Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate.
Ontology highlight
ABSTRACT: Objective
The Before School Functioning Questionnaire and Parent Rating of Evening and Morning Behavior-Revised assess early morning (BSFQ, PREMB-R AM subscale) and late afternoon/evening (PREMB-R PM subscale) functional impairment in children with ADHD. Clinically meaningful improvements were identified and applied to a trial of delayed-release and extended-release methylphenidate (DR/ER-MPH) in children with ADHD (NCT02520388) to determine if the statistically-determined improvements in functional impairment were also clinically meaningful.Method
Clinically meaningful improvements in BSFQ/PREMB-R were established post hoc by receiver operating characteristics curves, using anchors of Clinical Global Impression-Improvement (CGI-I) = 1 and CGI-I ≤ 2. Percentages of participants achieving these thresholds were calculated.Results
Thresholds for CGI-I = 1/CGI-I ≤ 2, respectively, were 27/20 (BSFQ), 5/3 (PREMB-R AM), and 9/5 (PREMB-R PM)-point decreases. More children achieved clinically meaningful improvements with DR/ER-MPH versus placebo (all p < .05).Conclusion
DR/ER-MPH increased proportions of children achieving clinically meaningful improvements in BSFQ and PREMB-R.
SUBMITTER: Wilens TE
PROVIDER: S-EPMC8785267 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Study objectivesShift sleep onset earlier and extend school-night sleep duration of adolescents.MethodsForty-six adolescents (14.5-17.9 years; 24 females) with habitual short sleep (≤7 h) and late bedtimes (≥23:00) on school nights slept as usual for 2 weeks (baseline). Then, there were three weekends and two sets of five weekdays in between. Circadian phase (Dim Light Melatonin Onset, DLMO) was measured in the laboratory on the first and third weekend. On weekdays, the "Intervention" group gradually advanced school-night bedtime (1 h earlier than baseline during week 1; 2 h earlier than baseline during week 2). Individualized evening time management plans ("Sleep RouTeen") were developed to facilitate earlier bedtimes. On the second weekend, Intervention participants received bright light (~6000 lux; 2.5 h) on both mornings. A control group completed the first and third weekend but not the second. They slept as usual and had no evening time management plan. Weekday sleep onset time and duration were derived from actigraphy.ResultsDim light melatonin onset (DLMO) advanced more in the Intervention (0.6 ± 0.8 h) compared to the Control (-0.1 ± 0.8 h) group. By week 2, the Intervention group fell asleep 1.5 ± 0.7 h earlier and sleep duration increased by 1.2 ± 0.7 h; sleep did not systematically change in the Control group.ConclusionsThis multi-pronged circadian-based intervention effectively increased school-night sleep duration for adolescents reporting chronic sleep restriction. Adolescents with early circadian phases may only need a time management plan, whereas those with later phases probably need both time management and morning bright light.Clinical trialsTeen School-Night Sleep Extension: An Intervention Targeting the Circadian System (#NCT04087603): https://clinicaltrials.gov/ct2/show/NCT04087603.
| S-EPMC9832518 | biostudies-literature
Project description: Not available
| S-EPMC8869321 | biostudies-literature
Project description: Not available
| S-EPMC8092481 | biostudies-literature
Project description:To assess morning stiffness in rheumatoid arthritis (RA) patients switched from immediate-release (IR) to delayed-release (DR) prednisone.Circadian Administration of Prednisone in Rheumatoid Arthritis-1 (CAPRA-1) is a 12-week, randomized, multicentre, active-controlled study of morning stiffness that consisted of a double-blind phase and a 9-month open-label extension. Patients receiving IR prednisone with no significant improvement after the double-blind study were switched to DR prednisone. Morning stiffness duration and median absolute and relative changes in pain and global assessment were evaluated (3, 6, and 9 months).In patients switched from IR to DR prednisone (n=110), statistically significant reductions in morning stiffness occurred over 3 months and were sustained for 9 months. Absolute reduction of morning stiffness was ~50 min with >40% relative reduction at each visit. Interleukin (IL)-6 levels were reduced by the same amount. Statistically significant and clinically meaningful mean reductions in morning stiffness were maintained at >67 min at each visit along with significant improvements in pain and patient global assessment. There was no evidence of tachyphylaxis seen over the 9-month study.Patients receiving disease-modifying anti-rheumatic drugs (DMARDs) and IR prednisone who had not had significant reductions in morning stiffness demonstrated statistically significant and clinically meaningful improvements when switched to DR prednisone.
| S-EPMC4732433 | biostudies-literature
Project description:From among physiological attributes commonly targeted in rehabilitation, to identify those in which changes led to clinically meaningful differences (CMDs) in mobility outcomes.Secondary analysis of data collected for a randomized controlled trial of exercise using binary outcomes defined by recording a large CMD (Short Physical Performance Battery (SPPB)=1 unit; gait speed (GS)=0.1 m/s). Iterative models were performed to evaluate possible confounding between physiological variables and relevant covariates.Outpatient rehabilitation centers.Community-dwelling mobility-limited older adults (n=116) participating in a 16-week randomized controlled trial of two modes of exercise.Physiological measures included leg power, leg strength, balance as measured according to the Performance-Oriented Mobility Assessment (POMA), and rate pressure product at the maximal stage of an exercise tolerance test. Outcomes included GS and SPPB. Leg power and leg strength were measured using computerized pneumatic strength training equipment and recorded in Watts and Newtons, respectively.Participants were 68% female, had a mean age of 75.2, a mean of 5.5 chronic conditions, and a baseline mean SPPB score of 8.7. After controlling for age, site, group assignment, and baseline outcome values, leg power was the only attribute in which changes were significantly associated with a large CMD in SPPB (odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02) and GS (OR=1.31, 95% CI=1.01-1.70).Improvements in leg power, independent of strength, appear to make an important contribution to clinically meaningful improvements in SPPB and GS.
| S-EPMC3051803 | biostudies-literature
Project description:BackgroundGait impairment is common in multiple sclerosis (MS) and negatively impacts patients' health-related quality of life (HRQoL). Prolonged-release fampridine (PR-fam) improves walking speed, but it is unclear which walking measures are the most suitable for identifying treatment response. Our aim was to assess the effect of PR-fam and the outcome measures that best identify short- and long-term clinically meaningful response.MethodsWe conducted a prospective study in 32 MS patients treated with PR-fam for a year. The assessments at 2 weeks, 3, 6 and 12 months included: timed 25-foot walk (T25FW), 6-minute walk test (6MWT), MS Walking Scale-12 (MSWS-12), a five-level version of the EuroQoL-5 dimensions, and accelerometry. PR-fam response was defined as an improvement in T25FW ?20%.ResultsTwenty-five (78%) patients were considered responders after 2 weeks of PR-fam and improved significantly in all measures. Responders to T25FW and MSWS-12 (n = 19) showed a significant improvement in HRQoL and accelerometer data compared with responders only to T25FW (n = 6). At 1 year, 15/20 (75%) patients remained responders, but only those with permanent response to T25FW and MSWS-12 (n = 8; 53%) showed a significant improvement in 6MWT and HRQoL.ConclusionThe combination of T25FW and MSWS-12 identify better those patients with a clinically significant benefit of PR-fam.
| S-EPMC6024337 | biostudies-literature
Project description:Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint score of less than or equal to 18 on the ADHD-RS-IV (or a mean score of 1). Responders have been defined as patients who achieve a CGI-I score of much or very much improved (1 or 2). There is a lack of agreement in the literature on what percent change in symptoms on the ADHD-RS-IV should be used to define improvement or remission. This study uses data from a clinical trial of a methylphenidate extended release (MPH-MLR; Aptensio XR®) phase III clinical trial to attempt to determine the percent change of symptoms that best corresponds with improvement and remission. Symptom remission at endpoint (ADHD-RS-IV total score ≤18) was most closely aligned with a ≥46% reduction in ADHD-RS-IV total score. Clinical improvement was most closely aligned with a ≥40% reduction in ADHD-RS-IV total score. The three different measures of outcome were strongly aligned during double blind and open label treatment, and were independent of subtype status. Our data suggest that at least 40% improvement in symptoms is needed to achieve a robust response at endpoint.
| S-EPMC6517933 | biostudies-literature
Project description:Objective:To determine the time to first clinically meaningful improvement in best-corrected visual acuity (BCVA) in patients treated with ranibizumab for diabetic macular oedema (DME) and identify predictors of early visual improvement. Methods and analysis:We retrospectively analysed the phase III RIDE (NCT00473382) and RISE (NCT00473330) trials, in which 759 patients with DME were randomised to monthly intravitreal ranibizumab 0.3?mg (n=250), ranibizumab 0.5?mg (n=252) or sham treatment (n=257). After month 24, 191 sham-treated patients crossed over to monthly ranibizumab 0.5?mg through month 36, while ranibizumab-treated patients continued treatment. Kaplan-Meier analyses assessed time to achieve ?15?or ?10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter gains from baseline or ?20/40 Snellen equivalent BCVA in each treatment arm. Baseline predictors of ?15 ETDRS letter gains at month 6 were identified by logistic regression. Results:Median time to first ?15 ETDRS letter gain was significantly shorter in patients who received ranibizumab (0.3?mg, 11.1 months; 0.5?mg, 10.9 months) than sham-treated patients who crossed over to ranibizumab 0.5?mg at month 24 (35.7 months; both p<0.0001). Half of ranibizumab-treated patients achieved ?20/40 BCVA within 2.3 (0.3 mg) and 1.9 months (0.5?mg). Baseline predictors of early vision improvement among ranibizumab-treated patients were BCVA ?55 ETDRS letters, younger age and presence of subretinal fluid. Conclusion:Prompt ranibizumab therapy for DME was associated with rapid, clinically meaningful vision gains that were maintained over 36 months of treatment. Lower BCVA, younger age and presence of subretinal fluid were predictive of early vision improvement.
| S-EPMC6830470 | biostudies-literature
Project description:Binge alcohol consumption elicits acute and robust increases of muscle sympathetic nerve activity (MSNA), yet the impact of evening binge drinking on morning-after MSNA is unknown. The present study examined the effects of evening binge alcohol consumption on polysomnographic sleep and morning-after MSNA. We hypothesized that evening binge drinking (i.e. 4-5 drink equivalent in <2 h) would reduce sleep quality and increase morning-after blood pressure (BP) and MSNA. Following a familiarization night within the sleep laboratory, 22 participants (12 men, 10 women; 25 ± 1 yr) were examined after simulated binge drinking or fluid control (randomized, crossover design). Morning MSNA was successfully recorded across both conditions in 16 participants (8 men, 8 women) during a 10-min baseline and three Valsalva's maneuvers (VM). Binge drinking reduced rapid eye movement (REM) sleep (15 ± 1 vs. 20 ± 1%, P = 0.003), increased stage II sleep (54 ± 1 vs. 51 ± 1%, P = 0.002), and increased total urine output (2.9 ± 0.2 vs. 2.1 ± 0.1 liters, P < 0.001) but did not alter morning-after urine specific gravity. Binge drinking increased morning-after heart rate [65 (54-72) vs. 58 (51-67) beats/min, P = 0.013] but not resting BP or MSNA. Binge drinking elicited greater sympathoexcitation during VM (38 ± 3 vs. 43 ± 3 bursts/min, P = 0.036). Binge drinking augmented heart rate (P = 0.002), systolic BP (P = 0.022), and diastolic BP (P = 0.037) reactivity to VM phase IV and blunted cardiovagal baroreflex sensitivity during VM phases II (P = 0.028) and IV (P = 0.043). In conclusion, evening binge alcohol consumption disrupted REM sleep and morning-after autonomic function. These findings provide new mechanistic insight into the potential role of binge drinking on cardiovascular risk.NEW & NOTEWORTHY Chronic binge alcohol consumption is associated with future cardiovascular disease (CVD) risk in both men and women. In addition, binge alcohol consumption is known to disrupt normal sleep quality during the early morning hours, coinciding with the morning sympathetic surge. In the present study, an evening of binge alcohol consumption increased baseline morning heart rate and cardiovascular reactivity during the Valsalva maneuver (VM) strain. Specifically, muscle sympathetic nerve activity and phase IV hemodynamic responses increased during VM the morning after binge alcohol consumption. The autonomic dysfunction and increased cardiovascular reactivity during VM suggests a contributing mechanism to CVD risk present in individuals who binge drink.
| S-EPMC7864252 | biostudies-literature
Project description:BackgroundVariation in blood pressure levels display circadian rhythms. The morning surge in blood pressure is known to increase the risk of myocardial events in the first several hours post awakening. A systematic review of the administration-time-related-effects of evening versus morning dosing regimen of antihypertensive drugs in the management of patients with primary hypertension has not been conducted.ObjectivesTo evaluate the administration-time-related-effects of antihypertensive drugs administered as once daily monotherapy in the evening versus morning administration regimen on all cause mortality, cardiovascular morbidity and reduction of blood pressure in patients with primary hypertension.Search strategyWe searched Cochrane CENTRAL on Ovid (4th Quarter 2009), Ovid MEDLINE (1950 to October 2009), EMBASE (1974 to October 2009), the Chinese Biomedical literature database (1978 to 2009) and the reference lists of relevant articles. No language restrictions were applied.Selection criteriaRandomized controlled trials comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in patients with primary hypertension were included. Patients with known secondary hypertension, shift workers or white coat hypertension were excluded.Data collection and analysisTwo authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Data synthesis and analysis were done using RevMan 5.1. Random effects meta-analysis and sensitivity analysis were conducted.Main results21 randomized controlled trials (RCTs) in 1,993 patients with primary hypertension met the inclusion criteria for this review - ACEIs (5 trials), CCBs (7 trials), ARBs (6 trials), diuretics (2 trials), alpha-blockers (1 trial), and beta-blockers (1 trial). Meta-analysis showed significant heterogeneity across trials.No RCT reported on all cause mortality, cardiovascular mortality, cardiovascular morbidity and serious adverse events.There was no statistically significant difference for overall adverse events (RR=0.78, 95%CI: 0.37 to 1.65) and withdrawals due to adverse events (RR=0.53, 95%CI: 0.26 to 1.07).No significant differences were noted for morning SBP (-1.62 mm Hg, 95% CI: -4.19 to 0.95) and morning DBP (-1.21 mm Hg, 95% CI: -3.28 to 0.86); but 24-hour BP (SBP: -1.71 mm Hg, 95% CI: -2.78 to -0.65; DBP: -1.38 mm Hg, 95% CI: -2.13 to -0.62) showed a statistically significant difference.Authors' conclusionsNo RCT reported on clinically relevant outcome measures - all cause mortality, cardiovascular morbidity and morbidity. There were no significant differences in overall adverse events and withdrawals due to adverse events among the evening versus morning dosing regimens. In terms of BP lowering efficacy, for 24-hour SBP and DBP, the data suggests that better blood pressure control was achieved with bedtime dosing than morning administration of antihypertensive medication, the clinical significance of which is not known.
| S-EPMC9040377 | biostudies-literature