Baseline Week Research Articles

Evaluation of liver function tests to identify hepatotoxicity among acute lymphoblastic leukemia patients who are receiving chemotherapy induction

The effect of induction chemotherapy on liver function in patients with acute lymphoblastic leukemia is not well documented in Ethiopia. This study assessed hepatotoxicity in patients with acute lymphoblastic leukemia who were undergoing induction chemotherapy in Ethiopia. A 1-month cohort study was undertaken in forty patients with acute lymphoblastic leukemia, with measurements taken at the baseline, second, and fourth weeks. A Log 10 transformation was done because of the skewed distribution of liver function tests. Descriptive statistics such as mean and proportion were calculated. A mixed model ANOVA and Bonferroni post hoc test were computed. A p value < 0.05 was declared to determine statistical significance. Clinically significant hepatotoxicity was observed in 15% of patients. Mild liver injury occurred in 5% of patients. The mean of all liver function tests increased significantly from pre-induction to post-induction. ALT levels were significantly higher in patients who received blood transfusions, but not in those who did not. Regardless of other factors, ALP level in children is significantly higher than in adults, although total bilirubin in adults is higher than in children. A significant proportion of patients had hepatotoxicity. During chemotherapy induction, the mean of all liver function tests rose significantly, but this elevation of serum liver function tests may be transient. Chemotherapy drugs should be given without causing a significant alteration in serum liver function tests. Continuous monitoring of patients should be required.

Effect of fixed 7.5 minutes' moderate intensity exercise bouts on body composition and blood pressure among sedentary adults with prehypertension in Western-Kenya.

Prehypertension is a modifiable risk factor for cardiovascular disease observed to affect an estimated 25-59% of global population and closely associated with body composition. Without appropriate interventions, one-third of individuals with prehypertension would develop full-blown hypertension within 4 years. The existing exercise recommendations need substitutes that appeal more yet accord similar or better outcomes in desire to halt this progression. This study evaluated the effect of Fixed 7.5-minute Moderate Intensity Exercise (F-7.5m-MIE) bouts on Body Composition and Blood Pressure (BP) among sedentary adults with prehypertension in Western-Kenya in a Randomized Control Trial (RCT) performed throughout the day compared to the single-continuous 30-60-minute bouts performed 3 to 5 times weekly. This RCT, with three arms of Experimental Group1 (EG1) performing the F-7.5m-MIE bouts, Experimental Group 2 (EG2) performing current World Health Organization (WHO) recommendation of ≥30-min bouts, and, control group (CG), was conducted among 665 consenting pre-hypertensive sedentary adults enrolled from western Kenya. EG1 and EG2 performed similar weekly cumulative minutes of moderate intensity exercises. Adherence was determined using activity monitors and exercise logs. Data regarding demographic characteristics, heart rate, BP, and anthropometric measures were collected at baseline and 12th week follow-up. Data regarding univariate, bivariate and multivariate (repeated measurements between and within groups) analysis were conducted using STATA version 13 at 5% level of significance. The study revealed that males (92.1% in EG1, 92% in EG2 and 96.3% in CG) and females (94.6% in EG1, 89.3% in EG2 and 95% in CG) in the three arms completed the exercise at follow-up respectively. At 12th week follow-up from all exercise groups, males' and females' measurements for waist-hip-ratio, waist-height-ratio, systolic BP (SBP), heart rate and pulse pressure showed significant drops from baseline, while diastolic BP (DBP) and body mass index (BMI) reported mixed results for males and females from the various treatments. Both treatments demonstrated favourable outcomes. However, differences in the change between baseline and endpoint yielded mixed outcomes (SBP; p<0.05 for both males and females, DBP; p<0.05 for males and females, waist-height-ratio; p = 0.01 and <0.05 for males and females respectively, waist-hip-ratio; P = 0.01 and >0.05 for males and females respectively, BMI; p>0.05 for both males and females, heart rate; p<0.05 for males and females and pulse pressure; p = 0.01 and >0.05 for males and females respectively). The study design however could not test for superiority. The study demonstrated that the F-7.5m- MIE treatment programme and the WHO recommended 3-5 times weekly bouts of 30-60 minutes regime produced comparably similar favourable outcomes in adherence and BP reductions with improved body composition. Trial registration: Trial registered with Pan African Clinical Trial Registry (www.pactr.org): no. PACTR202107584701552. (S3 Text).

Multiple positive outcomes of a later school starting time for adolescents

ObjectiveWe tested the effect of later school start time (LSST) by 1 hour during 1 week on sleep, sleepiness, and mood profile using within-subject design. DesignA within-subject 3-weeks-long interventional study. A baseline week with school starting at 7:30 AM (week A), followed by an intervention week with school starting at 8:30 AM (week B), and a recovery week with school start time back to 7:30 AM (week C). Mixed model for repeated measures analysis was applied to test for the LSST effect between weeks. SettingA private high school with high level of socioeconomic status. ParticipantsForty-eight adolescents from 3 different high school years. MeasurementsParticipants were invited to wear actigraphs continuously during the 3 experimental weeks. Somnolence was obtained every school day twice, at arrival and before departure of school. Sleep quality and mood profile were evaluated by standard measures by the end of each school week, resulting in 3 repeated measures for each variable. ResultsThirty-eight adolescents completed the study. Adolescents woke up later during week B (7:42 ± 00:30) in comparison to weeks A (6:54 ± 00:12) and C (6:46 ± 00:15) (p < .001), with no significant change on sleep onset between weeks (p = .657), resulting in a longer sleep duration in week B (p < .001). Significant improvements on sleepiness and mood profile were also reported during week B. ConclusionsStarting school later was effective in improving multiple aspects from sleep patterns, subjective sleepiness, and mood profile.

Effect of Exercise Instructions With Ambulatory Accelerometer in Japanese Patients With Type 2 Diabetes: a Randomized Control Trial.

This study aimed to investigate the effects of physical therapists’ exercise instructions in Japanese patients with type 2 diabetes. Thirty-six participants were recruited from the outpatient clinic at Matsushita Memorial Hospital, Osaka, Japan from June 2020 to September 2020 and were randomly assigned to either the non-intervention or intervention group. The intervention group received exercise instructions from physical therapists for 30 min at baseline (week 0) and at week 4 by referring to ambulatory accelerometer records. Laboratory parameters, physical activity, body composition, motor skill, and transtheoretical model were assessed in both the groups at baseline (week 0) and week 8. In week 8, patients in the intervention group had a statistically significant reduction in HbA1c levels compared with those in the non-intervention group (7.3% [6.8-%–7.9%] vs. 7.4% [7.3%–7.7%], P = 0.04). The number of steps per day (P = 0.001), energy expenditure (P = 0.01), lower extremity muscle strength (P = 0.002), and 6-min walk test results (P = 0.04) were significantly increased in the intervention group compared with those in the non-intervention group in week 8. The transtheoretical model varied between baseline (week 0) and week 8 only in the intervention group (P < 0.001). Thus, outpatient exercise instructions from physical therapists could improve glycemic control owing to physical activity by improving motor skills and changing the transtheoretical model in Japanese patients with type 2 diabetes.

Efficacy of acceptance and commitment therapy focused on repetitive negative thinking in fibromyalgia: A randomized multiple-baseline design

Repetitive negative thinking (RNT), in the form of worry and rumination, is a factor that can have a negative impact on the quality of life and symptomatology of patients with fibromyalgia (FM). The present study analyzes the efficacy of a brief Acceptance and Commitment Therapy (ACT) protocol focused on reducing RNT in four women diagnosed with FM. A randomized, multiple-baseline design across participants was conducted. Participants completed 4-6 weeks of baseline and subsequently received a 4-session individual intervention. The effect of the intervention was assessed by conducting follow-ups for up to 3 months. All four participants showed clinically significant changes in emotional symptoms as measured by the Depression Anxiety and Stress Scale – 21 (DASS-21¸ S. H. Lovibond y P. F. Lovibond, 1995) and the General Health Questionnaire – 12 (Ruiz et al., 2017a). Likewise, participants showed significant improvements in parameters related to sleep quality and improvements in health-related quality of life. As for process measures, all participants showed clinically significant changes in pathological worry, and three of them also in cognitive fusion. Changes in valued actions were more modest. Effect sizes comparable across designs were very large and statistically significant for DASS-Total (d = 1.51), DASS-Depression (d = 1.83), pathological worry (d = 1.79), and cognitive fusion (d = 1.99). These results suggest that brief RNT-focused ACT interventions hold promise for intervention in patients with FM.

Effects of Scapular Proprioceptive Neuromuscular Facilitation Techniques in Addition to Routine Physical Therapy on Clinical Outcomes in Patients with Adhesive Capsulitis: A Randomized Controlled Trial

Background: Adhesive capsulitis is a painful condition comprises of reduced glenohumeral joint movement and the scapular neuromuscular facilitation techniques is considered effective, non-invasive approach for treating this condition. Objective: To compare the effects of neuromuscular facilitation techniques on clinical outcomes in patients with adhesive capsulitis. Methods: This trial was registered in ClinicaTrials.gov (ref: NCT05151783) and approval was taken (IRB No. 818-II). This single-blinded randomized controlled trial was conducted on patients (n=96) having adhesive capsulitis in six months. Non-probability purposive sampling technique was used for randomization via sealed envelope method. Conventional group received routine physiotherapy including ultrasound, hot packs, shoulder range of motion, stretching exercises, and joint mobilization five times per week for four weeks with 40 minutes’ duration of each session. Glenohumeral joint distraction, caudal, dorsal, and ventral glides were given at a rate of 2-3/second oscillations for 1-2 minutes to patients. Visual analogue scale, functional activity was calculated at baseline, 2nd and 4th week. The descriptive statistics (continuous variables) values for each variable in form of means and standard deviations were calculated and their p-values were also calculated using an independent sample t-test. For the qualitative data (categorical variables), frequency and percentage were estimated. Frequencies and percentages of different variables like gender had also been calculated. Repeated measure analysis of variance (ANOVA) was calculated to calculate within-group differences in the mean of each variable between the assessment points. Results: Test of within subject effects showed significant difference for all variables at follow-up and difference between groups also showed significant difference at different follow-ups (p-value≤0.001). Both groups showed statistically significant results (p≤0.001), but scores were higher in experimental group. Conclusion: Scapular proprioceptive neuromuscular facilitation technique along with routine physical therapy are more effective as compared to routine physical therapy alone in patients with adhesive capsulitis.

A Progressive Loading Supervised Exercise Program and Manual Therapy for The Management of Lateral Elbow Tendinopathy: A Case Report

The purpose of the case study was to find out the effect of a supervised exercise program combined with Transverse Friction (TF) and Mulligan Mobilization With Movement (MMWM) on disability and pain in a patient experiencing chronic Lateral Elbow tendinopathy (LET). A patient with unilateral LET for 6 months was included in the present study. The patient followed the exercise program five times per week for 4 weeks. The programme was individualized on the basis of the patient’s description of pain experienced during the procedure. TF and MMWM were applied 3 times per weeks for 4 weeks, 12 sessions totally. Outcome measures were function using the Patient-Rated Tennis Elbow Evaluation, a visual analogue scale and the pain-free grip strength and pain using a visual analogue scale. The patient was evaluated at baseline (week 0), at week 4 (end of treatment), at week 8 (1 month after the end of the treatment) and at week 32 (six months after the end of treatment). At the end of the treatment and at the follow – up there was a rise in function and a decline in pain. The findings of the case report suggest that a physiotherapy approach as described in the present case report can produce significant improvements in terms of disability and pain in a patient with chronic LET

VITAMIN E AND ITS EFFECTIVENESS IN MANAGEMENT OF GRADE II &amp; III HAEMORRHOIDS

Objective: The aim of the study is to evaluate the effectiveness of vitamin E due to its potent antioxidant with anti-inflammatory properties by assessing Vitamin E levels and Visual analogue scale. Methods: This prospective randomized study was carried out for a period of 4 months in private hospital, Chennai. A total of 30 patients were enrolled based on the inclusion and exclusion criteria and were randomized into 2 groups Group A (standard treatment) and Group B (standard treatment plus vitamin E oral supplement).The effectiveness was observed by assessing vitamin E levels and VAS score at baseline, 1st, 3rd and 5th week after the start of oral vitamin E supplementation. Results: In total, 30 patients were randomized into Group A and Group B with 15 patients each. Among 30 patients 18 patients were males and 12 patients were females. In that 7 patients in age group 18-25 years, 13 patients in age group 26-35 years, 8 patients in age group 36-45 years and 2 patients were above 45 years of age At baseline, the average range of intensity of pain was 6, at 1st week the VAS score was 6 in Group A and 4 in Group B, at 3rd week 5 in Group A and 3 in Group B and at 5th week 4 in Group A and 1 in Group B. Based on Vitamin E levels, the average level at base line was 5 in Group A and 4.1 in Group B, followed by 5 in Group A and 4.5 in Group B at 1st week, 4.8 in Group A and 5.6 in Group B at 3rd week, and 4.7 in Group A and 7 in Group B at 5th week. Conclusion: Our study concluded that the vitamin E levels increased and the intensity of pain has reduced after receiving vitamin E oral supplementation along with standard treatment which was a good sign for its effectiveness in haemorrhoids Keywords: Haemorrhoids, Vitamin E, alpha-tocopherol, oxidative stress, antioxidant

Comparison between radial and focused types of extracorporeal shock-wave therapy in plantar calcaneal spur: A randomized sham-controlled trial

ABSTRACT Objectives Both radial and focused types of extracorporeal shock wave therapy (ESWT) have been used in patients with plantar calcaneal spur (PCS). However, no study has yet addressed the comparative effects of these treatments on the condition. Considering radial and focused waves are different from each other, their effectiveness may also be different in clinical practice. The aim of this study was to compare the effects of radial and focused types of ESWT on PCS. Methods Ninety-nine patients with plantar calcaneal spur were randomised into three groups according to ESWT types: focused, radial, and sham. ESWT was applied as three sessions, with 2–4 days intervals (excluding weekends). All patients were evaluated at baseline (week 0) and weeks 1, 5, and 13. The Foot Function Index (FFI) scores were used as outcome measures. Results Compared with baseline (week 0), at the end of treatment (week 1) and at the follow-up periods (weeks 5, and 13) the FFI scores were significantly reduced in both focused and radial ESWT groups (for all, p < 0.001). When considering the change in data from baseline to follow-up periods (weeks 5, and 13), both focused and radial ESWT groups were significantly superior to the sham group in the all outcome measures (for all, p < 0.05). Importantly, the radial group was significantly superior to focused group based on the changes in the FFI scores (for all, p < 0.05). Conclusion Both focused ESWT and radial ESWT are effective in plantar calcaneal spur. When considering the degree and continuity of the positive effects, radial ESWT is superior to focused ESWT in plantar calcaneal spur.

Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program.

This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks' treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes. STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0-68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR) among participants with prediabetes (post hoc). Significantly more participants with baseline (week 0) prediabetes (n = 1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01). STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks' treatment with semaglutide versus placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia.

Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment.

IntroductionSince the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines.Materials and methodsTo longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses.ResultsA total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate.ConclusionWhile the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

A Theory-Informed, Personalized mHealth Intervention for Adolescents (Mobile App for Physical Activity): Development and Pilot Study.

BackgroundEvidence suggests that physical activity (PA) during childhood and adolescence is crucial as it usually results in adequate PA levels in adulthood. Given the ubiquitous use of smartphones by adolescents, these devices may offer feasible means to reach young populations and deliver interventions aiming to increase PA participation and decrease sedentary time. To date, very few studies have reported smartphone-based interventions promoting PA for adolescents. In addition, most available fitness apps do not include the latest evidence-based content.ObjectiveThis paper described the systematic development of a behavior change, theory-informed Mobile App for Physical Activity intervention with personalized prompts for adolescents aged 16 to 18 years. The within-subject trial results provided the first evidence of the general effectiveness of the intervention based on the outcomes step count, sedentary time, and moderate to vigorous PA (MVPA) minutes. The effectiveness of the intervention component personalized PA prompt was also assessed.MethodsA 4-week within-subject trial with 18 healthy adolescents aged 16 to 18 years was conducted (mean age 16.33, SD 0.57 years). After the baseline week, the participants used the Mobile App for Physical Activity intervention (Fitbit fitness tracker+app), which included a daily personalized PA prompt delivered via a pop-up notification. A paired 1-tailed t test was performed to assess the effectiveness of the intervention. Change-point analysis was performed to assess the effectiveness of a personalized PA prompt 30 and 60 minutes after prompt delivery.ResultsThe results showed that the intervention significantly reduced sedentary time in adolescents during the first week of the trial (t17=−1.79; P=.04; bootstrapped P=.02). This trend, although remaining positive, diminished over time. Our findings indicate that the intervention had no effect on metabolic equivalent of task–based MVPA minutes, although the descriptive increase may give reason for further investigation. Although the results suggested no overall change in heart rate–based MVPA minutes, the results from the change-point analyses suggest that the personalized PA prompts significantly increased heart rate per minute during the second week of the study (t16=1.84; P=.04; bootstrapped P=.04). There were no significant increases in participants’ overall step count; however, the personalized PA prompts resulted in a marginally significant increase in step counts per minute in the second week of the study (t17=1.35; P=.09; bootstrapped P=.05).ConclusionsThe results of the trial provide preliminary evidence of the benefit of the Mobile App for Physical Activity intervention for modest yet significant reductions in participants’ sedentary time and the beneficial role of personalized PA prompts. These results also provide further evidence of the benefits and relative efficacy of personalized activity suggestions for inclusion in smartphone-based PA interventions. This study provides an example of how to guide the development of smartphone-based mobile health PA interventions for adolescents.

Initial eGFR Changes with Ertugliflozin and Associations with Clinical Parameters: Analyses from the VERTIS CV Trial

Introduction: Using data from the ertugliflozin cardiovascular outcomes trial in patients with type 2 diabetes mellitus (VERTIS CV; NCT01986881), associations between the initial estimated glomerular filtration rate (eGFR) “dip” with eGFR slope, glucosuria/natriuresis-related measures, and safety were investigated. Methods: Patients were categorized into tertiles based on change in eGFR at week 6: >+1.00 mL/min/1.73 m² (tertile 1), >−5.99 and ≤+1.00 (tertile 2), and ≤−6.00 (tertile 3). eGFR slope after week 6 and week 18 was assessed by tertile. Glucosuria/natriuresis-related measures were also determined. Adverse events (AEs) were analyzed in the acute (baseline–week 6) and chronic periods (week 6–30 days after last dose of trial medication). Results: In the ertugliflozin group, chronic eGFR slopes (95% CI, mL/min/1.73 m²/year; weeks 6–156) were −0.76 (−1.03, −0.50), −0.29 (−0.51, −0.07), and −0.05 (−0.26, 0.17) in tertiles 1, 2, and 3, respectively (p value <0.001), and approximately −1.5 mL/min/1.73 m²/year across tertiles in the placebo group (p value = 0.79). At week 18, least squares mean (LSM) changes from baseline in glycated hemoglobin (%) were −0.77, −0.71, and −0.67 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; a similar tertile-associated trend was observed for uric acid. At week 18, LSM changes from baseline in hematocrit (%) were 2.07, 2.33, and 2.55 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; similar tertile-associated trends were observed for blood pressure. All p_interaction values were <0.0001 for glucosuria- and natriuresis-related measures. Kidney-related AEs were reported more frequently in tertiles 3 and 2 in the chronic period for both placebo- and ertugliflozin-treated groups. In both periods and in all tertiles, incidences of AEs did not differ between placebo- and ertugliflozin-treated groups. Conclusion: With ertugliflozin, the tertile with the largest initial dip in eGFR had a slower rate of chronic eGFR decline. Initial eGFR changes were associated with changes in both glucosuria- and natriuresis-related measures.

Intramuscular administration of autologous total immunoglobulin G induces immunomodulatory effects on T cells in healthy human subjects: An open-labeled prospective single-arm trial.

Background:We hypothesized that intramuscular administration of autologous total immunoglobulin G (IgG) could induce an immunomodulatory effect in human subjects. In our previous studies, we showed that intramuscular administration of autologous total IgG could induce significant clinical improvements and increases of the serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-γ) in patients with atopic dermatitis.Objective:To investigate the mechanism of immunomodulation induced by intramuscular administration of autologous total IgG, we evaluated changes in T cells before and after intramuscular administrations of autologous total IgG in this study.Methods:Thirteen healthy adults received 8 intramuscular injections of 50 mg autologous total IgG for 4 weeks (from week 0 to week 4). The percentages of IL-10- or IFN-γ-producing peripheral blood T cells, as well as serum levels of IL-10, IFN-γ, and immunoglobulins, were measured at baseline (week 0) and at weeks 4, 8, and 12.Results:The percentage of IL-10-producing CD4+ T cells was significantly increased at weeks 8 and 12 compared to baseline (P < .05), while the percentage of IFN-γ-producing CD3+ T cells was significantly increased at week 12 compared to baseline (P < .05). There were no significant differences in the serum levels of IL-10, IFN-γ, and immunoglobulins before and after intramuscular administration of autologous total IgG (P > .05). No serious adverse events were observed.Conclusion:Intramuscular administration of autologous total IgG induced immunomodulatory effects on T cells in healthy human subjects. This simple intervention could be a safe, effective, and economical T cell immunomodulation method for human subjects (NCT03695757).

Open-label, phase 2 study of roxadustat for treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies.

12085 Background: Anemia is prevalent in patients (pts) receiving myelosuppressive chemotherapy (&gt; 60%) and exacerbated by repeated treatment cycles due to cytotoxic agent accumulation. Chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in pts with anemia receiving myelosuppressive chemotherapy. Methods: This open-label, single-arm, proof-of-concept Phase 2 study included pts with mostly advanced, non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had not received red blood cell (RBC) transfusion or erythropoietin-stimulating agents within 4 weeks of enrollment. Patients were treated with oral roxadustat for ≤16 weeks. The primary efficacy endpoint was maximum mean change in Hb within 16 weeks of baseline without RBC transfusion in pts who had received ≥1 dose of roxadustat and who had a baseline and ≥1 post-dose Hb assessment. Hb response and safety data were preliminarily assessed in pts receiving a starting dose of 2.0 mg/kg thrice weekly (TIW) for 4 weeks: doses of 100, 150, and 200 mg were given to pts weighing &lt; 70, 70–100, and &gt; 100 kg, respectively. Following a review of data from these pts, dose was increased to 2.5 mg/kg—150, 200, and 250 mg TIW to pts weighing &lt; 70, 70–100, and &gt; 100 kg, respectively—and adjusted every 4 weeks from Week 5 based on Hb response. Results: Patients were assigned to 2.0 mg/kg (n = 31) and 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The maximum mean Hb change from baseline without RBC transfusion was 2.47±1.51 g/dL and 2.52±1.54 g/dL in the 2.0 mg/kg and 2.5 mg/kg cohorts, respectively. Hb increased by ≥1.5 g/dL in 73% of pts and ≥2.0 g/dL in 61% of pts. Median time to ≥2.0 g/dL Hb increase was 71.0 days. Both cohorts had higher proportions of pts with a Hb increase of ≥1, ≥1.5, or ≥2 g/dL at Week 16 compared with baseline. Median time to ≥1 and ≥2 g/dL Hb increase was shorter in pts who started on 2.5 mg/kg compared with 2.0 mg/kg doses (≥1 g/dL: 30 vs 44; ≥2 g/dL 57 vs 105, respectively). Fewer pts required an RBC transfusion (Week 5 to end of treatment) when starting on 2.5 mg/kg compared with 2.0 mg/kg doses (10.2% vs 20.0%). Subgroup analyses based on major tumor and baseline chemotherapy types demonstrated efficacy of roxadustat at both starting doses. The overall safety profile observed was consistent with the patient population under study. Overall, 92% of pts experienced an adverse event (AE). Most AEs were consistent with the underlying malignancies and chemotherapy regimens used. The incidence of deep vein thrombosis was 15.2% (n = 14) and pulmonary embolism was 9.8% (n = 9). There were 17 deaths (18.5%) during the study; none were attributed to roxadustat, and most were associated with disease progression. Conclusions: Roxadustat increased Hb in CIA regardless of tumor type and chemotherapy regimen. These data support additional clinical study. Clinical trial information: NCT04076943.

Shortening the baseline period in hot flash symptom control trials: Comparison of a one-day versus seven-day baseline hot flash diary.

e24094 Background: Hundreds, if not thousands, of participants are enrolled hot flash trials each year given the magnitude of the problem for breast and prostate cancer survivors. Classically, these studies have included a baseline period of 1-week, or longer, to understand the frequency and severity of hot flashes before starting a new treatment. The objective of the current study was to compare the accuracy of a 1-day baseline hot flash diary to a more traditional 1-week dairy. A shorter baseline period would be more convenient for patients and provide a more efficient study design. Methods: Raw data from 5 pilot studies and 15 phase III randomized, controlled trials (RCTs), all of which used a one-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p-values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate. Results: A total of 2,573 participants were included. On average, participants had 8.5 hot flashes per day on Day 1. Mean hot flash frequencies and scores on subsequent days (Days 2-7) were within 6% of Day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Re-analysis for each pilot study revealed that no individual study conclusions would have been meaningfully altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa. Conclusions: A 1-day hot flash diary appears to accurately reflect true frequency and severity of baseline hot flash symptoms in appropriately sized cohorts. Results support a shorter baseline period for pilot studies and RCTs.

710-P: In Patients with Type 2 Diabetes Mellitus (T2DM) , Continuous Glucose Monitoring System (CGMS) Usage Does Not Alter Multiple Measures of Glycemic Variability (GV)

Background: The RCT data on CGMS and GV in patients with T2DM have used limited measure of GV metrics. In patients with T2DM on CGMS, we examined whether the use of blinded or unblinded CGMS will affect their GV across a broad swatch of metrics. Methods: A randomized control study involving 40 subjects with T2DM was done [50% females, mean (SD) age 59 years (12.5) , BMI 34.kg/m2 (8.1) , mean (SD) screening HbA1c 7.59% (1.2) ]. Patients were randomized (1:1) to either 1 unblinded (Freestyle Libre) +1 blinded (Freestyle Libre Pro) CGMs or 2 blinded CGMS (Freestyle Libre Pro) for 16 weeks. Sensors were replaced every 2 weeks with an in-person visit. Multiple GV metrics were calculated from the blinded CGM at baseline (Week 0-Week2) and end-intervention (Week 14-16) . Participants randomized to the Unblinded/Blinded CGM group were instructed to use the CGM as they wished. Participants randomized to the Blinded CGM group were instructed to continue checking their fingerstick glucose as usual. Measured GV metrics included the following: mean glucose, standard deviation (SD) , and coefficient of variation (CV) , continuous overlapping net glycemic action (CONGA) , liability Index, J-index, low and high blood glucose index (LBGI/HBGI) , glycemic risk assessment diabetes equation (GRADE) , mean of daily differences (MODD) , average daily risk range (ADRR) , mean amplitude of glycemic excursions (MAGE) , mean of daily differences (MODD) , Area Under Curve (AUC) , time spent in range (TIR) , Glucose Management Indicator (GMI) , number of episodes below 55 and glycemic variability percentage (GVP) . Results: In this study, we found that was no significant difference in all GV metrics between the blinded/ blinded CGMS group and unblinded/blinded CGMS group at baseline and end intervention. Conclusion: The novelty of this study is the extensive analysis of GV across multiple metrics in patients with T2DM on CGMS and CGMS usage did not significantly alter GV. Disclosure Y.Lee: None. A.Mehfooz: None. Q.Wang: None. L.S.Chow: Other Relationship; Dexcom, Inc.

Microbiome Modulators and Mood Disorders: Using a Multi-Strain Probiotic - Bio-Kult® Advanced - in Patients With Low Mood

AimsThe aim of this proof-of-concept study was to understand the effect of daily intake of a 14-strain probiotic on mood, reward learning and emotional and cognitive processing in adults with low mood in the absence of prescribed medication. Salivary cortisol was measured as a marker for physiological stress.MethodsIn this parallel-group double-blind, placebo-controlled trial, 80 healthy adults with self-identified low mood were randomised to receive either the 14-strain probiotic or placebo for a duration of 4 weeks. Data were collected from participants at baseline (week 0) and post-intervention (week 4).ResultsProbiotic intake significantly reduced depression scores (by 50%) compared to baseline, as measured by the Patient Health Questionnaire-9 (PHQ-9) scale (p &lt; 0.05). Analysis of individual items in the PHQ-9 revealed that participants taking probiotics reported improved concentration relative to baseline (+ 51%, p &lt; 0.05) and felt less tired compared to placebo (−21%, p &lt; 0.01).Regarding emotional processing, the probiotic group was more accurate at recognising facial expressions compared to those receiving placebo (facial emotion recognition test, +12%, p &lt; 0.05). Furthermore, the probiotic group performed less well at the reward learning task relative to the placebo group (probabilistic instrumental learning task, p &lt; 0.05) and was less vigilant to emotional cues compared neutral cues (dot-probe unmasked test, −8%, P &lt; 0.05). The probiotic group also showed increased susceptibility to emotional interference during a cognitive learning task, relative to placebo (auditory visual learning task, −18% p &lt; 0.05).The study also revealed a downward trend in salivary cortisol in the probiotic group over 4 weeks.Together, these results suggest that probiotics may work via a different psychological mechanism to that of conventional antidepressants. In other words, probiotics may work by reducing emotional salience across all emotions whereas conventional antidepressants are thought to work by increasing bias to positive emotional cues and decreasing bias to negative ones.ConclusionThese data suggest that intake of Bio-Kult® Advanced has an effect on mood and that this is achieved in ways distinct from the effects of pharmacological antidepressants. While more research is needed, these results suggest that certain probiotics could form part of an ‘early intervention’ strategy for people experiencing low mood. A second randomised controlled trial (currently recruiting) will provide data on this intervention in patients with a formal diagnosis of depression undergoing concurrent pharmacological treatment.ClinicalTrials.gov Identifier: NCT03801655

Association of Plasma Folate, Vitamin B12, and Betaine With Total Homocysteine in Pregnancy, and Effect Modification Due to Folic Acid Versus Natural Folate Supplementation

ObjectivesElevated circulating total homocysteine (tHcy) is associated with numerous pregnancy complications. Determinants of circulating tHcy include folate, vitamin B12, and betaine status, which catalyze the remethylation of homocysteine to methionine. In countries with folic acid food fortification, vitamin B12 and betaine are reported as stronger predictors of tHcy than folate. We evaluated the association between plasma folate, vitamin B12, and betaine with plasma tHcy in pregnancy, and any effect modification due to supplementation with folic acid versus 5-methyltetrahydrofolate (natural folate; 5-MTHF).MethodsPregnant women (n = 60) in Vancouver, BC, were randomized to 0.6 mg folic acid or 5-MTHF for 16 weeks, starting at 8–21 weeks gestation. Dietary folate intake was recorded at baseline. A 3-hour fasting blood sample was collected at baseline and endline for quantification of plasma folate (LC-MSMS), vitamin B12 (immunoanalyzer), betaine and tHcy (HPLC-MSMS). Linear regression was used to assess the association of endline plasma folate, vitamin B12, and betaine with endline tHcy, with folate group as an interaction term, adjusting for baseline tHcy, weeks gestation, and dietary folate intake. As the trial is not yet unblinded, groups are presented as “A” and “B”.ResultsThe median [IQR] concentrations of plasma analytes at endline in groups “A” and “B” were: folate 58 [54, 65] and 66 [61, 82] nmol/L; vitamin B12 204 [159,239] and 206 [166,300] pmol/L; betaine 15 [13, 16] and 14 [12, 17] µmol/L; tHcy 4.9 [4.5, 5.6] and 5.2 [4.7, 5.8] µmol/L, respectively. Folate group did not significantly modify the association of tHcy with folate (p = 0.39), vitamin B12 (p = 0.42), or betaine (p = 0.56). Overall, there was no association (β, 95% CI) of endline plasma folate, vitamin B12, or betaine with the outcome tHcy (µmol/L): folate −0.002 (−0.01 to 0.009); tB12 −0.0005 (−0.002 to 0.0005); betaine 0.02 (−0.04 to 0.07). Baseline tHcy was the most significant predictor of endline tHcy in each model (β = 0.8, 95% CI 0.6 to 1.0).ConclusionsFolate, vitamin B12, and betaine concentrations were not associated with tHcy, nor was the effect modified by supplementation with folic acid versus 5-MTHF. In this group of n = 60 healthy pregnant women, baseline tHcy was the most important predictor of tHcy in later pregnancy.Funding SourcesHealthy Starts Catalyst Grant (BCCHR).

Morning Exercise Reduces Abdominal Fat and Blood Pressure in Women; Evening Exercise Increases Muscular Performance in Women and Lowers Blood Pressure in Men.

The ideal exercise time of day (ETOD) remains elusive regarding simultaneous effects on health and performance outcomes, especially in women. Purpose: Given known sex differences in response to exercise training, this study quantified health and performance outcomes in separate cohorts of women and men adhering to different ETOD. Methods: Thirty exercise-trained women (BMI = 24 ± 3 kg/m2; 42 ± 8 years) and twenty-six men (BMI = 25.5 ± 3 kg/m2; 45 ± 8 years) were randomized to multimodal ETOD in the morning (0600–0800 h, AM) or evening (1830–2030 h, PM) for 12 weeks and analyzed as separate cohorts. Baseline (week 0) and post (week 12) muscular strength (1-RM bench/leg press), endurance (sit-ups/push-ups) and power (squat jumps, SJ; bench throws, BT), body composition (iDXA; fat mass, FM; abdominal fat, Abfat), systolic/diastolic blood pressure (BP), respiratory exchange ratio (RER), profile of mood states (POMS), and dietary intake were assessed. Results: Twenty-seven women and twenty men completed the 12-week intervention. No differences at baseline existed between groups (AM vs PM) for both women and men cohorts. In women, significant interactions (p < 0.05) existed for 1RM bench (8 ± 2 vs 12 ± 2, ∆kg), pushups (9 ± 1 vs 13 ± 2, ∆reps), BT (10 ± 6 vs 45 ± 28, ∆watts), SJ (135 ± 6 vs 39 ± 8, ∆watts), fat mass (−1.0 ± 0.2 vs −0.3 ± 0.2, ∆kg), Abfat (−2.6 ± 0.3 vs −0.9 ± 0.5, ∆kg), diastolic (−10 ± 1 vs−5 ± 5, ∆mmHg) and systolic (−12.5 ± 2.7 vs 2.3 ± 3, mmHg) BP, AM vs PM, respectively. In men, significant interactions (p < 0.05) existed for systolic BP (−3.5 ± 2.6 vs −14.9 ± 5.1, ∆mmHg), RER (−0.01 ± 0.01 vs −0.06 ± 0.01, ∆VCO2/VO2), and fatigue (−0.8 ± 2 vs −5.9 ± 2, ∆mm), AM vs PM, respectively. Macronutrient intake was similar among AM and PM groups. Conclusion: Morning exercise (AM) reduced abdominal fat and blood pressure and evening exercise (PM) enhanced muscular performance in the women cohort. In the men cohort, PM increased fat oxidation and reduced systolic BP and fatigue. Thus, ETOD may be important to optimize individual exercise-induced health and performance outcomes in physically active individuals and may be independent of macronutrient intake.