Difference In Mean Change Research Articles

Phosphorus balance calculator: an individualized tool for treatment of hyperphosphatemia in hemodialysis patients.

Lack of evaluations of the dietary phosphorus and dialysis phosphorus removal in daily clinical practice are common obstacles to assessing phosphorus balance and controlling phosphorus in hemodialysis patients. We aimed to investigate whether individualized therapy using a phosphorus balance calculator improves phosphorus control. A randomized, open-label, multicenter, 4-week clinical trial was conducted. A total of 119 maintenance hemodialysis patients aged 18-85years old and with serum phosphorus level >1.45mmol/L from three university teaching hospitals in Shanghai were enrolled. Patients were randomized in a 1:1 ratio to individualized therapy (n=60) or conventional therapy (n=59). The primary outcome was the serum phosphorus concentration after 4-week treatment. Secondary outcomes included the serum calcium and parathyroid hormone (PTH) concentrations, changes in serum phosphorus, calcium and PTH concentrations, and the proportion of patients achieving target ranges of serum phosphorus, calcium and PTH after 4-week treatment. Among 119 randomized participants [mean age 62years; 68 male (57%)], 116 completed the trial. Using the phosphorus balance calculator, the individualized group achieved a better phosphorus balance state and significantly reduced serum phosphorus (1.62±0.45mmol/L versus 1.85±0.45mmol/L, P=.006), increased the proportions of patients achieving target serum phosphorus range (41% versus 18%, P=.006) and had greater adjusted mean difference in change in serum phosphorus over the 4weeks (-0.47 versus -0.23mmol/L, P=.010) when compared with conventional therapy. No significant changes were observed in serum calcium and PTH levels, the proportion of patients achieving target serum calcium or PTH levels, or the adjusted mean difference of serum calcium and PTH levels over the treatment period. Phosphorus balance calculator was proved to improve serum phosphorus control in patients undergoing maintenance hemodialysis, offering a new tool for managing hyperphosphatemia.

Plasma Exchange versus Intravenous Immunoglobulin in Worsening Myasthenia Gravis: A Systematic Review and Meta-Analysis with Special Attention to Faster Relapse Control.

Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was -2.8 (95% CI: -5.614-0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25-4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.

Sodium glucose co-transporter 2 inhibitors and quality of life in patients with heart failure: a comprehensive systematic review and meta-analysis of randomized controlled trials.

Sodium glucose co-transporter 2 inhibitors (SGLT2i) are one of the cornerstones of heart failure (HF) therapy. While benefits in terms of HF hospitalizations and death are well established, their impact on quality-of-life (QoL) has not been systematically investigated. This systematic review and meta-analysis aims to evaluate the impact of SGLT2i treatment on QoL in patients with HF, by analysing data from randomized clinical trials (RCTs). We identified a total of 23 RCTs that investigated the role of SGLT2i on quality of life in patients with HF, irrespective of their left ventricular ejection fraction (LVEF). RCTs that used Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) to assess QoL and had a minimum follow-up of 3 months were included. The difference in mean change of the KCCQ-OSS between the SGLT2i group and the standard of care (SOC) group at 3 and 6 months from baseline was considered as the outcome measure. Fourteen RCTs (21737 patients) were included in the analysis. A significant improvement in KCCQ-OSS over time (p<0.001) was observed in both patients receiving SOC and those receiving SGLT2i in addition. The pooled estimate showed a significant improvement of 1.94 points [95% confidence interval (CI), 1.41-2.46] in KCCQ-OSS mean change at 3 months and of 2.18 points (95% CI, 1.13-3.24) at 6 months from baseline, with SGLT2i compared to SOC alone, irrespective of LVEF. A greater improvement in KCCQ-OSS was observed among patients with a recent episode of worsening HF compared to those with chronic stable HF. Among patients with HF, irrespective of their LVEF and clinical status, the addition of SGLT2i to SOC demonstrated a significant improvement in quality of life as early as at 3-month follow-up.

Comparison of virtual vs face-to-face medical nutrition therapy in patients with hyperlipidemia

Since the COVID-19 pandemic, utilization of telemedicine visits has increased. The outcomes of virtual compared to face-to-face (F2F) visits for treating hyperlipidemia are uncharacterized. This observational study compared pre- to post-visit change in lipid markers between 41 virtual and 151 F2F visits with a registered dietitian nutritionist at the University of Michigan Preventive Cardiology program from 3/31/2019–9/31/2022. Total cholesterol (TC), high-density lipoprotein (HDL), and triglycerides (TG) were collected pre- and post-visit with a median 33 days between collections. Low-density lipoprotein (LDL-C) was calculated using the Sampson equation. We used paired T-tests to evaluate mean change in lipid markers for each visit type between pre and post timepoints, and linear regression to compare virtual to F2F visits. There was a significant decrease in TC, LDL-C, and non-HDL-C for both visit types. There was no significant difference in mean change in lipid markers between virtual and F2F visits. Telehealth is a promising strategy for increasing access to medical nutrition therapy.

Impact of a Pharmacist-Managed Telemedicine Pharmacotherapy Clinic in the Era of COVID-19

Purpose: Telemedicine has been essential during the coronavirus disease 2019 (COVID-19) pandemic. In March 2020, pharmacist-led chronic disease state management services at our family care centers and primary care clinics were converted to telemedicine. This study aimed to determine the impact of expanding telemedicine services on appointment adherence, clinical outcomes, and financial reimbursement. Methods: This was a single-center, retrospective, quasi-experimental study of the impact of expanding telemedicine services on adult patients with diabetes, hypertension, and/or hyperlipidemia. The study included patients scheduled with a pharmacist at a hospital-based (HB) or physician-based (PB) clinic. The primary outcome was the difference in the mean no-show rate. The secondary outcomes were differences in mean change in HbA1c, LDL, blood pressure, and reimbursement. Mean differences between pre- and post-telemedicine groups of each clinic were measured for all outcomes. Results: The mean difference (SE) in the no-show rate in the HB clinic was -12.09% (4.862; P = .014), compared to 2.88% (3.656; P = .431) in the PB clinic. The mean difference (SE) in the change in HbA1c in the HB clinic was .00% (.338; P = .992), compared to .01% (.239; P = .945) in the PB clinic. The mean difference (SE) in reimbursement in the HB clinic was $1.93 (4.209; P = .647), compared to $20.46 (3.210; P < .0001) in the PB clinic. Conclusion: Expansion of pharmacy telemedicine services provided evidence for improved appointment adherence in the HB clinic and increased reimbursement in the PB clinic. No change in healthcare outcomes was observed.

Local anesthesia during S-ICD implantation gives similar post procedural pain perception as sedation

Abstract Introduction The PRAETORIAN-DFT trial hypothesises that subcutaneous implantable cardioverter defibrillator (S-ICD) implant without defibrillation test (DFT) but with PRAETORIAN score is non-inferior to S-ICD implant with DFT with regard to first shock efficacy in spontaneous events. Various anesthesia protocols are used for S-ICD implant, ranging from local to general anesthesia. Sedation of the patient during S-ICD implantation is required because of DFT. Without the need for DFT, local anesthesia may suffice, thereby reducing the logistical burden associated with sedation and general anesthesia. However, data comparing the effects of various anesthesia methods are lacking. Purpose This prespecified analysis of the PRAETORIAN-DFT trial aims to investigate the effect of three different anesthesia methods on (post-)operative pain during S-ICD implant. Methods In the PRAETORIAN-DFT trial (NCT03495297), 965 patients were randomised to DFT (N=483) or no DFT with PRAETORIAN Score calculation (N=482). Choice of anesthesia protocol was per local routine and physician discretion and was listed as local anesthesia (LA), monitored anesthesia care (MAC) or general anesthesia (GA). Patients under LA who underwent DFT, had MAC or GA during the test. Pain scores were assessed using the Numerical Rating Scale (NRS), prior to implant (baseline) and at 1-3 hours, 5-7 hours and 1 day post implant. Mean change in NRS compared to baseline was calculated at every time point. Exact pain scores as well as mean change in NRS were compared between anesthesia methods using a Kruskal Wallis Test. Results Pre-implant pain questionnaires were completed by 97% of patients. In the complete study cohort, 149/965 (15%) of implants were performed under LA, 327/965 (34%) under MAC and 489/965 (51%) under GA. This distribution did not differ between the randomised arms (p=0.301). There was no difference in NRS or mean change compared to baseline between the groups at any time post implant. The mean change in NRS compared to baseline was highest at 5-7 hours post implant in all groups (Figure). Analysis with patients under LA and MAC or GA during DFT as independent group showed similar results. Conclusion There was no difference in pain perception after S-ICD implantation between implant under local anesthesia, MAC and general anesthesia. These results confirm that S-ICD implantation under local anesthesia is feasible and sedation may be no longer necessary if defibrillation testing becomes redundant.Mean changes in NRS compared to baseline

MIROC6 Large Ensemble (MIROC6-LE): experimental design and initial analyses

Abstract. Single model initial-condition large ensembles (LEs) are a useful approach to understand the roles of forced responses and internal variability in historical and future climate change. Here, we produce one of the largest ensembles thus far using the MIROC6 coupled atmosphere–ocean global climate model (MIROC6-LE). The total experimental period of MIROC6-LE is longer than 76 000 years. MIROC6-LE consists of a long preindustrial control run, 50-member historical simulations, 8 single forcing historical experiments with 10 or 50 members, 5 future scenario experiments with 50 members and 3 single forcing future experiments with 50 members. Here, we describe the experimental design. The output data of most of the experiments are freely available to the public. This dataset would be useful to a wide range of research communities. We also demonstrate some examples of initial analyses. Specifically, we confirm that the linear additivity of the forcing-response relationship holds for the 1850–2020 trends of the annual mean values and extreme indices of surface air temperature and precipitation by analyzing historical fully forced runs and the sum of single forced historical runs. To isolate historical anthropogenic signals of annual mean and extreme temperature for 2000–2020 relative to 1850–1900, ensemble sizes of 4 and 15, respectively, are sufficient in most of the world. Historical anthropogenic signals of annual mean and extreme precipitation are significant with the 50-member ensembles in 76 % and 69 % of the world, respectively. Fourteen members are sufficient to examine differences in changes in annual mean values and extreme indices of temperature and precipitation between the shared socioeconomic pathways (ssp), ssp585 and ssp126, in most of the world. Ensembles larger than 50 members are desirable for investigations of differences in annual mean and extreme precipitation changes between ssp126 and ssp119. Historical and future changes in internal variability, represented by departures from the ensemble mean, are analyzed with a focus on the El Niño/Southern Oscillation (ENSO) and global annual mean temperature and precipitation. An ensemble size of 31 is large enough to detect ENSO intensification from preindustrial conditions to 1951–2000, from 1951–2000 to 2051–2100 in all future experiments, and from low- to high-emission future scenario experiments. The single forcing historical experiments with 27 members can isolate ENSO intensification due to anthropogenic greenhouse gas and aerosol forcings. Future changes in the global mean temperature variability are discernible with 23 members under all future experiments, while 50 members are not sufficient for detecting changes in the global mean precipitation variability in ssp119 and ssp126. We also confirm that these temperature and precipitation variabilities are not precisely analyzed when detrended anomalies from the long-term averages are used due to interannual climate responses to the historical natural forcing, which highlights the importance of large ensembles for assessing internal variability.

Factor B Inhibition with Oral Iptacopan Monotherapy Demonstrates Sustained Long-Term Efficacy and Safety in Anti-C5-Treated Patients (pts) with Paroxysmal Nocturnal Hemoglobinuria (PNH) and Persistent Anemia: Final 48-Week Results from the Multicenter, Phase III APPLY-PNH Trial

Drs Roeth and Kulasekararaj contributed equally as authors. Background: Iptacopan is the first oral complement inhibitor that acts proximally in the complement system to target factor B in the alternative pathway. Iptacopan has shown efficacy/safety in PNH pts with persistent anemia despite anti-C5 therapy and complement inhibitor-naive pts. In the Phase III APPLY-PNH trial (NCT04558918), iptacopan monotherapy led to clinically meaningful hemoglobin (Hb) increases and normal/near-normal Hb levels in a majority of pts, transfusion avoidance and improved pt-reported fatigue, showing superiority vs C5 inhibitors at Week (Wk) 24. Aim: We report the final APPLY-PNH data after a 24-wk extension period in which all pts received iptacopan monotherapy (study completion: 6 March 2023). Methods: Adult PNH pts (mean Hb &amp;lt;10 g/dL, receiving anti-C5 therapy for ≥6 months) were randomized to receive iptacopan 200 mg twice daily or continue their anti-C5 regimen for 24 wks. Pts could then opt to enter an extension period; pts in the iptacopan arm received iptacopan for another 24 wks and pts who had been receiving anti-C5 switched to iptacopan monotherapy. Results: In the extension period, 95 pts received iptacopan: 61/62 in the iptacopan arm (1 discontinued iptacopan in the randomized period because of pregnancy) and 34/35 in the anti-C5-to-iptacopan arm (1 did not enter the extension period [investigator's decision]). In the iptacopan arm, the improvements at 24 wks were sustained at 48 wks, with maintenance of increased Hb, normal/near-normal mean Hb levels (Figure), improved Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) scores, decreased absolute reticulocyte counts (ARCs) and transfusion avoidance (Table). Pts who switched from anti-C5 to iptacopan had rapid changes in Hb, FACIT-F and ARC, achieving comparable improvements to the iptacopan arm. Mean Hb levels at Wk 48 were 12.2 and 12.1 g/dL in the iptacopan and anti-C5-to-iptacopan arms, respectively (standard deviations 1.6 and 1.4). At Wk 48, the adjusted mean change from baseline in the iptacopan arm was +3.35 g/dL for Hb, +9.80 FACIT-F points and −106.26 × 10 9/L for ARC. In the anti-C5-to-iptacopan arm, the adjusted mean change from baseline at Wk 48 was +3.36 g/dL for Hb, +10.96 FACIT-F points and −107.95 × 10 9/L for ARC (adjusted mean difference in change from baseline at Wk 48 vs Wk 24: +3.02 g/dL, +10.79 points and −102.29 × 10 9/L, respectively). Transfusion avoidance was achieved by 93.5% of pts in the iptacopan arm (Wks 2 to 48) and 94.1% in the anti-C5-to-iptacopan arm (Wks 26 to 48). Mean lactate dehydrogenase levels were generally maintained &amp;lt;1.5 × upper limit of normal in both arms. In the trial, 6/62 pts in the iptacopan arm had clinical breakthrough hemolysis (BTH). One pt in the anti-C5-to-iptacopan arm had clinical BTH after switching to iptacopan. BTH resolved without changing iptacopan dosing. Three pts had major adverse vascular events (MAVEs; randomized period: 1 serious transient ischemic attack [TIA]; extension period: 1 non-serious TIA, 1 serious portal vein thrombosis [PVT]). The pt with PVT had a history of PVT and discontinued heparin prior to the MAVE. All MAVEs were considered unrelated to iptacopan and resolved without changing iptacopan dosing. After 48 wks in the iptacopan arm, the most frequently reported treatment-emergent adverse events (TEAEs) were COVID-19 (29.0% of pts), headache (19.4%), diarrhea (16.1%) and nasopharyngitis (14.5%). There were no deaths, no serious hemolysis TEAEs on iptacopan, no serious infections caused by N. meningitidis, S. pneumoniae or H. influenzae and no pts discontinued treatment because of TEAEs. Conclusions: Long-term data from the Phase III APPLY-PNH trial show a durable response to iptacopan monotherapy in anti-C5-treated PNH pts with persistent anemia. Pts who received iptacopan for 48 wks had sustained improvements in multiple hematological and clinical outcomes, including maintenance of increased Hb, mean normal/near-normal Hb levels, transfusion avoidance and decreased pt-reported fatigue; these benefits quickly emerged in the anti-C5-to-iptacopan arm, supporting the benefit of switching from C5 inhibitors to iptacopan monotherapy. The data indicate good control of hemolysis by iptacopan and a similar safety profile at Wk 48 vs Wk 24. Our findings continue to support oral iptacopan monotherapy as a potentially practice-changing treatment for hemolytic PNH.

Effects of Idecabtagene Vicleucel (Ide-Cel) Versus Standard Regimens on Health-Related Quality of Life (HRQoL) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Had Received 2-4 Prior Regimens: Updated Results from the Phase 3 KarMMa-3 Trial

Background: An interim analysis (data cutoff date April 18, 2022) of the international, open-label, phase 3 KarMMa-3 trial (NCT03651128) showed the chimeric antigen receptor T cell therapy idecabtagene vicleucel (ide-cel) significantly improved progression-free survival and treatment response rates, as well as HRQoL, as compared with standard regimens, in patients with triple-class exposed (TCE) RRMM who had received 2-4 prior regimens (Rodriguez-Otero P, et al. N Engl J Med 2023;388:1002-1014; Delforge M, et al., HemaSphere, 2023;7(S3):P905). The aim of the present study was to analyze the effect of ide-cel versus standard regimens (daratumumab [DARA], pomalidomide, and dexamethasone [DEX]; DARA, bortezomib, and DEX; ixazomib, lenalidomide, and DEX; carfilzomib and DEX; or elotuzumab, pomalidomide, and DEX) on HRQoL in KarMMa-3 trial participants with an extended follow-up of patient-reported outcomes (PRO) data collection (data cutoff date April 28, 2023). Methods: In KarMMa-3, HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30), EORTC Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20), and EQ-5D-5L. HRQoL assessments were completed at screening (baseline); the day of ide-cel infusion or the first dose of standard treatment; and monthly from 2 to 28 months; and every 3 months thereafter. The prespecified primary outcomes of interest were EORTC QLQ-C30 global health status/QoL, physical functioning, cognitive functioning, fatigue, and pain; EORTC QLQ-MY20 disease symptoms and side effects of treatment; and the EQ-5D visual analog scale (EQ-VAS). Least squares (LS) mean changes from baseline through month 25 for ide-cel and standard regimens were compared by constrained longitudinal data analysis (cLDA). Effect sizes were estimated by Hedges' g. The effect of ide-cel versus standard regimens on time to confirmed improvement and deterioration in HRQoL (defined by prespecified change thresholds and sustained duration) were compared by stratified Cox proportional hazards regression. There was no adjustment for multiple testing, and all P values reported are nominal. Results: Overall, 254 patients were randomized to the ide-cel arm and 132 to the standard regimens arm. Baseline characteristics were well balanced across treatment arms; both arms had a median age of 63 years, a median of 3 prior anti-myeloma regimens, and median time from MM diagnosis to screening was 4 years. The baseline HRQoL scores were generally comparable between treatment arms. Overall LS mean changes from baseline to month 25 showed significant differences (nominal P value &amp;lt; 0.05) in favor of ide-cel for 18 out of 21 HRQoL domains, with effect sizes (Hedges' g) of 0.27 to 0.82 (Table). For 13 of these domains (including 6 primary domains of interest), the difference in overall LS mean change from baseline exceeded the prespecified minimum important difference (MID) threshold. Time to confirmed improvement was significantly shorter in the ide-cel arm than the standard regimens arm for 19 domains, including all primary domains of interest (Table). Time to confirmed deterioration showed trends of being longer in the ide-cel arm than the standard regimens arm for most domains and was significantly longer for emotional functioning, cognitive functioning, social functioning, dyspnea, and constipation as measured by the EORTC QLQ-C30. The time to confirmed deterioration in side effects of treatment (based on the EORTC QLQ-MY20) was significantly longer for patients in the ide-cel arm and time to confirmed improvement was significantly faster, as compared with the standard regimens arm (Table). Conclusions: In the KarMMa-3 trial, patients with TCE RRMM who had received 2-4 prior regimens, ide-cel significantly and meaningfully improved MM-relevant symptoms, functioning, and overall health status/HRQoL compared with standard regimens. Confirmed HRQoL improvements in the ide-cel arm occurred sooner than standard regimens. PRO improvements were sustained over more than 2 years, which is notable after a single infusion treatment with ide-cel. These patient-reported findings further support the benefit of ide-cel in this patient population.

Durable Symptom Improvement for Patients with Non-Transfusion Dependent Thalassemia Treated with Luspatercept: Patient-Reported Outcomes from the BEYOND Study

Background: Patients with non-transfusion dependent beta-thalassemia (NTDT) suffer from chronic anemia due to ineffective erythropoiesis. The phase 2, randomized, placebo-controlled BEYOND study demonstrated that luspatercept increased hemoglobin (Hb), reduced transfusion burden, and improved NTDT-related symptoms based on the data with 48 weeks of follow-up (Taher A, et al. Lancet Haematol. 2022;9(10):E733). Objective: The purpose of this analysis was to investigate the long-term effect of luspatercept + best supportive care (BSC) vs placebo + BSC on NTDT-related symptoms through 96 weeks using data collected in the BEYOND study. Methods: 145 patients with NTDT were randomized 2:1 to luspatercept (Q3W) + BSC or placebo + BSC. BSC included red blood cell (RBC) transfusions and iron chelation therapy as deemed necessary by investigators. Patients completed the NTDT Patient Reported Outcome (NTDT-PRO) and Patient Global Impression of Severity (PGI-S) in a daily electronic diary starting 7 days prior to the first dosing day until Week 24, and thereafter over the 7 days prior to dosing at every other dosing visit. The Patient Global Impression of Change (PGI-C) was administered at every other dosing visit, starting with the first dosing day. The NTDT-PRO consists of 6 questions measuring 2 NTDT anemia-related symptom domains: Tiredness/Weakness (T/W) and Shortness of Breath (SoB), each with a score range of 0 (no symptoms) to 10 (extreme symptoms). The PGI-S asks patients to rate the overall severity of their NTDT-related symptoms (range of 0 to 10, with a higher score indicating greater severity), whereas the PGI-C asks patients to rate the overall change in their NTDT-related symptoms since the start of the study (7-level verbal rating scale ranging from “a great deal better” to “a great deal worse”). Least squares (LS) mean changes from baseline at each visit (up to Week 96) in NTDT-PRO T/W and SoB scores, as well as the PGI-S score, were estimated using a mixed model for repeated measures (MMRM). Responses to the PGI-C were descriptively summarized by treatment group. All analyses were performed in the health-related quality of life (HRQoL)-evaluable population, defined as all randomized patients with a valid QoL assessment and at least 1 post-baseline assessment. All p-values reported from the analyses were nominal. Results: The HRQoL-evaluable population consisted of 95 of the 96 patients randomized to the luspatercept arm and all 49 patients randomized to the placebo arm. LS mean changes from baseline in both the NTDT-PRO T/W and SoB scores for the luspatercept arm consistently demonstrated greater improvement (i.e., lower scores) than the placebo arm across visits. Improvement in both T/W and SoB domains were more pronounced starting at Week 24 and sustained through Week 96, with differences in LS mean changes from baseline ranging from -0.89 to -0.21 in the T/W domain and from -0.80 to -0.45 in the SoB domain over this time period (both domains on a 0 to 10 scale). Between-treatment differences were significant (p&amp;lt;0.05) at Week 30 (between-treatment difference in LS mean change from baseline, 95% confidence interval: -0.76, -1.42 to -0.10), Week 36 (-0.89, -1.55 to -0.22), and Week 72 (-0.81, -1.54 to -0.09) in the T/W domain and at Week 30 (-0.71, -1.36 to -0.06), Week 48 (-0.77, -1.43 to -0.10), and Week 72 (-0.80, -1.51 to -0.10) in the SoB domain. LS mean changes from baseline in the severity of overall NTDT-related symptoms, assessed by the PGI-S, showed a marked improvement through Week 96 in the luspatercept arm ( Figure 1), whereas patients receiving placebo tended to worsen over time. The between-treatment difference was statistically significant (p&amp;lt;0.05) across most assessment visits from Weeks 18 to 96. For the PGI-C, most patients treated with luspatercept reported “a little better” or more on their overall NTDT-related symptoms at Weeks 72 (89%) and 96 (87%), whereas most patients receiving placebo reported no change at either Week 72 (61%) or 96 (75%) ( Figure 2). Conclusions: Analysis of the PRO data collected in BEYOND suggests that, in addition to improvements in Hb, patients with NTDT treated with luspatercept experienced durable improvement in NTDT-related symptoms, from a patient perspective, through at least 96 weeks of treatment.

Effect of the weight-loss program using daily self-weighing combined with personalized counseling led by village health volunteers in adults with obesity in a rural community, Thailand: a randomized controlled trial

BackgroundIn a remote rural community in central Thailand, obesity prevalence among adults significantly rose from 33.9% in 2012 to 44.8% in 2018. Limited information on weight reduction studies in Thai rural communities was available. The present study aims to evaluate the effect of daily self-weighing combined with personalized counseling in order to reduce body weight (BW) and body mass index (BMI) as well as blood pressure (BP).MethodsA randomized controlled trial was carried out in a rural community in central Thailand.One-hundred and seven adults were randomly allocated (1:2) to intervention and control groups. For 20 weeks, participants in the weight-loss program performed self-weighing twice daily and recorded their weight on the calendar. The program also offers weekly counseling visits by village health volunteers (VHV) who make home visits to participants. The primary outcomes were differences in mean change in BW at 20 weeks from baseline between the intervention and control groups.ResultsA total of 107 participants were initially recruited. Of these, 36 participants were allocated to the intervention group and 57 participants to the control group. Significant differences in mean change in BW and BMI at the twelve-, sixteen-, and twenty-week follow-up from baseline between the two groups were observed. At twenty weeks, the mean change in BW was -1.2 kg (95% CI: -2.2, -0.3) and 0.3 kg (95% CI: -0.3, 0.8) in the intervention and control groups, respectively, with p-value = 0.007. Over 20 weeks of the study period, the estimated mean change in BW among the intervention group was 1.0 kg (95% CI -1.7, -0.2) lower than in the control group, with p-value = 0.015. Furthermore, changes in mean BMI and BP over the 20-week follow-up period in intervention participants were recognized.ConclusionsOur study demonstrates that daily self-weighing combined with personalized counseling led by VHV is feasible and can induce weight loss among adults with obesity in a rural community. In addition, the weight-loss program may be a promising additional tool for reducing BP.Trial registrationTrial identification number was TCTR20201020004; first submitted date: 20/10/2020.

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab

Objective Zanubrutinib is a highly selective, next-generation Bruton’s tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients’ health-related quality-of-life (HRQoL). Methods In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires’ scales and a mixed model for repeated measures was performed using the key QLQ-C30 endpoints of global health status/QoL (GHS/QoL), physical and role functioning, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting at weeks 12 and 24. Results Compared with BR-treated patients, those in the zanubrutinib arm experienced greater improvements in HRQoL outcomes at both weeks 12 and 24. By week 24, mean change differences (95% confidence interval) between the arms were significant for GHS/QoL (4.9 [0.9, 9.0]), physical functioning (3.8 [0.8, 6.7]), diarrhea (−6.2 [−10.0, −2.5]), fatigue (−4.5 [−8.9, −0.1]), and nausea/vomiting (−4.5 [−8.9, −0.1]); role functioning (4.8 [−0.2, 9.7]) was marginally better in the zanubrutinib arm and there were no differences in pain symptoms (−0.4 [−4.3, 5.1]) between the arms. Conclusions During the first 24 weeks of treatment, zanubrutinib was associated with better HRQoL outcomes in patients with treatment-naive CLL/SLL without del(17p) compared to BR. Trial registration The SEQUOIA trial is registered on clinicaltrials.gov as SEQUOIA trial (NCT03336333).

The potential of a multimodal digital care program in addressing healthcare inequities in musculoskeletal pain management

Digital interventions have emerged as a solution for time and geographical barriers, however, their potential to target other social determinants of health is largely unexplored. In this post-hoc analysis, we report the impact of social deprivation on engagement and clinical outcomes after a completely remote multimodal musculoskeletal (MSK) digital care program managed by a culturally-sensitive clinical team. Patients were stratified in five categories according to their social deprivation index, and cross-referenced with their race/ethnicity, rurality and distance to healthcare facilities. From a total of 12,062 patients from all U.S. states, 8569 completed the program. Higher social deprivation was associated with greater baseline disease burden. We observed that all categories reported pain improvements (ranging from −2.0 95%CI −2.1, −1.9 to −2.1 95%CI −2.3, −1.9, p < 0.001) without intergroup differences in mean changes or responder rates (from 59.9% (420/701) to 66.6% (780/1172), p = 0.067), alongside reduction in analgesic consumption. We observed significant improvements in mental health and productivity across all categories, with productivity and non-work-related functional recovery being greater within the most deprived group. Engagement was high but varied slightly across categories. Together these findings highlight the importance of a patient-centered digital care program as a tool to address health inequities in musculoskeletal pain management. The idea of investigating social deprivation within a digital program provides a foundation for future work in this field to identify areas of improvement.

Effectiveness of an individually tailored complex intervention to improve activities and participation in nursing home residents with joint contractures (JointConEval): a multicentre pragmatic cluster-randomised controlled trial

ObjectiveThis study aims to examine the effects of the individually tailored complex intervention Participation Enabling Care in Nursing (PECAN) on activities and participation of residents with joint contractures.DesignMulticentre pragmatic cluster-randomised...

Evaluation of the Early Adolescent Skills for Emotions (EASE) intervention in Lebanon: A randomized controlled trial

BackgroundThere is a need for scalable evidence-based psychological interventions for young adolescents experiencing high levels of psychological distress in humanitarian settings and low- and middle-income countries. Poor mental health during adolescence presents a serious public health concern as it is a known predictor of persistent mental disorders in adulthood. This study evaluates the effectiveness of a new group-based intervention developed by the World Health Organization (Early Adolescent Skills for Emotions; EASE), implemented by non-specialists, to reduce young adolescents' psychological distress among mostly Syrian refugees in Lebanon. MethodsWe conducted a two-arm, single-blind, individually randomized group treatment trial. Adolescents aged 10 to 14 years who screened positive for psychological distress using the Pediatric Symptom Checklist (PSC) were randomly allocated to EASE or enhanced treatment as usual (ETAU) (1:1.6). ETAU consisted of a single scripted psycho-education home-visit session with the adolescent and their caregivers. EASE consists of seven group sessions with adolescents and three sessions with caregivers. The primary outcome was adolescent-reported psychological distress as measured with the PSC (internalizing, externalizing, and attentional symptoms). Secondary outcomes included depression, posttraumatic stress, well-being, functioning, and caregivers' parenting and distress. All outcomes were assessed at baseline, endline, and 3 months (primary time point) and 12 months follow-up. ResultsDue to the COVID-19 pandemic and other adversities in Lebanon at the time of this research, the study was prematurely terminated, resulting in an under-powered trial sample (n = 198 enrolled compared to n = 445 targeted). We screened 604 children for eligibility. The 198 enrolled adolescents were assigned to EASE (n = 80) and ETAU (n = 118), with retention rates between 76.1 and 88.4% across all timepoints. Intent-to-treat analyses demonstrated no between-group differences on any of the outcome measures between the EASE and ETAU. We did observe a significant improvement on the primary outcome equally in the EASE and ETAU groups (−0.90, 95% CI: −3.6, 1.8; p = .52), − a trend that was sustained at three months follow-up. Sub-group analyses, for those with higher depression symptoms at baseline, showed ETAU outperformed EASE on reducing depression symptoms (difference in mean change = 2.7, 95% CI: 0.1, 5.3; p = .04; d = 0.59) and internalizing problems (difference in mean change 1.0, 95% CI: 0.08, 1.9; p = .03; d = 0.56) . ConclusionNo conclusions can be drawn about the comparative effectiveness of the intervention given that the sample was underpowered as a result of early termination. Both EASE and single session psycho-education home visits resulted in meaningful improvements in reducing psychological distress. We did not identify any indications in the data suggesting that EASE was more effective than a single session family intervention in the context of the COVID-19 pandemic and other crises in Lebanon. Fully powered research is needed to evaluate the effectiveness of EASE.

Patients’ experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results

PurposeTo describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway.MethodsParticipants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary).Results99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician.ConclusionThe data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

Biomechanical effect of neurologic dance training (NDT) for breast cancer survivors with chemotherapy-induced neuropathy: study protocol for a randomized controlled trial and preliminary baseline data

BackgroundBreast cancer (BC) is among the most common forms of cancer experienced by women. Up to 80% of BC survivors treated with chemotherapy experience chemotherapy-induced neuropathy (CIN), which degrades motor control, sensory function, and quality of life. CIN symptoms include numbness, tingling, and/or burning sensations in the extremities; deficits in neuromotor control; and increased fall risk. Physical activity (PA) and music-based medicine (MBM) are promising avenues to address sensorimotor symptoms. Therefore, we propose that we can combine the effects of music- and PA-based medicine through neurologic dance training (NDT) through partnered Adapted Tango (NDT-Tango). We will assess the intervention effect of NDT-Tango v. home exercise (HEX) intervention on biomechanically-measured variables. We hypothesize that 8 weeks of NDT-Tango practice will improve the dynamics of posture and gait more than 8 weeks of HEX.MethodsIn a single-center, prospective, two-arm randomized controlled clinical trial, participants are randomly assigned (1:1 ratio) to the NDT-Tango experimental or the HEX active control intervention group. Primary endpoints are change from baseline to after intervention in posture and gait. Outcomes are collected at baseline, midpoint, post, 1-month follow-up, and 6-month follow-up. Secondary and tertiary outcomes include clinical and biomechanical tests of function and questionnaires used to compliment primary outcome measures. Linear mixed models will be used to model changes in postural, biomechanical, and PROs. The primary estimand will be the contrast representing the difference in mean change in outcome measure from baseline to week 8 between treatment groups.DiscussionThe scientific premise of this study is that NDT-Tango stands to achieve more gains than PA practice alone through combining PA with MBM and social engagement. Our findings may lead to a safe non-pharmacologic intervention that improves CIN-related deficits.Trial registrationThis trial was first posted on 11/09/21 at ClinicalTrials.gov under the identifier NCT05114005.

Revisiting efavirenz in the era of dolutegravir: Low-dose efavirenz, a viable alternative capable of holding its own against dolutegravir-based regimens

ABSTRACT Background: First-line dual NRTI + NNRTI-based ART has shown good virological effectiveness; however, toxicity is common and is often the most common reason for modification of first-line ART. Aims: The purpose of this study is to revisit low-dose efavirenz (EFV) in the era of dolutegravir (DTG) by investigating anti-retroviral therapy (ART) switch strategies for outcomes of virological effectiveness and safety in virologically suppressed Indian persons living with HIV (PLH) on first-line dual nucleoside reverse transcriptase inhibitors (NRTI) + non-NRTI (NNRTI)-based ART. Methods: A phase-IV comparative study of consecutive cases who switched their first-line NNRTI-based ART to either EFV-400 or DTG with a dual NRTI backbone between October 2020 to December 2021 and underwent at least 48 weeks of follow-up. The study is a non-randomised trial, wherein ART regimens were based on physician choice, patient preference and drug availability. Results: A total of 102 [DTG arm: 52; EFV-400 arm: 50; intention-to-treat (ITT) population] participants met the inclusion criteria. At 48-week follow-up, virological failure was not observed in either arm. Virological suppression to &lt; 200 cp/mL was attained in 97.9% (n = 48/49; 95% confidence interval [CI]: 89.1–99.9) and 95.9% (n = 47/49; 95% CI: 86.02–99.5) of patients, respectively, in the DTG and-EFV-400 arm (ITT-populations). There was no significant difference in mean change from baseline in body weight and body mass index between DTG and-EFV-400 arms. The proportion of patients who gained ≥ 10% of their baseline body weight at 24 weeks of exposure to DTG was 16% (n = 8, 95% CI: 5.8 to 26.2) and that to EFV-400 was 10% (n = 5, 95% CI: 1.7 to 18.3) with a difference in proportions: 6.0% (95% CI: −7.1–19.1)]. There was a significant decrease at 24 weeks in mean fasting levels of lipid fractions in the DTG arm as compared to EFV-400 [total cholesterol: − 24.3 mg/dL, 95% CI: −35.2 to − 13.3 vs. −6.9 mg/dL, 95% CI: −17.9–4.1 (P = 0.029) and triglycerides:−35.9 mg/dL, 95% CI: −60.9 to − 10.9 vs. 8.6 mg/dL, 95% CI: −16.6 to 33.8 (P = 0.014)]. Adverse events (AEs) of any grade including laboratory derangements to DTG were experienced by 6% (n = 3, 95% CI: −0.6 to 12.6) and that to EFV-400 by 8% (n = 4, 95% CI: 0.5 to 15.5) with a difference in proportions: 2.0% (95% CI: −7.9 to 11.9). Grades 3–4-AE occurred in two patients, both in the EFV-400 arm. Central nervous system AEs were not observed in the DTG arm and occurred in two patients in the EFV-400 arm. Two patients in the EFV-400 arm discontinued the regimen due to AEs. Conclusion: Both DTG and EFV-400-based first-line ART show good virological effectiveness and safety profiles in patients who are virologically suppressed on dual NRTI + NNRTI-based first-line ART.

Effects of Synbiotic-Containing Bacillus coagulans (GBI-30) on the Cardiovascular Status of Patients With Polycystic Ovary Syndrome: A Triple-blinded, Randomized, Placebo-controlled Study

PurposeDespite the high risk of cardiovascular diseases in women with polycystic ovary syndrome, fewer studies have addressed the improvement of cardiometabolic status of these patients. This study was conducted with the aim of investigating the effects of synbiotic-containing, spore-forming Bacillus coagulans on cardiometabolic indicators, including lipid profile, C-reactive protein, and atherogenic indexes in patients with polycystic ovary syndrome. MethodsIn the present 12-week, triple-blinded, randomized, placebo-controlled clinical trial, 72 women with polycystic ovaries were randomized to receive either 2 g of synbiotic sachet (n = 36) or placebo (n = 36) plus lifestyle modification. Fasting blood samples were taken before and after the intervention. FindingsStatistical analysis was performed in 60 participants with a mean (SD) age of 28.25 (5.98) years who completed the intervention (synbiotic group [n = 34] and placebo group [n = 26]). A significant mean (SD) decrease in C-reactive protein level was observed in the synbiotic group compared with the placebo group (−0.12 [9.57] v. −0.008 [4.69], P = 0.03). No significant differences in mean changes of lipid profile and atherogenic indexes were seen between the 2 groups. Although the estimated mean changes in atherogenic indexes in the synbiotic group indicates a greater reduction than the placebo group, no significant difference was detected. ImplicationsOur 12-week synbiotic intervention improved the inflammatory status in women with polycystic ovaries without affecting lipid profile or atherogenic indexes.

Multicomponent Home-based Physical Therapy Versus Usual Care for Recovery After Hip Fracture

ObjectiveTo quantify the effect of 2 home-based 16-week multi-component physical therapy interventions on functional recovery compared to usual care after hip fracture. DesignCross-study comparison using participants from the Community Ambulation Project (CAP; a randomized controlled trial) were compared to the Baltimore Hip Studies-seventh cohort (BHS-7; an observational cohort study) at 3 different time points (CAP: 15, 31, 55 weeks; BHS-7: 8, 26, and 52 weeks). SettingGeneral community ParticipantsCombined convenience sample of hip-fracture patients 8-26 weeks post admission from a prospective cohort study and randomized controlled trial. (N=549) InterventionsCAP participants were randomized to one of 2 interventions (PUSH: specific multi-component intervention; PULSE: non-specific multi-component intervention) after standard rehabilitation; BHS-7 participants received usual care. Main Outcome MeasuresMean function (as measured by Short Physical Performance Battery (SPPB) and gait speed) was estimated in each cohort as quadratic functions of time using data from 3 post-fracture assessments in both studies (CAP: 15, 31, 55 weeks; BHS-7: 8, 26, and 52 weeks). ResultsThe harmonized samples included 101 PUSH, 100 PULSE, and 128 BHS-7 participants that had different demographic and clinical characteristics. Mean baseline SPPB scores (meters per second) were PUSH: 5.5 (SD=2.2), PULSE: 5.5 (SD=2.4), and BHS-7: 4.6 (SD=2.5); and mean gait speeds were 0.60 m/s (SD=0.20) for PUSH, 0.59 m/s (SD=0.17) for PULSE, and 0.46 m/s SD=(0.21) for BHS-7, respectively. Estimated between-group differences for SPPB improvement from 75 days to 1-year post admission were 0.7 (P=.04) in PUSH vs BHS-7; and 0.9 (P=.01) in PULSE vs BHS-7. Mean differences in change in gait speed were 0.08 (P=.002) for PUSH vs BHS-7; and 0.06 (P=.02) PULSE vs BHS-7 (P=.02). ConclusionsFindings from this cross-study comparison that combined participants from 2 separate studies, with different designs and samples, suggest that home-based multi-component physical therapy programs were associated with greater functional improvement after hip fracture compared to usual care.