Objective. To compare the efficacy and safety of mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IVC) as induction treatment for lupus nephritis (LN), by race, ethnicity and ...geographical region. Methods. A total of 370 patients with active Class III–V LN received MMF (target dose 3.0 g/day) or IVC (0.5–1.0 g/m2/month), plus tapered prednisone, for 24 weeks. Renal function, global disease activity, immunological complement (C3 and C4) and anti-dsDNA levels are the outcomes that were assessed in this study. Results. MMF was not superior to IVC as induction treatment (primary objective). There were important pre-specified interactions between treatment and race (P = 0.047) and treatment and region (P = 0.069) (primary endpoint). MMF and IVC response rates were similar for Asians (53.2 vs 63.9%; P = 0.24) and Whites (56.0 vs 54.2%; P = 0.83), but differed in the combined Other and Black group (60.4 vs 38.5%; P = 0.03). Fewer patients in the Black (40 vs 53.9%; P = 0.39) and Hispanic (38.8 vs 60.9%; P = 0.011) groups responded to IVC. Latin American patients had lower response to IVC (32 vs 60.7%; P = 0.003). Baseline disease characteristics were not predictive of response. The incidence of adverse events (AEs) was similar across groups. Serious AEs were slightly more prevalent among Asians. Conclusions. MMF and IVC have similar efficacy overall to short-term induction therapy for LN. However, race, ethnicity and geographical region may affect treatment response; more Black and Hispanic patients responded to MMF than IVC. As these factors are inter-related, it is difficult to draw firm conclusions about their importance. Trial registration. National Institutes of Health, www.clinicaltrials.gov, registration number NCT00377637.
The purpose of this study was to examine whether racial disparities exist in immediate postoperative pain scores and intraoperative analgesic regimens in a single surgical cohort.
A single-center, ...retrospective analysis.
This retrospective study of a single surgical cohort was conducted via chart review of the existing electronic health record. A total of 203 patients who underwent minimally invasive hysterectomy were included in the analysis. Three initially reviewed patient records were excluded from the final analysis due to the small size of their racial cohorts (two Asian or Pacific Islander and one Native American). The White patients (n = 103) and Black patients (n = 100) were compared for differences in pain scores in the postanesthesia care unit (PACU). The patients’ intraoperative analgesic regimens were also compared.
There were no significant differences between races in the postoperative pain scores in the PACU or in the analgesia administered by the anesthesia provider intraoperatively.
In this specific population, there was no evidence of racial disparities in postoperative pain or intraoperative analgesia administration. Further research is needed to understand the unique factors of the perioperative period, to see if the absence of disparities in this study is repeated in other cohorts, and to mitigate any disparities that are found.
Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus nephritis.
We carried out a ...36-month, randomized, double-blind, double-dummy, phase 3 study comparing oral mycophenolate mofetil (2 g per day) and oral azathioprine (2 mg per kilogram of body weight per day), plus placebo in each group, in patients who met response criteria during a 6-month induction trial. The study group underwent repeat randomization in a 1:1 ratio. Up to 10 mg of prednisone per day or its equivalent was permitted. The primary efficacy end point was the time to treatment failure, which was defined as death, end-stage renal disease, doubling of the serum creatinine level, renal flare, or rescue therapy for lupus nephritis. Secondary assessments included the time to the individual components of treatment failure and adverse events.
A total of 227 patients were randomly assigned to maintenance treatment (116 to mycophenolate mofetil and 111 to azathioprine). Mycophenolate mofetil was superior to azathioprine with respect to the primary end point, time to treatment failure (hazard ratio, 0.44; 95% confidence interval, 0.25 to 0.77; P = 0.003), and with respect to time to renal flare and time to rescue therapy (hazard ratio, <1.00; P < 0.05). Observed rates of treatment failure were 16.4% (19 of 116 patients) in the mycophenolate mofetil group and 32.4% (36 of 111) in the azathioprine group. Adverse events, most commonly minor infections and gastrointestinal disorders, occurred in more than 95% of the patients in both groups (P = 0.68). Serious adverse events occurred in 33.3% of patients in the azathioprine group and in 23.5% of those in the mycophenolate mofetil group (P = 0.11), and the rate of withdrawal due to adverse events was higher with azathioprine than with mycophenolate mofetil (39.6% vs. 25.2%, P = 0.02).
Mycophenolate mofetil was superior to azathioprine in maintaining a renal response to treatment and in preventing relapse in patients with lupus nephritis who had a response to induction therapy. (Funded by Vifor Pharma formerly Aspreva; ALMS ClinicalTrials.gov number, NCT00377637.).
We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans.
We ...coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion.
Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%-90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response.
Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649.
Cost studies of telehealth (TH) and virtual visits are few and report mixed results of the economic impact of virtual care and TH. Largely missing from the literature are studies that identify the ...cost of delivering TH versus in-person care. The objective was to demonstrate a modified time-driven activity-based costing (TDABC) approach to compare weighted labor cost of an in-person pediatric clinic sick visit before COVID-19 to the same virtual and in-person sick-visit during COVID-19.
We examined visits before and during COVID-19 using: (1) recorded structured interviews with providers; (2) iterative workflow mapping; (3) electronic health records time stamps for validation; (4) standard cost weights for wages; and (5) clinic CPT billing code mix for complexity weighs. We examined the variability in estimated time using a decision tree model and Monte Carlo simulations.
Workflow charts were created for the clinic before COVID-19 and during COVID-19. Using TDABC and simulations for varying time, the weighted cost of clinic labor for sick visit before COVID-19 was $54.47 versus $51.55 during COVID-19.
The estimated mean labor cost for care during the pandemic has not changed from the pre-COVID period; however, this lack of a difference is largely because of the increased use of TH.
: Our TDABC approach is feasible to use under virtual working conditions; requires minimal provider time for execution; and generates detailed cost estimates that have "face validity" with providers and are relevant for economic evaluation.
Individuals with chronic venous disease (CVeD) frequently experience associated leg pain that may influence disease management self-efficacy.
To evaluate the influence of a cooling intervention on ...leg pain associated with more severe stages of CVeD and self-efficacy. This was a secondary aim of the trial.
Randomized, blinded, comparator-controlled, multisite trial.
Three wound clinics and an academic medical research center in the United States of America.
276 participants (54.3% female, 46.7% male) with stage 4 and 5 CVeD were randomly assigned by computer generated tables to the cooling intervention group (n = 138) or control group (n = 138).
Participants received either a cooling (intervention) leg cuff or placebo cuff (control) to apply topically over the affected skin area. Both groups performed standard of care including wearing compression wraps and elevating legs for 30 min during the intervention. Study visits occurred at baseline, and months 1, 3, 6, and 9.
Visit measures included: Numeric Rating Scale (NRS) for short term pain; VEINES-QOL/Sym questionnaire for long-term pain; and, the Self Efficacy for Managing Chronic Disease Scale (SEMCD-6) for self-efficacy. Data were collected from September 2010 to December 2015 and analyzed using pooled t-tests, Chi-square tests, and mixed effects models. Observed 9-month patient retention rates were 94/138 (68.1%) in the intervention group and 91/138 (65.9%) in the control group. The primary analysis was based on the intention-to-treat principle.
Both the cooling intervention and control group experienced statistically significant decreases in unadjusted and adjusted mean NRS pain scores of 1.2 (95% CI: (−1.82, −0.64); p < 0.0001) and 1.8 (95% CI: (−2.31, −1.24); p < 0.0001) respectively from baseline, however, no statistically significant differences in change scores were observed between groups. The unadjusted mean VEINES-QOL/Sym pain scores had statistically significant decreases of 0.9 ((95% CI: (−1.07, −0.62) p < 0.0001 cooling)) and 0.8 (95% CI: (−1.09, −0.55) p < 0.0001 – control) points. When adjusting the scores for demographic and clinical features, both cooling and control groups maintained statistically significant decreases (p < 0.001 for both). No statistically significant differences in change scores were observed between groups. The unadjusted and adjusted mean self-efficacy scores had no statistically significant improvements from baseline to month 9 within and between the cooling and control groups.
Pain was reduced in both groups while self-efficacy did not change. Findings suggest that strictly implemented standard of CVeD care in each study group, with or without cooling, improved pain while there were no effects on self-efficacy.
Abstract Objective To evaluate the effectiveness of a community based participatory research (CBPR) developed, multi-level smoking cessation intervention among women in subsidized housing ...neighborhoods in the Southeastern US. Methods A total of n = 409 women in 14 subsidized housing neighborhoods in Georgia and South Carolina participated in this group randomized controlled trial conducted from 2009
to
2013. Intervention neighborhoods received a 24-week intervention with 1:1 community health worker contact, behavioral peer group sessions, and nicotine replacement. Control neighborhoods received written cessation materials at weeks 1, 6, 12, 18. Random coefficient models were used to compare smoking abstinence outcomes at 6 and 12 months. Significance was set a p < 0.05. Results The majority of participants (91.2%) were retained during the 12-month intervention period. Smoking abstinence rates at 12 months for intervention vs. control were 9% vs. 4.3%, p = 0.05. Additional analyses accounting for passive smoke exposure in these multi-unit housing settings demonstrated 12 month abstinence rates of 12% vs. 5.3%, p = 0.016. However, in the multivariate regression analyses, there was no significant effect of the intervention on the odds of being a non-smoker (OR = 0.44, 95
% CI: 0.18
–
1.07). Intervention participants who kept coach visits, attended group sessions, and used patches were more likely to remain abstinent. Conclusions This CBPR developed intervention showed potential to engage smokers and reduce smoking among women in these high-poverty neighborhoods. Effectiveness in promoting cessation in communities burdened with fiscal, environmental and social inequities remains a public health priority.
We examined whether electroconvulsive therapy (ECT) plus medications (“STABLE + PHARM” group) had superior HRQOL compared with medications alone (“PHARM” group) as continuation strategy after ...successful acute right unilateral ECT for major depressive disorder (MDD). We hypothesized that scores from the Medical Outcomes Study Short Form-36 (SF-36) would be higher during continuation treatment in the “STABLE + PHARM” group versus the “PHARM” group. The overall study design was called “Prolonging Remission in Depressed Elderly” (PRIDE). Remitters to the acute course of ECT were re-consented to enter a 6 month RCT of “STABLE + PHARM” versus “PHARM”. Measures of depressive symptoms and cognitive function were completed by blind raters; SF-36 measurements were patient self-report every 4 weeks.
Participants were 120 patients >60 years old. Patients with dementia, schizophrenia, bipolar disorder, or substance abuse were excluded. The “PHARM” group received venlafaxine and lithium. The “STABLE + PHARM” received the same medications, plus 4 weekly outpatient ECT sessions, with additional ECT session as needed. Participants were mostly female (61.7%) with a mean age of 70.5 ± 7.2 years. “STABLE + PHARM” patients received 4.5 ± 2.5 ECT sessions during Phase 2. “STABLE + PHARM” group had 7 point advantage (3.5–10.4, 95% CI) for Physical Component Score of SF-36 (P < 0.0001), and 8.2 point advantage (4.2–12.2, 95% CI) for Mental Component Score (P < 0.0001). Additional ECT resulted in overall net health benefit. Consideration should be given to administration of additional ECT to prevent relapse during the continuation phase of treatment of MDD.
NCT01028508
Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable.
We conducted a 24-week ...randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks.
Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate.
In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.
The purpose of this study was to examine the efficacy of a self-administered cooling treatment on clinically meaningful differences (CMDs) in symptom changes in patients with chronic venous disease.
...Blinded, prospective, randomized controlled trial.
Two hundred seventy-six community-dwelling adults 21 years and older with skin changes and/or a healed venous leg ulcer (Clinical-Etiologic-Anatomic-Pathologic CEAP 4 and 5 classification) completed the 6-month active treatment period.
Participants were recruited from wound and medicine clinics and from the general population through referrals or advertisements. Participants were randomly allocated to a sham control cuff or interventional cooling cuff group. Demographic and symptom-specific data were collected at baseline and at months 1, 3, and 6 with the 11-item symptom Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom (VEINES QOL/Sym) questionnaire subscale for heavy legs, aching legs, swelling, night cramps, heating or burning sensation, restless legs, throbbing, itching, tingling sensation (pins and needles), pain, and irritability. Participants in the intervention group received a cooling gel cuff and those in the control group received a cotton-filled cuff to be place around the most affected lower leg during leg elevation. Both groups received standard of care for their chronic venous disease with compression wraps and skin hygiene. Dosing consisted of daily 30-minute treatment for 1 month, twice weekly for 2 months, and then thrice weekly for 3 months. To analyze and compare data, a mixed percentage clinically meaningful percentage change was used to assess CMDs in symptoms between groups for treatment modality, sex, and age group.
All symptoms showed improvement, with throbbing, aching, itching, and pain demonstrating the greatest CMD in response to the cooling treatment. For throbbing and aching, similar improvements were noted in response to cooling; 50% in the cooling group showed improvement, whereas 60% in both groups responded favorably to pain. More than 50% of females and males reported improvements in throbbing; both males and females reported 60% improvements in pain in response to cooling. In contrast, far fewer females reported worsening of aching in the treatment group as compared to male participants (8% vs 20%). Age differences were noted for throbbing in the younger group (<65 years of age); older individuals 65 years or older saw CMDs in aching in response to cooling.
Of the 11 symptoms, aching, throbbing, itching, and pain had greater clinically meaningful improvements in response to a cooling cuff applied to lower leg skin affected by chronic venous disease. These CMDs inform evidence-based practice by enhancing clinician understanding of which symptoms, physical, physiological, and behavioral outcomes, respond to treatment change in a meaningful way for the patient.
PDF
