Minor psychiatric disorders among Brazilian ragpickers: a cross-sectional study

BACKGROUND: Ragpickers are informal workers who collect recyclable materials to earn a small wage. Their life and working conditions are extremely difficult. We examined minor psychiatric disorders (MPD) among a cohort of ragpickers in Pelotas, a city in southern Brazil. METHODS: Ragpickers were matched by sex, age, and years of schooling with a sample of non-ragpickers from the same poor neighborhoods. The cross-sectional study gathered data by interview on 990 individuals in 2004. MPD were assessed using a standard self-reporting questionnaire, the SRQ-20. RESULTS: The prevalence of MPD among ragpickers was 44.7%, higher than reported by neighborhood controls (33.6%; p < 0.001). MPD were more common among females, those of lower economic level, smokers and alcoholics. Among occupational characteristics, MPD prevalence was associated with frequent static postures, low job satisfaction and recent work accidents. CONCLUSION: Ragpickers more frequently report MPD than other poor workers living in the same neighborhoods, with many of the same life conditions. Improving the work lives of these precarious workers should address not only the physical hazards of their jobs but their mental and emotional health as well

Alternative life-histories in a socially polymorphic ant

Social organisms vary greatly in the number of breeders per group; yet, the causes and consequences of this variation remain poorly known. Here, we show that variation in social structure is tightly linked with changes in several fundamental life-history traits within one population of ants. Multiple-queen colonies of Formica selysi were much more populous than single-queen ones. They also occurred in areas of higher nest density, had longer colony lifespan, produced smaller queens that presumably disperse less, and invested less in reproductive individuals relative to workers. These multiple changes in life histories are consistent with a shift in the mode of colony foundation and the degree of philopatry of queens. They may also provide various fitness benefits to members of multiple-queen colonies and are likely to play a central role in the evolution and maintenance of polymorphic social structures

The evolution of repeated mating under sexual conflict

In insects, repeated mating by females may have direct effects on female fecundity, fertility, and longevity. In addition, a female's remating rate affects her fitness through mortality costs of male harassment and ecological risks of mating such as predation. We analyse a model where these female fitness factors are put into their life-history context, and traded against each other, while accounting for limitations because of mate availability. We solve analytically for the condition when female multiple mating will evolve. We show that the probability that a female mates with a courting male decreases with increases in population density. The extent of conflict between the sexes thus automatically becomes larger at higher densities. However, because at higher densities females meet males at a higher rate, the resulting ESS female remating rate is independent of population density. The female remating probability is in conflict with male adaptations that increase male mating rate by persuading or forcing females to mate, and also in conflict with male adaptations for protecting the own sperm from being removed by future female mates. We show that the relative importance of these conflicts depends on population density

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study

Background: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. Methods: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2–3 vs &gt;3) and age (&lt;75 years vs ≥75 years). Treatments were assigned based on a permuted blocked randomisation scheme with a block size of four. The isatuximab–pomalidomide–dexamethasone group received isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, number NCT02990338. Findings: Between Jan 10, 2017, and Feb 2, 2018, we randomly assigned 307 patients to treatment: 154 to isatuximab–pomalidomide–dexamethasone, and 153 to pomalidomide–dexamethasone. At a median follow-up of 11·6 months (IQR 10·1–13·9), median progression-free survival was 11·5 months (95% CI 8·9–13·9) in the isatuximab–pomalidomide–dexamethasone group versus 6·5 months (4·5–8·3) in the pomalidomide–dexamethasone group; hazard ratio 0·596, 95% CI 0·44–0·81; p=0·001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab–pomalidomide–dexamethasone vs pomalidomide–dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab–pomalidomide–dexamethasone group and 14 (9%) in the pomalidomide–dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (&lt;1%) in the isatuximab–pomalidomide–dexamethasone group (sepsis) and two (1%) in the pomalidomide–dexamethasone group (pneumonia and urinary tract infection). Interpretation: The addition of isatuximab to pomalidomide–dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor. Funding: Sanofi. Video Abstract: [Figure presented] © 2019 Elsevier Lt

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study

Background: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. Methods: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged 6575 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2\u20133 vs &gt;3) and age (&lt;75 years vs 6575 years). Treatments were assigned based on a permuted blocked randomisation scheme with a block size of four. The isatuximab\u2013pomalidomide\u2013dexamethasone group received isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, number NCT02990338. Findings: Between Jan 10, 2017, and Feb 2, 2018, we randomly assigned 307 patients to treatment: 154 to isatuximab\u2013pomalidomide\u2013dexamethasone, and 153 to pomalidomide\u2013dexamethasone. At a median follow-up of 11\ub76 months (IQR 10\ub71\u201313\ub79), median progression-free survival was 11\ub75 months (95% CI 8\ub79\u201313\ub79) in the isatuximab\u2013pomalidomide\u2013dexamethasone group versus 6\ub75 months (4\ub75\u20138\ub73) in the pomalidomide\u2013dexamethasone group; hazard ratio 0\ub7596, 95% CI 0\ub744\u20130\ub781; p=0\ub7001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab\u2013pomalidomide\u2013dexamethasone vs pomalidomide\u2013dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab\u2013pomalidomide\u2013dexamethasone group and 14 (9%) in the pomalidomide\u2013dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (&lt;1%) in the isatuximab\u2013pomalidomide\u2013dexamethasone group (sepsis) and two (1%) in the pomalidomide\u2013dexamethasone group (pneumonia and urinary tract infection). Interpretation: The addition of isatuximab to pomalidomide\u2013dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor. Funding: Sanofi. Video Abstract: [Figure presented