Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis.

OBJECTIVES: Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results. METHODS: We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC). RESULTS: Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset or =45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women. CONCLUSIONS: Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA

Welfare and Homelessness in Indianapolis: Populations at Risk and Barriers to Self-Sufficiency, Indianapolis

Who are the homeless in Indianapolis? How has welfare reform affected Indianapolis families who rely on public support? What barriers are preventing these populations from becoming self-sufficient? Two recent studies help answer these questions for policymakers and service providers. This issue brief summarizes the studies’ demographic findings, and the problems that erect barriers to self-sufficiency among the poor in Indianapolis

Validity, cut-points, and minimally important differences for two hot flash-related daily interference scales

OBJECTIVES: To conduct psychometric analyses to condense the Hot Flash-Related Daily Interference Scale (HFRDIS) into a shorter form termed the Hot Flash Interference (HFI) scale; evaluate cut-points for both scales; and establish minimally important differences (MIDs) for both scales. METHODS: We analyzed baseline and postrandomization patient-reported data pooled across three randomized trials aimed at reducing vasomotor symptoms (VMS) in 899 midlife women. Trials were conducted across five MsFLASH clinical sites between July 2009 and October 2012. We eliminated HFRDIS items based on experts' content validity ratings and confirmatory factor analysis, and evaluated cut-points and established MIDs by mapping HFRDIS and HFI to other measures. RESULTS: The three-item HFI (interference with sleep, mood, and concentration) demonstrated strong internal consistency (alphas of 0.830 and 0.856), showed good fit to the unidimensional "hot flash interference factor," and strong convergent validity with HFRDIS scores, diary VMS, and menopausal quality of life. For both scales, cut-points of mild (0-3.9), moderate (4-6.9), and severe (7-10) interference were associated with increasing diary VMS ratings, sleep, and anxiety. The average MID was 1.66 for the HFRDIS and 2.34 for the HFI. CONCLUSIONS: The HFI is a brief assessment of VMS interference and will be useful in busy clinics to standardize VMS assessment or in research studies where response burden may be an issue. The scale cut-points and MIDs should prove useful in targeting those most in need of treatment, monitoring treatment response, and interpreting existing and future research findings

MsFLASH Participants’ Priorities for Alleviating Menopausal Symptoms

Objective To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). Methods Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires. Results The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom. Conclusions Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and post-menopausal women. We used baseline data from 898 peri- and post-menopausal women recruited from multiple communities, ages 42–62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and post-menopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and post-menopausal women

Randomized, phase II selection study of ramucirumab and paclitaxel versus FOLFIRI in refractory small bowel adenocarcinoma: SWOG S1922

Background: Small bowel adenocarcinoma is a rare malignancy with limited evidence to support the choice of systemic chemotherapy beyond the frontline setting. Though second-line therapy has historically been extrapolated from colorectal cancers, recent molecular data has demonstrated small bowel adenocarcinoma to be genomically unique when compared to either colon or gastric cancer. Retrospective analyses of irinotecan- and taxane-based therapies and one prospective phase II clinical trial of nab-paclitaxel have demonstrated clinical activity in this cancer. Ramucirumab/paclitaxel represents an active combination in the management of gastric cancer. SWOG 1922 evaluates the use of FOLFIRI or ramucirumab/paclitaxel in the second- and later-line setting for small bowel adenocarcinoma. Methods: This is randomized, phase II, selection design clinical trial of FOLFIRI (5-fluorouracil, leucovorin and irinotecan) every two weeks or ramucirumab D1,15 and paclitaxel D1,8,15 every 4 weeks with the primary endpoint of progression-free survival (PFS). Secondary endpoints include response rate, overall survival, and safety. Archived paraffin tumor tissue collection and serial blood collections are included for correlative analyses. Key eligibility criteria include having mismatch repair proficient/microsatellite stable small bowel adenocarcinoma (ampullary location excluded); metastatic or locally advanced unresectable disease; prior fluoropyrimidine and/or oxaliplatin therapy; no prior treatment with irinotecan, ramucirumab, or taxanes; no recent bleeding, blood clots, or bowel perforation/fistula; and Zubrod performance status of 0/1. Measurable disease is not required. The null hypothesis is median PFS of 2.5 months. If a median PFS of at least 3.5 months is observed in one or both arms, the goal is to choose the better regimen with respect to this endpoint. The design provides a 90% probability of selecting the more active arm, assuming a hazard ratio of 1.4, if both arms meet this threshold. This trial is open and, as of September 1, 2021, 21 of 94 planned patients have been enrolled

Efficacy of yoga for vasomotor symptoms: a randomized controlled trial

OBJECTIVE: This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms (VMS) frequency and bother. METHODS: This study was a three-by-two factorial, randomized controlled trial. Eligible women were randomized to yoga (n = 107), exercise (n = 106), or usual activity (n = 142), and were simultaneously randomized to a double-blind comparison of ω-3 fatty acid (n = 177) or placebo (n = 178) capsules. Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice. Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline, 6 weeks, and 12 weeks. Secondary outcomes included insomnia symptoms (Insomnia Severity Index) at baseline and 12 weeks. RESULTS: Among 249 randomized women, 237 (95%) completed 12-week assessments. The mean baseline VMS frequency was 7.4 per day (95% CI, 6.6 to 8.1) in the yoga group and 8.0 per day (95% CI, 7.3 to 8.7) in the usual activity group. Intent-to-treat analyses included all participants with response data (n = 237). There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks (mean difference [yoga--usual activity] from baseline at 6 wk, -0.3 [95% CI, -1.1 to 0.5]; mean difference [yoga--usual activity] from baseline at 12 wk, -0.3 [95% CI, -1.2 to 0.6]; P = 0.119 across both time points). Results were similar for VMS bother. At week 12, yoga was associated with an improvement in insomnia symptoms (mean difference [yoga - usual activity] in the change in Insomnia Severity Index, 1.3 [95% CI, -2.5 to -0.1]; P = 0.007). CONCLUSIONS: Among healthy women, 12 weeks of yoga class plus home practice, compared with usual activity, do not improve VMS frequency or bother but reduce insomnia symptoms

Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518

Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs

Menopausal Quality of Life: A RCT of Yoga, Exercise and Omega-3 Supplements

Objective— Determine efficacy of three non-hormonal therapies for improving menopause- related quality of life (QOL) in women with vasomotor symptoms (VMS). Methods— 12-week 3×2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, ages 40-62 years, were randomized to yoga (n=107), exercise (n=106), or usual activity (n=142), and also randomized to double-blind comparison of omega-3 (n=177) or placebo (n=178) capsules. Interventions: 1) weekly 90-minute yoga classes with daily at-home practice; 2) individualized facility-based aerobic exercise training 3 times/week; and 3) 0.615 gram omega-3 supplement, 3 times/day. Outcomes: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (VMS, psychosocial, physical and sexual) scores. Results— Among 355 randomized women, average age 54.7 years, 338 (95%) completed 12- week assessments. Mean baseline VMS frequency was 7.6/day and mean baseline total MENQOL score was 3.8 (range 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% CI -0.6 to 0.0, p=0.02), and VMS (p=0.02) and sexuality (p=0.03) domain scores. For exercise and omega-3 compared to controls, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12- weeks (p=0.02). Conclusion— All women become menopausal and many seek medical advice on ways to improve quality of life; little evidence-based information exists. We found, among healthy sedentary menopausal women, yoga appears to improve menopausal QOL - the clinical significance of our finding is uncertain due to modest effect

Peripheral Blood Hematopoietic Stem Cells for Transplantation of Hematological Diseases from Related, Haploidentical Donors after Reduced-Intensity Conditioning

AbstractIn a multicenter collaboration, we carried out T cell–replete, peripheral blood stem cell (PBSC) transplantations from related, HLA-haploidentical donors with reduced-intensity conditioning (RIC) and post-transplantation cyclophosphamide (Cy) as graft-versus-host disease (GVHD) prophylaxis in 55 patients with high-risk hematologic disorders. Patients received 2 doses of Cy 50 mg/kg i.v. on days 3 and 4 after infusion of PBSC (mean, 6.4 × 106/kg CD34+ cells; mean, 2.0 × 108/kg CD3+ cells). The median times to neutrophil (500/μL) and platelet (>20,000/μL) recovery were 17 and 21 days respectively. All but 2 of the patients achieved full engraftment. The 1-year cumulative incidences of grade II and grade III acute GVHD were 53% and 8%, respectively. There were no cases of grade IV GVHD. The 2-year cumulative incidence of chronic GHVD was 18%. With a median follow-up of 509 days, overall survival and event-free survival at 2 years were 48% and 51%, respectively. The 2-year cumulative incidences of nonrelapse mortality and relapse were 23% and 28%, respectively. Our results suggest that PBSC can be substituted safely and effectively for bone marrow as the graft source for haploidentical transplantation after RIC