere Ergebnisse zeigen, dass das Leben in Armut, definiert über das relative Einkommen, keinen Einfluss auf die Gesundheit ausübt. Bei weiter gefassten Definitionen von Armut, wie der subjektiven Armut oder einem niedrigen relativen Vermögen, erhöht sich hingegen die Wahrscheinlichkeit, einen schlechteren Gesundheitszustand zu erreichen, die Genesungswahrscheinlichkeit im analysierten Zeitraum reduziert sich. Des Weiteren ergeben unsere Untersuchungen, dass das subjektive Armutsempfinden die Sterblichkeitsrate signifikant erhöht. Diese Wahrscheinlichkeit ist für Männer um 40,3 Prozent höher, bei den 50- bis 64-Jährigen sogar 58,3 Prozent höher. Solche Ergebnisse weisen darauf hin, dass die materiellen Lebensumstände entscheidend für die Gesundheit der älteren Generation sind. Wir empfehlen, dass sich die Messung von Armut innerhalb der älteren Generation sowie die Zielsetzung in der Politik auf weiter gefasste Armutsdefinitionen stützen sollte als lediglich über das Einkommen definierte

Outbreak of Influenza A (H3N2) Variant Virus Infection among Attendees of an Agricultural Fair, Pennsylvania, USA, 2011

During August 2011, influenza A (H3N2) variant [A(H3N2)v] virus infection developed in a child who attended an agricultural fair in Pennsylvania, USA; the virus resulted from reassortment of a swine influenza virus with influenza A(H1N1)pdm09. We interviewed fair attendees and conducted a retrospective cohort study among members of an agricultural club who attended the fair. Probable and confirmed cases of A(H3N2)v virus infection were defined by serology and genomic sequencing results, respectively. We identified 82 suspected, 4 probable, and 3 confirmed case-patients who attended the fair. Among 127 cohort study members, the risk for suspected case status increased as swine exposure increased from none (4%; referent) to visiting swine exhibits (8%; relative risk 2.1; 95% CI 0.2–53.4) to touching swine (16%; relative risk 4.4; 95% CI 0.8–116.3). Fairs may be venues for zoonotic transmission of viruses with epidemic potential; thus, health officials should investigate respiratory illness outbreaks associated with agricultural events