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Background: New treatment options are needed for patients with multiple myeloma that is refractory to proteasome inhibitors and immunomodulatory drugs. We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma.Methods: In this open-label, multicentre, phase 2 trial done in Canada, Spain, and the USA, patients (age ≥18 years) with multiple myeloma who were previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or were refractory to both proteasome inhibitors and immunomodulatory drugs, were randomly allocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the study, to decide the dose for further assessment in part 2. Patients received 8 mg/kg every 4 weeks, or 16 mg/kg per week for 8 weeks (cycles 1 and 2), then every 2 weeks for 16 weeks (cycles 3-6), and then every 4 weeks thereafter (cycle 7 and higher). The allocation schedule was computer-generated and randomisation, with permuted blocks, was done centrally with an interactive web response system. In part 1 stage 2 and part 2, patients received 16 mg/kg dosed as in part 1 stage 1. The primary endpoint was overall response rate (partial response [PR] + very good PR + complete response [CR] + stringent CR). All patients who received at least one dose of daratumumab were included in the analysis. The trial is registered with ClinicalTrials.gov, number NCT01985126.Findings: The study is ongoing. In part 1 stage 1 of the study, 18 patients were randomly allocated to the 8 mg/kg group and 16 to the 16 mg/kg group. Findings are reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2. Patients received a median of five previous lines of therapy (range 2-14). 85 (80%) patients had previously received autologous stem cell transplantation, 101 (95%) were refractory to the most recent proteasome inhibitors and immunomodulatory drugs used, and 103 (97%) were refractory to the last line of therapy. Overall responses were noted in 31 patients (29.2%, 95% CI 20.8-38.9)-three (2.8%, 0.6-8.0) had a stringent CR, ten (9.4%, 4.6-16.7) had a very good PR, and 18 (17.0%, 10.4-25.5) had a PR. The median time to first response was 1.0 month (range 0.9-5.6). Median duration of response was 7.4 months (95% CI 5.5-not estimable) and progression-free survival was 3.7 months (95% CI 2.8-4.6). The 12-month overall survival was 64.8% (95% CI 51.2-75.5) and, at a subsequent cutoff, median overall survival was 17.5 months (95% CI 13.7-not estimable). Daratumumab was well tolerated; fatigue (42 [40%] patients) and anaemia (35 [33%]) of any grade were the most common adverse events. No drug-related adverse events led to treatment discontinuation.Interpretation: Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma, with a favourable safety profile in this population of patients.Funding: Janssen Research & Development. [ABSTRACT FROM AUTHOR]

Reports on learning and memory difficulties after environmental exposure to waterways in Maryland containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates. Methods of assessing the 24 people; Results showing people with high exposure were more likely than occupationally matched controls to complain of neuropsychological symptoms, including forgetfulness; Interpretation that exposure leads to risk of developing a reversible clinical syndrome of higher cognitive function difficulties.

Examines the impact of methamphetamine use on the risk for HIV/AIDS. Health complications associated with methamphetamine use, including hypertension, cardiomyopathy, and heart attack; Claim that methamphetamine use can increase high-risk sexual behaviors, and lead to an increased risk for sexually transmitted diseases; Incidence of methamphetamine use in the U.S.; View that an increased incidence of HIV among urban gay men can be traced to increased methamphetamine use; Discussion of the public perception of HIV and the potential for treatment; Potential methods of treatment for gay men engaged in methamphetamine and high-risk sexual behavior.

Presents an editorial on crime and age-appropriate punishment. Examination of the United States Supreme Court case, Roper v Simmons, which will determine if those committing crimes while under the age of 18 should be eligible for the death penalty; United States which is one of the last countries to condone killing minor criminals; Argument before the court which is based on the Eighth Amendment forbidding "cruel and unusual" punishment; Science which shows that the development of the adolescent brain does not fully mature until the early 20s; How development of the brain should result in a finding of limited mental capacity; Call for the United States Supreme Court to forbid the execution of teen criminals.

Presents an editorial on the catastrophic failures of public health as they manifest themselves in the inability to control obesity in developed countries. Background on early public health measures which eradicated many diseases; Figures from the Centers for Disease Control and Prevention which confirm that more than 60% of adult Americans are overweight or obese; Lack of a coordinated strategy for dealing with the issue which has tremendous health repercussions; Derk Wanless report for the UK government, "Securing Good Health for the Whole Population which attacks the short-term target culture; Belief that public health has become complacent and is failing; Suggestion of two approaches one of which includes turning cities and towns into safe places for pedestrians.

Reports research in the United States confirming that endogenous cannabinoids play a role in modulating reproductive behavior in rats. Details of molecular cross-talk between the three signalling systems of cannabinoids, neurotransmitter dopamine, and ovarian steroid hormones; Role of DELTA[sup9]-tetrahydrocannabinol (THC) and lordosis in the neurobiological process.

Reports that the United States Food and Drug Administration ruled that manufacturers of foods containing plant stanol and sterol esters can say that their products reduce the risk of heart disease. Publication of two papers which provided additional data on the effects of stanol and stanol esters; How sterol and stanol esters are similar to cholesterol and are thought to reduce serum LDL cholesterol values by interfering with cholesterol absorption in the gut.

Reports on how some diabetic patients drive automobiles even when their blood glucose levels are low. Study conducted at the University of Virginia Health Sciences Center; Percentage of participants who said they would drive when the blood glucose levels were low; Dangers involved in this decision.

Discusses research which concluded that exposure to the industrial contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the occurrence of all types of cancers, but only in very high doses. Research by Steenland et al at the United States National Institute for Occupational Safety and Health, Cincinnati, Ohio; Details and criticism of the research; Major source of TCDD being incineration.

Presents news from Lowell Hokin of the University of Wisconsin Medical School that Lithium effectively curbs extreme moods in patients with bipolar disorder by stabilising glutamate uptake in presynaptic nerve endings. Evidence Hokin has of the process.

Presents three brief articles related to medicine, as of March 7, 1998. Understanding how lithium helps in manic depression; Increased non-vigorous physical activity and higher insulin sensitivity; Epidemic of trampolining injuries to children in the United States.

Reports a study which showed that more than one-third of young children in the United States are exposed to environmental tobacco smoke (ETS), increasing their risk of respiratory disease. Study by the US National Health and Nutrition Examination Survey; Impact of ETS on chronic bronchitis, wheezing and asthma; Impact of prenatal maternal smoking; ETS having little effect on children aged three to five years.

Declares that American soldiers who served in Vietnam and later developed prostate cancer or peripheral neuropathy will be eligible for disability payments, as per the directive of President Bill Clinton. Plans to petition Congress for legislation providing benefits to veterans' children who have spina bifida; The ailments considered a result of American use of Agent Orange in Vietnam; The report issued by the US Institute of Medicine; Details of the plan.

Reports on cases involving adverse effects of and death due to inhalation of phosphine by illegal immigrants in railroad boxcars fumigated with aluminum phosphide. Lack of visible, non-English warning signs on the boxcars; Absence of uniform reporting.