Does gender affect environmentally virtuous behaviour? Evidence from selective waste collection.

This research analyses the issue, unexplored to date, of the causal relationship between women politicians and selective waste collection. Differing attitudes towards environmental issues between men and women may affect waste management at the municipal level, so an increase in women's political representation can be expected to enhance the effectiveness of selective waste collection. The analysis tests for this in Italy, exploiting a gender quota measure (Law 215/2012) as an exogenous shock to the percentage of female municipal councilors. Difference-in-differences instrumental variable analysis finds that an increase of one standard deviation in the percentage of female councilors increases the percentage of selective waste collection by 2.18 percentage points and the total tonnage of selective waste by 447.86. At the same time it reduces the amount of non-selective waste collection by 491.22 tonnes. The study comprises a number of sensitivity analyses for different model specifications, different definitions of dependent variables, different size of municipalities and different geographical areas.

Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma.

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.

Epstein-Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation.

Monitoring of Epstein-Barr virus (EBV) load and pre-emptive rituximab is an appropriate approach to prevent post-transplant lymphoproliferative disease (PTLD) occurring after hematopoietic stem cell transplantation (HSCT). This pre-emptive approach, based on EBV-DNA monitoring through a quantitative polymerase chain reaction, was applied to 101 consecutive patients who underwent allo HSCT at our Institute (median age 50). A single infusion of rituximab was administered to 11 of 16 patients who were at high risk for progression to PTLD, defined as a DNA value >10 000 copies/mL. All patients cleared EBV DNAemia, without any recurrences. Main factors significantly associated with high risk for PTLD were as follows: (i) unrelated vs. sibling (26% vs. 7%; p = 0.011); (ii) T-cell depletion (29% vs. 6%; p = 0.001); (iii) graft versus host disease (GVHD; 30% vs. 7%; p = 0.002); and (iv) cytomegalovirus (CMV) reactivation (29% vs. 4%; p = 0.001). Multivariate analysis showed that CMV reactivation was the only independent variable associated with EBV reactivation. We conclude that: (i) a single infusion of rituximab is able to prevent the risk of progression into EBV-related PTLD; and (ii) CMV reactivation is strongly associated with EBV reactivation; therefore, an intensive EBV monitoring strategy could be advisable only in case of CMV reactivation.

Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior.

Hairy cell leukemia (HCL) is generally responsive to single-agent cladribine, and only a minority of patients are refractory and with poor prognosis. HCLs generally express mutated (M) and, in a minority, unmutated (UM) IGHV. In a multicenter clinical trial in newly diagnosed HCL, we prospectively investigated clinical and molecular parameters predicting response and event-free survival after single-agent cladribine. Of 58 HCLs, 6 expressed UM-IGHV (UM-HCL) and 52 M-IGHV (M-HCL). Beneficial responses were obtained in 53 of 58 patients (91%), whereas treatment failures were observed in 5 of 58 patients (9%). Failures were associated significantly with UM-IGHV (5 of 5 failures vs 1 of 53 beneficial responses had UM-IGHV, P < .001), leukocytosis (3 of 5 vs 3 of 53, P = .006), and bulky spleen (4 of 5 vs 4 of 53, P < .001). The UM-HCL not benefiting from cladribine characteristically had bulky spleen (4 of 5, 80%), leukocytosis (3 of 5, 60%), and TP53 defects (2 of 5, 40%), and progressed rapidly after first treatment (median event-free survival, 7.5 months). Our data suggest that UM-HCLs identify the minor subgroup failing cladribine treatment and with more aggressive disease. High incidence of TP53 dysfunction indicates a potential mechanism of resistance to cladribine in the UM-HCL group. Overall, our data provide new molecular elements relevant for treatment concerns in HCL.

Osteonecrosis of the Jaw in Myeloma Patients Receiving Denosumab or Zoledronic Acid. A Commentary of the Pivotal Trial by Raje et al. Published on Lancet Oncology.

The recent randomized trial, published by Raje et al., on Lancet Oncology is potentially practice changing. It proposes that denosumab is a valid alternative to zoledronic acid in the treatment of myeloma patients. However, several points need further data and more details, such as information on incidence, diagnosis, and follow-up of osteonecrosis of the jaw (ONJ) cases, observed among treated patients. Adopted definition to adjudicate ONJ cases, type of registration of potential ONJ cases, length of observation are possible causes of potential underestimation of ONJ incidence in their study. Future updated evaluations with longer follow-up, and including actuarial estimation, are required for final judgment on ONJ risk in myeloma patients receiving denosumab, and comparison with ONJ risk by zoledronic acid.

Early mortality in myeloma patients treated with first-generation novel agents thalidomide, lenalidomide, bortezomib at diagnosis: A pooled analysis.

INTRODUCTION: Early toxic death (≤60 days of diagnosis) in elderly multiple myeloma (MM) patients is attributable to active disease, age and co-morbidities. Rate of early toxic deaths is 10% with conventional chemotherapy mainly due to infection and renal failure. Novel agents have improved MM outcome at the expense of newer toxicity. METHODS: We analyzed 1146 individual patient data to assess toxic deaths during induction treatment with first-generation novel agents thalidomide, lenalidomide, bortezomib. RESULTS: During first-line therapy, 119/1146 patients (10%) died for any cause, and 47/1146 (4%) due to toxicity, including 12/1146 (1%) early deaths. The 24-month cumulative incidence was 4.1% without any difference between bortezomib (18/503 patients, 4%) and lenalidomide (29/643patients, 5%; p = 0.31). Toxic deaths occurred in 34/1039 (3%) patients <80 years and 13/107 (12%) patients ≥80 years. Causes were cardiac events (28%), infections (26%) and vascular complications (15%). In a multivariate analysis, older age and unfavorable ISS stage increased the risk of death. CONCLUSION: First-generation novel agents significantly reduced toxic deaths compared to conventional chemotherapy. One third of deaths during first-line therapy were due to cumulative drug-related toxicities, thus supportive approaches and prevention strategies should be optimized. The higher mortality rate for toxicity in octogenarians confirms the need for a careful frailty assessment.

Prevention of bisphosphonates-induced osteonecrosis.

The osteonecrosis of the jaw is a new emergent disease, secondary to prolonged use of bisphosphonates. Bisphosphonates are a class of drug used in prevention and cure of bone diseases such as malignancy or bone metabolic diseases. In this article, we have tried to summarize, for patients taking IV or oral bisphosphonates-therapy, the most important informations on the pathogenesis and the risk factors in osteonecrosis of the jaw with particular attention about the preventive policies.

Osteonecrosis of the Jaws (ONJ) after Bisphosphonate Treatment in Patients with Multiple Myeloma: Decreasing ONJ Incidence after Adoption of Preventive Measures.

Bisphosphonates (BPs) are administered to Multiple Myeloma (MM) patients with bone lytic lesion. Osteonecrosis of the Jaw (ONJ) is a complication reported since 2003 in patients treated with intravenous (IV) BPs such as zoledronic acid and pamidronate, with 6%-26.3% frequency in early literature series, before some preventive measures were recommended. We evaluated the occurrence of ONJ with and without dental preventive measures in MM patients treated with BPs in our centre between 1996 and 2015. Since 2005, MM patients (already under treatment or before treatment) underwent a baseline mouth assessment (dental visit, Rx orthopantomography, and eventual tooth avulsion or dental care if necessary) and were followed by a multidisciplinary team. We reviewed the charts of 119 MM patients receiving IV BPs, classified into 3 groups: (a) "historic group" (21 patients who had started BP treatment in years before the awareness of ONJ); (b) "screening group" (20 patients starting BPs without baseline evaluation); and (c) "prevention group" (78 patients starting therapy only after baseline preventive assessment and eventual dental care measures). ONJ was observed in 3/21 patients (14.2%) from group a, in 2/20 patients (10%) from group b, and in no patients from group c (0%). Notably, the median number of IV BP administrations decreased after 2005. Our data confirmed a meaningful reduction of ONJ risk in MM patients treated with BPs if preventive measures are applied. Both implementation of prevention measures and reduction of cumulative doses of IV BPs could have contributed to a decreased incidence of ONJ.

Decreasing frequency of osteonecrosis of the jaw in cancer and myeloma patients treated with bisphosphonates: the experience of the oncology network of piedmont and aosta valley (north-Western Italy).

Background. Data concerning frequency of Osteonecrosis of Jaws (ONJ) are mostly based on single center experiences. Patients and Methods. Since 2005 a multidisciplinary study group collected data of cases of ONJ in patients treated with Bisphosphonates (BP) and observed in oncology and hematology centers of a regional network. Results. By December 2008, 221 cases were registered. We report details of 200 cases, identified after cross-checking reports from centres of medical oncology, haematology, and oral care. Primary neoplasm was breast cancer (39%), myeloma (32%), prostate cancer (16%), and other types of cancer (8%). In about 50% of the cases a history of dental extraction was present. Zoledronic acid was administered (alone or with other BP) to 178 patients (89%). Median time from first infusion to ONJ diagnosis was 21.0 (zoledronic acid only) and 39.0 months (pamidronate only). The number of ONJ cases per year was 3 in 2003, 21 in 2004, 58 in 2005, 60 in 2006, 37 in 2007, and 21 in 2008. Conclusion. The number of new ONJ cases in cancer and myeloma patients increased until 2006 and then reduced. The possible reasons of this trend (introduction of zoledronic acid; increase of ONJ awareness; diffusion of preventive dental measures; late modifications of BP prescription) are herein discussed.