Twice‐weekly ixazomib in combination with lenalidomide‐dexamethasone in patients with newly diagnosed multiple myeloma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144661/1/bjh15394.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144661/2/bjh15394_am.pd

Human Rights Shaming Through INGOs and Foreign Aid Delivery

Does the ``shaming" of human rights violations influence foreign aid delivery decisions across OECD donor countries? We examine the effect of shaming, defined as targeted negative attention by human rights international nongovernmental organizations (INGOs), on donor decisions about how to deliver bilateral aid. We argue that INGO shaming of recipient countries leads donor governments, on average, to ``bypass" the recipient government in favor of non-state aid delivery channels, including international and local NGOs and international organizations (IOs). However, we expect this relationship to be conditional on a donor country's position in the international system. Minor power countries have limited influence in global affairs and are therefore more able to centrally promote human rights in their foreign policy. Major power countries, on the other hand, shape world politics and often confront ``realpolitik" concerns that may require government-to-government aid relations in the presence of INGO shaming. We expect aid officials of minor donor countries to be more likely to condition aid delivery decisions on human rights shaming than their counterparts of major donor countries. Using compositional data analysis, we test our argument using originally collected data on human rights shaming events in a time-series cross-sectional framework from 2004 to 2010. We find support for our hypotheses: On average, OECD donor governments increase the proportion of bypass when INGOs shame the recipient government. When differentiating between donor types we find that this finding holds for minor but not for major powers. These results add to both our understanding of the influences of aid allocation decision-making and our understanding of the role of INGOs on foreign-policy

MUC2 polymorphisms are associated with endometriosis development and infertility: a case-control study

<p>Abstract</p> <p>Background</p> <p>Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (<it>MUC2</it>) with the risk of endometriosis and endometriosis-related infertility.</p> <p>Methods</p> <p>This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) within <it>MUC2 </it>gene were performed by using <it>Taqman </it>genotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed by <it>χ</it>²test.</p> <p>Results</p> <p>Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (<it>P </it>= 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (<it>P </it>= 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs in <it>MUC2 </it>also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility.</p> <p>Conclusions</p> <p><it>MUC2 </it>polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women.</p

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

The Association Between Total Duration of Breastfeeding and Serum 25-Hydroxyvitamin D

BACKGROUND: Breastfed infants are at increased risk for developing vitamin D deficiency and rickets due to minimal vitamin D in breast milk. While previous research supports the association between exclusive breast-feeding and vitamin D deficiency, little is known about the effect of total duration of breastfeeding, which includes both the periods of exclusive breastfeeding and after the introduction of complementary foods, on vitamin D status. OBJECTIVES: To determine whether total duration of breastfeeding is associated with serum 25-hydroxyvitamin D (25-OHD) level in early childhood and to explore the effect of vitamin D supplementation on the relationship between total duration of breastfeeding and vitamin D status. DESIGN/METHODS: A cross-sectional study of healthy children seen for primary health care between September 2011 and August 2013 was conducted through the TARGet Kids! practice-based research network. Adjusted linear regression was used to determine the association between total duration of breastfeeding and serum 25-OHD and to explore the effect of vitamin D supplementation. Adjusted logistic regression was used to assess the probability of 25-OHD <20 ng/mL in supplemented vs. non-supplemented children. RESULTS: An association that was modified by vitamin D supplementation was identified between total duration of breastfeeding and serum 25-OHD (P=0.0251). Every one month increase in total duration of breastfeeding was associated with a 0.11 ng/mL lower median serum 25-OHD level (95% CI −0.20, −0.02 ng/mL) among children who were not supplemented. The odds of serum 25-OHD <20 ng/mL increased by 6% with every one month increase in total duration of breastfeeding among children who were not supplemented (OR=1.06, 95% CI 1.03, 1.10). There was no statistically significant association between total duration of breastfeeding and 25-OHD among children who did receive vitamin D supplementation (P=0.43). CONCLUSION: Breastfed children who do not receive vitamin D supplementation beyond the first year of life may be at an increased risk of inadequate vitamin D status. Vitamin D supplementation appears to mitigate this risk. These findings support the use of vitamin D supplementation during breastfeeding of any type and duration