Baseline Standard Deviation Research Articles

Effectiveness of Group Physical Exercise in Treating Major Depressive Disorder: An Analysis of Secondary Data from an Aborted Randomized Trial.

Depression is highly prevalent and a significant cause of mortality and morbidity across the globe. Although antidepressants and/or psychotherapy are often used to treat depression, some recent studies indicate that exercise may play an important role in lowering depression symptoms among patients meeting the clinical criteria of a depressive episode. This study aimed to evaluate the mental health and wellbeing of adult participants diagnosed with major depressive disorder (MDD) after fourteen weeks of receiving a supervised physical exercise program. In a pre-post design, the assessments were performed at baseline, seven weeks and fourteen weeks following the exercise intervention program using facilitated self-reported psychometric scales. The Beck Depression Inventory (BDI-2) and Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) were used to assess depression. The short form of the International Physical Activity Questionnaire (IPAQ) was used for the self-reporting of participants' physical activity. At the beginning of the study, the baseline total mean scores and standard deviations for the BDI-2, CORE-OM, and IPAQ in both genders did not differ significantly (p-value > 0.05). Patients showed significant improvement in all assessment scales after completing fourteen weeks of the physical exercise program. Based on the BDI-2, the baseline score dropped from 31.25 (indicating moderate to severe depression) to 14.25 (indicating mild to minimal depression), with a p-value of <0.001. The CORE-OM total mean score was reduced from 1.91 to 0.98 with a significant p-value < 0.005 indicating effective clinical improvement in depression symptoms. The IPAQ total MET-minutes/week mean score increased from 1713.22 to 4367.62, indicating an improvement in the participants' weekly P.E. intake; however, the change was not statistically significant (p = 0.07). Exercise treatment is linked with considerable therapeutic improvement in patients with MDD, particularly when exercise is sustained over time. The BDI-2 and CORE-OM total scores significantly decreased after the fourteen-week P.E. programme, indicating a change from moderate and severe depression to minimal and mild depression. Our findings offer insightful information to primary care doctors and psychiatrists, indicating that prescribing exercise to depressed patients may be a helpful adjunctive therapy.

Cognitive Behaviour Therapy for Depersonalisation Derealisation Disorder (CBT-f-DDD): Study protocol for a randomised controlled feasibility trial.

Depersonalisation-Derealisation Disorder (DDD) is a distressing mental health condition which causes individuals to have a sense of 'unreality' or detachment about themselves and/or the world around them. DDD is chronically under-researched, and as a result, under-diagnosed, with a population prevalence of about 1%. In systematic reviews, Cognitive Behavioural Therapy (CBT) has been found to be the only intervention with significant clinical impact on alleviating the symptoms of DDD. However, previous studies have suffered from small sample sizes, reliance on expert clinicians to provide therapy and narrow population demographics. This feasibility randomised controlled trial aims to provide more robust evidence for the treatment efficacy of CBT in DDD. The study aims to recruit 40 participants from two NHS trusts, 20 per arm from two community Mental Health NHS services in London. The intervention group will receive 12-24 individual CBT sessions over a 6-month period from CBT therapists following specialist training for DDD. The control group will receive Treatment as Usual. We will assess the feasibility of a future RCT through measuring the acceptability of the intervention, and assessing our ability to recruit, retain and randomise participants. We will calculate the correlation of scores on the Cambridge Depersonalisation Scale, its baseline standard deviation, assess the magnitude/direction of change and characterise the uncertainty in the outcome scores and the probability that the results have been obtained by chance. The outputs of this trial will guide whether a definite RCT is feasible and acceptable, for both the clinician and participant. The ISRCTN registration number is ISRCTN97686121(https://doi.org/10.1186/ISRCTN97686121).

Effect of Plyometrics on Bone Mineral Density in Young Adults: A Systematic Review and Meta-Analysis

ABSTRACT Context Osteoporosis is a chronic bone metabolic disease characterized by decreased bone mass, leading to increased frailty and a subsequent fracture risk. Peak bone mineral density (BMD) is achieved in early adulthood and may be the most important factor leading to the development of osteoporosis in older adults. Objective This study aimed to analyze the effects of plyometrics on BMD in young men and premenopausal women. Design This study used randomized controlled trials found in MEDLINE, Embase, and CINAHL published between January 1, 1990, and November 1, 2022. Keywords included plyometrics, jumping, jump training, bone health, and bone mineral density. Articles were assessed for methodological quality using the Consolidated Standards of Reporting Trials 2010 checklist. Eligibility Criteria Randomized controlled trials investigating BMD in healthy premenopausal women and men between the ages of 18 and 60 yr that compared plyometrics with control were included. Study Selection Two reviewers independently screened 553 abstracts. Main Outcome Measures Mean baseline and follow-up dual-energy x-ray absorptiometry scores and standard deviations were extracted to calculate the standard mean difference. After extraction, the magnitude of difference between control and treatment groups were analyzed using the Hedges and Olkin method for effect size. Results The 12 included studies had high methodological quality. Of the 12 studies, 10 reported statistically significant increase in BMD at ≥1 site when compared with control. Two studies showed equal improvement when compared with resistance-only training. After analysis, a large positive effect size with strongly positive correlation was seen between plyometrics and lumbar spine BMD. Conclusion Plyometric training is a safe and time-efficient method to improve BMD in premenopausal people 18–65 yr old. Large effect sizes were associated with increased training intensity and lasted months after the intervention was complete. Plyometrics seems to be a comparable alternative to resistance training with respect to bone health.

Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy.

Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5±7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size=1.6, standard error of measurement=2.5, ½ baseline standard deviation=4.0, and minimal detectable change=6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3±5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p<0.04). The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.

Xanamem shows pro‐cognitive activity with clinically meaningful effect sizes across 3 independent, placebo‐controlled clinical trials

AbstractBackgroundXanamem® is a brain‐penetrant inhibitor of 11‐beta hydroxysteroid dehydrogenase type 1, which converts intracellular cortisone to cortisol and is highly expressed in brain regions such as the hippocampus. Elevated plasma and CSF cortisol is strongly associated with cognitive decline.MethodEffects of Xanamem on cognition were assessed in 3 independent, placebo‐controlled, double‐blind trials. The XanaHES (n = 42, 20 mg) and XanaMIA (n = 105, 5 &amp; 10 mg) Phase 1b trials used the computerised Cogstate system to assess cognition in normal, older volunteers. The XanADu‐X biomarker extension study (n = 72, 10 mg) explored clinical and cognitive outcomes in subgroups (n = 34 each) of the XanADu Phase 2a AD trial with higher (H) or lower (L) plasma p‐Tau181 in a new prospective analysis. To compare the results across trials, we focus on the cognitive effect sizes measured by the Cohen’s statistic (treatment effect vs. placebo / pooled baseline standard deviation).ResultXanamem was safe and well‐tolerated with no treatment‐related SAEs and the predominantly mild AEs were generally equally distributed between Xanamem and placebo. In XanaHES and XanaMIA, a pattern of clinically significant improvements was observed in attention and working memory compared to placebo in the Xanamem groups, with Cohen’s d ranging up to 1.27. Improvements from baseline were observed in both Xanamem and placebo in domains of episodic memory and executive function without a treatment difference. In XanADu, Xanamem demonstrated clinically significant benefit with a Cohen’s d of 0.41 on the CDR‐SB compared to placebo in the H group but not in the L group. In both L and H groups improvements in executive function were seen favouring Xanamem (Cohen’s d = 0.34 and 0.26, respectively) and the MMSE (Cohen’s d = 0.32 and 0.16, respectively). There were no improvements observed on original XanADu primary outcome measures of ADAS‐Cog14 and ADCOMs.ConclusionXanamem displays activity in multiple domains of cognition including attention, working memory, and executive function with clinically meaningful effects in normal subjects and in patients with p‐Tau‐elevated mild AD. These data suggest Xanamem may be both a pro‐cognitive drug and disease‐modifying agent and guide design of future trials.

Association of intraoperative cerebral and somatic tissue oxygen saturation with postoperative acute kidney injury in adult patients undergoing multiple valve surgery

BackgroundThe association between tissue oxygenation with postoperative acute kidney injury (AKI) in adult patients undergoing multiple valve surgery has not been specifically studied.MethodsIn this prospective exploratory cohort study, 99 patients were enrolled. The left forehead, the left forearm, the left upper thigh, and the left renal region tissue oxygen saturation using near-infrared spectroscopy were monitored. The association between each threshold and AKI was assessed. The relative and absolute thresholds were < 70%, < 75%, < 80%, < 85%, < 90%, < 95%, and < 100% baseline, and baseline-standard deviation (SD), -1.5 SD, -2 SD, -2.5 SD, and -3 SD. Multivariate logistic regression analysis was adopted to explore the association.ResultsAKI occurred in 53 (54%) patients. The absolute value-based SrrO2 thresholds associated with AKI were baseline-3 SD (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.238–17.314; P = 0.023) and baseline-2.5 SD (OR, 2.842; 95% CI, 1.025–7.881; P = 0.045) after adjusting for the potential confounders, those are renal region tissue oxygen saturation of 55% and 60%, but not statistically significant after correcting for multiple testing (corrected P = 0.114 and 0.179, respectively).ConclusionThe SrrO2 desaturation, defined as < baseline – 2.5 SD or < baseline – 3 SD, may be associated with AKI. The thresholds need to be verified in future large-scale studies.Trial registrationsThe study was registered at ClinicalTrials.gov, first trial registration: 26/10/2017, identifier: NCT03323203.

Test-retest repeatability for Fatigue Assessment Scale, Short-Form 6-Dimension and King's Sarcoidosis Questionnaire in people with sarcoidosis associated fatigue.

Patient related outcomes are important in sarcoidosis but the medium-term repeatability of the key patient reported outcome measure is not known. We aimed to test the repeatability of the Fatigue Assessment Scale (FAS), Short Form 6-Dimension (SF-6D), and King's Sarcoidosis Questionnaire (KSQ) in free living people with sarcoidosis associated fatigue. Twelve people with sarcoidosis associated fatigue completed the FAS, short form 36 questionnaire (SF-36) and the KSQ at baseline and 12 weeks. The SF-6D utility was calculated from the SF-36. The difference between baseline and 12 week assessments was measured. The interclass correlation (95% confidence interval) showed good agreement between the baseline and 3 months measurements: FAS 0.91 (0.74, 0.71), SF-36 0.98 (0.94, 1), KSQ 0.98 (0.93, 0.99), SF-6D utility 0.98 (0.93, 0.99). The baseline (standard deviation) FAS was 27.83 (5.86) and at 12 weeks was 27.25 (7.55) representing 0.58 difference (95% CI for difference (-1.89, 3.06)), SF-6D utility was 0.69 (0.16) at baseline and 0.68 (0.17) after 3 months representing at 0.00 (-0.03, 0.03) difference and corresponding values for KSQ were 59.12 (18.68) and 56.91 (27.26) with a difference of -1.87 (5.49,1.76). There was good repeatability of FAS, SF-36, SF-6D and KSQ in free living people with sarcoidosis associated fatigue. Fatigue, general and disease specific health related quality of life showed no significant change over a 12 week period. Studies identifying changes in these outcomes can confidently report a true change and not measurement error or regression to the mean.

Poor oral health predicts cognitive impairment in elders

AbstractBackgroundTooth loss, periodontal disease, dementia, and Alzheimer’s disease share several risk factors in older adults. Several previous studies have reported positive associations between these dental problems and global cognitive defects. However, limited is known about the relationships among multiple dental/periodontal statuses and different cognitive domains.MethodThis six‐year (2011‐2017) cohort study includes 515 older adults (65+). Global cognition was assessed by Montreal cognitive assessment‐Taiwan version (MoCA‐T). For cognitive domains, we used logical memory tests (immediate and delayed theme and free recall) in Wechsler Memory Scale‐Third Edition (WMS‐III) to assess memory. Trail Making Test A and B was used to assess attention and executive function, respectively. Digit span‐forward and backward was used to evaluate attention and working memory/short‐term memory, respectively. Verbal fluency tests were used to assess category/semantic fluency. A Z‐score was calculated for each cognitive domain‐specific test according to baseline mean and standard deviation. Oral health status includes tooth defect (dental caries, tooth wear, cervical abrasion, retained root or crown fracture), periodontal health (disease severity from healthy periodontal status, gingivitis to periodontitis), and arch integrity (no tooth loss nor retained root or crown fracture). Generalized linear mixed models were used to assess the associations above adjust important covariates.ResultAt baseline, periodontitis was associated with poor performance in executive function [Trail Making Test A: b = ‐0.14, 95% confidence interval (CI) = ‐0.27 to ‐0.01]. The association between baseline severity of tooth defect and poor memory decreased (logical memory‐immediate theme recall: b = ‐0.05, 95% CI = ‐0.10 to ‐0.01); similarly finding was found for attention domain (digit span‐forward: b = ‐0.04, 95% CI = ‐0.07 to ‐0.001). At baseline, loss of arch integrity was associated with a better working memory/short‐term memory (digit span‐backward: β = 0.18, 95% CI = 0.01 to 0.36); as follow‐up time increased, this association decreased over six years (β = ‐0.04, 95% CI = ‐0.07 to ‐0.003).ConclusionPeriodontitis, tooth defects, or arch integrity was associated with poor performance of cognitive domains (memory, attention, and executive function) over time. A oral health evaluation may serve as predictors of the preclinical phase of dementia in its upcoming years.

A statistical algorithm for outbreak detection in multisite settings: an application to sick leave monitoring.

Public health authorities monitor cases of health-related problems over time using surveillance algorithms that detect unusually high increases in the number of cases, namely aberrations. Statistical aberrations signal outbreaks when further investigation reveals epidemiological significance. The increasing availability and diversity of epidemiological data and the most recent epidemic threats call for more accurate surveillance algorithms that not just detect aberration times but also detect locations. Sick leave data, for instance, can be monitored across companies to identify companies-related aberrations. In this context, we develop an extension to multisite surveillance of a routinely used aberration detection algorithm, the quasi-Poisson regression Farrington Flexible algorithm. The new algorithm consists of a negative-binomial mixed effects regression model with a random effects term for sites and a new reweighting procedure reducing the effect of past aberrations. A wide range of simulations shows that, compared with Farrington Flexible, the new algorithm produces better false positive rates and similar probabilities of detecting genuine outbreaks, for case counts that exceed historical baselines by 3SD. As expected, higher surges lead to lower false positive rates and higher probabilities of detecting true outbreaks. The new algorithm provides better detection of true outbreaks, reaching 100%, when cases exceed eight baseline standard deviations. We apply our algorithm to sick leave rates in the context of COVID-19 and find that it detects the pandemic effect. The new algorithm is easily implementable over a range of contrasting data scenarios, providing good overall performance and new perspectives for multisite surveillance. All the analyses are performed in the R statistical software using the package glmmTMB. The code for performing the analyses and for generating the simulations can be found online at the following link: https://github.com/TomDuchemin/mixed_surveillance. a.noufaily@warwick.ac.uk.

Sugar-sweetened beverage intakes and age of menarche in Chinese girls in 2004-2015

To investigate the prospective association between sugar-sweetened beverage intakes and age at menarche among Chinese girls. Based on China Health and Nutrition Survey(CHNS) from 2004 to 2015, 293 girls aged 7-16 years with both data on sugar-sweetened beverage intake 1-5 years before menarche and age of menarche were included in the present study. Multivariate linear regression analysis and Logistic regression analysis were used to explore the influence of the sugar-sweetened beverage consumption on menarcheal age of Chinese girls. The median age at menarche of girls was 12 years old. The consumption of sugar-sweetened beverages(SSBs) was 0.5(0.2, 1.0) L/week for sweetened soft drinks, 0.5(0.2, 0.9) L/week for sweetened fruit drinks and 0.6(0.3, 1.3) L/week for total. After adjusting age at baseline, residency, maternal educational, level, energy intake at baseline and body mass index standard deviation score, no significant association was found between sweetened soft drinks, sweetened fruit drinks, total sugar-sweetened beverage intake and age at menarche. The intake of sugary beverages may not be prospectively related to the age of menarche among Chinese girls.

Electrocardiogram Belt guidance for left ventricular lead placement and biventricular pacing optimization

Patients with ischemic cardiomyopathy, non-left bundle branch block, or QRS duration <150 ms have a lower response rate to cardiac resynchronization therapy (CRT) than did other indicated patients. The ECG Belt system (EBS) is a novel surface mapping system designed to measure electrical dyssynchrony via the standard deviation of the activation times of the left ventricle. The objectives of this study were to evaluate the efficacy of the EBS in patients less likely to respond to CRT and to determine whether EBS use in lead placement guidance and device programming was superior to standard CRT care. This was a prospective randomized trial of patients with heart failure and EBS-guided CRT implantation and programming vs standard CRT care. The primary end point was relative change in left ventricular end-systolic volume from baseline to 6 months postimplantation. A total of 408 patients from centers in Europe and North America were randomized. Although both patients with EBS and control patients had a mean improvement in left ventricular end-systolic volume, there was no significant difference in relative change from baseline (P = .26). While patients with a higher baseline standard deviation of the activation times derived greater left ventricular reverse remodeling, improvement in electrical dyssynchrony did not correlate with the extent of reverse remodeling. The findings of the present study do not support EBS-guided therapy for CRT management of heart failure with reduced ejection fraction.

32240 Baseline characteristics and comorbid conditions in patients with moderate-to-severe plaque psoriasis enrolled in the Psoriasis Study of Health Outcomes (PSoHO)

Aim: This interim analysis of the Psoriasis Study of Health Outcomes (PSoHO) describes the baseline comorbidities of the first 700 enrolled patients to improve our understanding of treatment patterns in the real-world setting. Methods: PSoHO is a 3-year international, prospective, multicenter, noninterventional cohort study comparing the clinical effectiveness of antiinterleukin (IL)-17A biologics versus other biologics in treating PsO. Patients (≥18 years) had moderate-to-severe PsO and initiated/switched biologics during routine medical care. Physicians recorded patients’ baseline comorbidities from a prespecified list. Baseline comorbidity rates by treatment group were analyzed using Fisher exact test. Results: This interim cohort (n = 700) was 57.7% male, with a mean baseline (standard deviation) age of 46.2 (13.7) years, Body Mass Index of 29.5 (6.9), Psoriasis Area and Severity Index of 14.8 (8.6) and Dermatology Life Quality Index of 11.9 (7.5). The mean number of comorbidities was 1.3 (1.8) with 59.2% (181/306) of the anti-IL-17A cohort and 59.4% (234/394) of the other biologics cohort reporting comorbidities. For the anti-IL-17A and other biologics cohorts, the most frequent comorbidities were psoriatic arthritis (25.2% [77/306] and 19.5% [77/394]), hypertension (25.5% [78/306] and 25.1% [99/394]), dyslipidemia (19.3% [59/306] and 17.0% [67/394]) and diabetes (8.8% [27/306] and 10.7% [42/394]), respectively. No significant differences were observed between cohorts for all reported comorbidities. Conclusion: This interim analysis suggests that biologic-treated patients with PsO have more heterogenous disease and a higher comorbid disease burden in the real world than clinical trial populations, including conditions that usually exclude clinical trial enrollment.

Evaluating Social Connection and Well-being in an Intergenerational Telephone Visit Program during the COVID pandemic: A Pilot Study

IntroductionPublic health recommendations during COVID-19 have resulted in greater objective social isolation among older adults, putting them at risk for loneliness, depression and worsening of age-related morbidities such as cognitive impairment and cardiovascular disease. During the pandemic, volunteer organizations, such as the Concordium Program at Harvard College, have offered friendly telephone visits to older adults in the community to relieve feelings of loneliness and to promote emotional well-being, though the acceptability and efficacy of these interventions have not been well-established. This study evaluated the methods and participant experience of a remotely-delivered intergenerational, telephone intervention for older adults living alone during the COVID-19 pandemic and assessed measures of socioemotional well-being before, during, and after the intervention.MethodsWe recruited nine community-dwelling adults who lived alone and endorsed loneliness through a research registry and clinic referrals. Individuals with hearing impairment were excluded. Nine undergraduates were recruited from the Harvard Concordium Program and were paired with an older adult participant based on mutual interests. Each dyad engaged in 8 weekly, 30 minute, unscripted telephone conversations. Each member of the pair answered online questionnaires at weeks 0 (pre), 4 (mid), and 8 (post) designed to assess loneliness (PROMIS Social Isolation Scale [PROMS]) and other aspects of psychological well-being (San Diego Wisdom Scale [SDW], Behavioral Activation for Depression Scale [BADS], Positive Affect and Well-Being Scale [PAWB], Perceived Stress Scale [PSS]). After completing all visits, older and younger adult participants responded to qualitative questions to evaluate the experience of the friendly visits through content analysis.ResultsFrom March to August 2021, 18 participants were enrolled, 9 of whom were older adults (mean age 74.53 [70-84], 88% women), 13 completed the study, and five dropped out.Among older adults who completed, numerical scores for loneliness, stress, and behavioral activation changed in an improved direction. Pre- and post-study mean scores and baseline standard deviation for older adults who completed are reported: PROMS (x¯=31.7, 27.7; sd=5.06), BADS (x¯=27.6, 35.1; sd=13.11) PAWB (x¯=33.4, 33.0; sd=5.51), PSS (x¯=14.4, 13.9; sd=4.35), SDW (x¯=83.6, 81.9; sd=4.72).ConclusionsPreliminary quantitative results point to possible improvements in loneliness, behavioral activation and perceived stress, though limited by low statistical power. Findings from this study will inform methods to optimize recruitment, improve implementation, and assess the effectiveness of friendly telephone visits to enhance social connection between younger and older adults in clinical and community settings.This research was funded byBrigham and Women's Hospital COVID Relief Fund

A Personalized, Telehealth Music Therapy Intervention for Lonely Older Adults: A Feasibility Study

<h3>Introduction</h3> Music listening interventions, facilitated by a qualified music therapist, have been shown to reduce late-life depression and anxiety but their impact on loneliness has not been well-studied. Risks associated with loneliness in older adults include depression, cognitive decline, poorer disease outcomes and premature mortality. This study evaluated the feasibility of a remotely-delivered, personalized music therapy intervention for older adults living alone during the COVID-19 pandemic, and assessed measures of socioemotional well-being before, during, and after the intervention. <h3>Methods</h3> We recruited community-dwelling cognitively unimpaired older adults who lived alone, endorsed loneliness and were able to use Zoom video conferencing. Individuals with cognitive impairment (TICS < 31), moderate-severe depression (GDS > 10), or hearing impairment were excluded. Eight weekly, individual music therapy sessions were conducted with a board-certified music therapist via Zoom to develop personalized music playlists and to learn specific music listening techniques. Participants listened to playlists for one hour daily, completed a daily journal, and answered online questionnaires at weeks 0 (pre), 4 (mid), and 8 (post). The primary outcome was the PROMIS Social Isolation Scale [PROMS] score. Other questionnaires included the Behavioral Activation for Depression Scale [BADS], Positive Affect and Well-Being Scale [PAWB], Perceived Stress Scale [PSS], Brief Symptom Inventory [BSI], and the Snaith-Hamilton Pleasure Scale [SHAPS]). Qualitative data were collected at week 8 for thematic analysis. <h3>Results</h3> From March to August 2021, 11 participants were enrolled (mean age 74.82 [66-85], 88% women), eight completed the study, and one dropped out, leaving two actively enrolled. Among those who completed, numerical scores for loneliness and all other outcomes changed in an improved direction. Pre- and post-study mean scores and baseline standard deviation for those who completed are reported: PROMS (x¯=20.0, 16.8; sd=5.88), BADS (x¯=36.3, 40.8; sd=10.48), PAWB (x¯=33.5, 37.1; sd=6.61), PSS (x¯=14.5, 11.6; sd=7.89), BSI (x¯=33.3, 23.5; sd=17.1), SHAPS (x¯=47.0, 50.62; sd=6.74). Qualitative interviews were notable for themes of joy and improvements in sleep, health, focus, and physical pain. Participants also reported increased connectedness to culture, country of origin, loved ones, and the music therapist. <h3>Conclusions</h3> Recruitment and participant acceptability of a virtual, personalized music therapy intervention have been positive. Interim data analysis points to a possible improvement in loneliness and other outcome measures, though limited by low statistical power. Music therapy appears to be a novel and feasible approach to address loneliness and emotional wellbeing in at-risk community-dwelling older adults.

The influence of manual therapy dosing on outcomes in patients with hip osteoarthritis: a systematic review

ABSTRACT Objective To 1) Determine if specific dosing parameters of manual therapy are related to improved pain, disability, and quality of life outcomes in patients with hip osteoarthritis and 2) to provide recommendations for optimal manual therapy dosing based on our findings. Design A systematic review of randomized controlled trials from the PubMed, CINAHL, and OVID databases that used manual therapy interventions to treat hip osteoarthritis was performed. Three reviewers assessed the risk of bias for included studies and extracted relevant outcome data based on predetermined criteria. Baseline and follow-up means and standard deviations for outcome measures were used to calculate effect sizes for within and between-group differences. Results Ten studies were included in the final analyses totaling 768 participants, and half were graded as high risk of bias. Trends emerged: 1) large effect sizes were seen using long-axis distraction, mobilization and thrust manipulation, 2) mobilization with movement showed large effects for pain and range of motion, and (3) small effects were associated with graded mobilization. Durations of 10 to 30 minutes per session, and frequency 2–3 times per week for 2–6 weeks were the most common dosing parameters. Conclusions There were varied effect sizes associated with pain, function, and quality of life for both thrust and non-thrust mobilizations, and mobilization with movement into hip flexion and internal rotation. Due to the heterogeneity of MT dosage, it is difficult to recommend a specific manual therapy dosage for those with hip osteoarthritis.

The impact of filgotinib on patient-reported outcomes and health-related quality of life for patients with active rheumatoid arthritis: a post hoc analysis of Phase 3 studies

BackgroundThe effects of filgotinib on patient-reported outcomes (PROs) from 3 trials in patients with active rheumatoid arthritis were investigated.MethodsMethotrexate (MTX)-naïve patients received filgotinib 200 or 100 mg plus MTX (FIL200+MTX, FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX monotherapy through 52 weeks (NCT02886728). Patients with inadequate response (IR) to MTX (MTX-IR) received FIL200+MTX, FIL100+MTX, adalimumab 40 mg +MTX (ADA+MTX), or placebo (PBO)+MTX (rerandomized to FIL200+MTX or FIL100+MTX at week 24) through 52 weeks (NCT02889796). Patients with IR to biologic disease-modifying antirheumatic drugs (bDMARD-IR) received FIL200 or FIL100 or PBO with background stable conventional synthetic (cs) DMARDs for up to 24 weeks (NCT02873936). PROs included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) physical/mental component summary (PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and Patient Global Assessment of Disease Activity (PtGA). Data are reported as least-squares mean changes from baseline with standard error to the timepoint representing each study’s primary endpoint. All statistical comparisons are of filgotinib groups vs their respective control groups.ResultsAt week 24, among MTX-naïve patients, change from baseline (standard deviation) in HAQ-DI was − 1.00 (0.03; P < 0.001) with FIL200+MTX, − 0.94 (0.04; P < 0.01) with FIL100+MTX, and − 0.91 (0.04; P < 0.05) with FIL200 alone compared with − 0.81 (0.03) with MTX alone. At week 12, among MTX-IR patients, change from baseline in HAQ-DI was − 0.69 (0.04; P < 0.001 vs PBO+MTX, P < 0.05 vs ADA) with FIL200+MTX, − 0.57 (0.04; P < 0.001 vs placebo) with FIL100+MTX, and − 0.60 (0.04) with ADA vs − 0.40 (0.04) with PBO+MTX. At week 12, among bDMARD-IR patients, change from baseline in HAQ-DI was − 0.50 (0.06; P < 0.001) with FIL200+csDMARD and − 0.46 (0.05; P < 0.001) with FIL100+csDMARD vs − 0.19 (0.06) with placebo+csDMARD. Changes in SF-36 PCS and MCS, FACIT-Fatigue, WPAI, and PtGA tended to favor filgotinib over PBO, MTX, and ADA. Greater proportions of patients experienced clinically meaningful differences with either dosage of FIL in combination with csDMARDs (including MTX) and with FIL200 monotherapy vs comparators.ConclusionsFilgotinib provided improvements in PROs across patient populations. These findings suggest filgotinib can be an effective treatment option for patients with insufficient response to MTX or bDMARDs and patients who are MTX-naïve.Trial registrationClinicalTrials.gov, FINCH 1, NCT02889796, first posted September 7, 2016; FINCH 2, NCT02873936, first posted August 22, 2016, retrospectively registered; FINCH 3, NCT02886728, first posted September 1, 2016, retrospectively registered.

OP0224 CONTINUOUS COMPOSITE MEASURES FOR ROUTINE CARE IN PSORIATIC ARTHRITIS: THRESHOLDS OF MEANING AND CLINICALLY IMPORTANT DIFFERENCE ESTIMATES FOR THE 3 AND 4 VAS SCALES FROM A UK MULTICENTRE STUDY

Background:There is a recognised need for a continuous composite measure of disease activity for the assessment of Psoriatic Arthritis (PsA) in routine clinical settings to allow objective assessment of response and implementation of treat to target.1 Longer multidimensional measures are considered less feasible in routine care and a number of shorter measures have been proposed including, the Disease Activity Score for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), the 3 Visual Analogue Scale (VAS) (comprising physician global VAS, patient global VAS and patient skin VAS) or 4 VAS (comprising physician global VAS, patient pain VAS, joint VAS and patient skin VAS). Testing of these measures in clinical trial datasets has been suggested but thresholds of meaning have not been established.2Objectives:To estimate clinically relevant thresholds of disease activity and improvement for composite measures for routine clinical practice in PsA.Methods:Clinical and patient reported outcome measures were assessed in patients fulfilling CASPAR criteria for PsA at three consecutive follow up visits in a UK multicentre observational study. Participants underwent clinical assessment and completed patient reported measures including health anchor questions. Estimates for Minimal Detectible Change (MDC) were derived using 1.96*2*Standard Error of the Mean (SEM). Minimal Clinically Important Difference (MCID) for improvement were derived using the health anchor method and two distribution methods (Table 1). Thresholds for low, moderate and high disease activity were triangulated from established cut-off values for the patient global VAS, PASDAS and DAPSA.Table 1.Minimal Clinically Important Difference (MCID) and Minimal detectable change (MDC)ANCHOR (MEDIAN)DISTRIBUTION#1DISTRIBUTION #2MDCCPDAI0.51.491.54.16GRACE0.260.60.772.18PASDAS1.220.640.761.58DAS280.20.850.621.463VAS1.131.160.913.124VAS1.110.960.942.45DAPSA7.259.0910.4035.63Disease Activity Score for Psoriatic Arthritis (DAPSA); Psoriatic Arthritis Disease Activity Score (PASDAS); Composite Psoriatic Arthritis Disease Activity Index (CPDAI); Disease Activity Score 28 (DAS28).Distribution #1: Baseline standard deviation (sd) * √ 1 – Cronbach’s alphaDistribution #2: 0.5 * baseline sdMinimal detectable change (MDC): 1.96*2*SEM where SEM = baseline sd √1 - ICCResults:139 subjects were recruited (59 male, 80 female, mean (range) age (years) 52.7 (19 – 83), mean (range) duration of psoriasis (years) 21.9 (2 – 71), mean (range) duration of psoriatic arthritis (years) 6.1 (0 – 41). Cut-off values for low, moderate and high disease activity were 1.3, 2.4, and 4.8 for the 3 Vas and 1.6, 2.8 and 5.0 for the 4 VAS (Figure 1). Estimates for the MCID and MDC for the continuous composite measures and are reported in Table 1.Conclusion:We report estimates of clinically relevant improvements for continuous composite measures in PsA and estimates of low, moderate and high disease activity for the 3 and 4 VAS scales. The thresholds of meaning can now be tested in independent observational and clinical trial datasets.

Trunk, Hip and Knee Exercise Programs for Pain Relief, Functional Performance and Muscle Strength in Patellofemoral Pain: Systematic Review and Meta-Analysis.

ObjectivePrevious research suggests that muscle strength exercise is the most effective rehabilitation methods in patients with patellofemoral pain (PFP). This systematic review with meta-analysis compared the effects of Hip&Knee, Hip-only and Knee-only exercise programs on pain relief, muscle strength, and functional performance in patients with PFP.MethodsLiterature searches of PubMed, PEDro and CINAHL databases revealed twenty-one studies included in the final descriptive review, thirteen of which were included in the meta-analysis. Data extraction included baseline and post-intervention means and standard deviations of all eligible outcome measures both for the intervention and control groups, participants baseline demographics and intervention characteristics.ResultsThe results showed that Hip&Knee and Hip-only exercise programs were comparatively effective, while the Knee-only exercise programs proved to be inferior to the above-mentioned approaches. The Hip&Knee exercise programs showed the greatest pain relief (mean difference = −1.71 (−3.11, −0.30); p = 0.02; I2 = 96%) and functional improvement (standardized mean difference = 1.28 (0.45, 2.12); p = 0.003; I2 = 84%), although the subgroup analysis did not show any significant difference compared to Hip-only exercise programs (p > 0.05).ConclusionOverall, Hip&Knee exercise programs appear to reduce pain and improve function more than other exercise programs and could be used as a primary rehabilitation approach in patients with PFP. However, the difference between the subgroups in most outcome measures suggests that Hip&Knee exercise programs are no more effective than Hip-only exercise programs.

Relationship between kinematic gait parameters during three gait modifications designed to reduce peak knee abduction moment

PurposeGait modifications designed to change a single kinematic parameter have reduced first peak internal knee abduction moment (PKAM). Prior research suggests unintended temporospatial and kinematic changes occur naturally while performing these modifications. We aimed to investigate i) the concomitant kinematic and temporospatial changes and ii) the relationship between gait parameters during three gait modifications (toe-in, medial knee thrust, and trunk lean gait). MethodsUsing visual real-time biofeedback, we collected 10 trials for each modification using individualized target gait parameters based on participants’ baseline mean and standard deviation. Repeated measures ANOVA was performed to determine significant differences between conditions. Mixed effects linear regression models were then used to estimate the linear relationships among variables during each gait modification. All modifications reduced KAM by at least 5%. ResultsModifications resulted in numerous secondary changes between conditions such as increased knee abduction during toe-in gait and increased knee flexion with medial knee thrust. Within gait modifications, relationships between kinematic parameters were similar for toe-in gait and medial knee thrust (i.e. increased toe-in and decreased knee abduction), while increased trunk lean showed no relationship with any other kinematic parameters during trunk lean trials. ConclusionTwo main mechanisms were found as a result of this investigation; the first being a pattern of toeing-in, knee abduction, flexion, and internal hip rotation, while trunk lean modification presented as a separate gait pattern with limited secondary changes. Future studies should consider providing feedback on multiple linked parameters, as it may feel more natural and optimize KAM reductions.

Enzyme replacement therapy in lysosomal acid lipase deficiency (LAL-D): a systematic literature review.

Lysosomal acid lipase deficiency (LAL-D) is a very rare genetic abnormality caused by LIPA gene mutation. The disease has two distinct clinical variants in humans: Wolman disease in infants and cholesteryl ester storage disease in children and adults. Both conditions are characterized by elevated serum transaminases, dyslipidaemia, severe liver steatosis and accelerated fibrosis or cirrhosis, contributing to its high rate of early mortality. Recently sebelipase alfa (recombinant human LAL) was launched to address its underlying pathology. This systematic review evaluates the safety and efficacy of sebelipase alfa for LAL-D. This systematic review was performed following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Clinical trial records were systematically searched in PubMed/Medline, ClinicalTrials.gov., Cochrane Library and Google Scholar up to September 2020. Records that have reported at least one of the included outcomes were included. Baseline and endpoint mean and standard deviation (SD) for all outcomes were recorded. For safety, frequency and overall distribution of different adverse events were included. A total of seven records from five individual studies with 110 LAL-D patients were included into this study. The mean age ranged from 2.57 months in infants to 31.6 years among adults. Serum transaminases (alanine aminotransferase and aspartate aminotransferase), serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol), gamma-glutamyl transferase and liver volume were included as efficacy outcomes. Final pooled results were synthesized as a change from baseline to end of the treatment. A significant effect on both serum transaminases and other serum lipid was achieved (p < 0.01), while non-significant differences were seen for GGT and liver volume as p = 0.35 and p = 0.08 was observed. Mostly the adverse events related to the infusions were infrequent and mild-to-moderate in severity. Sebelipase alfa as an enzyme replacement provides an effective, safe and well tolerated treatment in both variants of LAL-D. A systematic literature review on safety and efficacy of enzyme replacement therapy in lysosomal acid lipase deficiency Lysosomal acid lipase deficiency (LAL-D) is a rare, progressive, genetic disorder caused by functional mutations in the LIPA gene, which encodes LAL enzyme. This enzyme maintains lipid homeostasis by hydrolysing the cholesterol esters and triglycerides. Patients with deficient LAL activity are seen with abnormal liver functions which keep them at a high risk of early mortality. Clinical diagnosis of this disease is very challenging due to both its low prevalence and low awareness among patients/clinicians and additionally due to its overlap with other liver/lipid disorders. Also, owing to lack of safe and effective treatment, dietary modifications and some lipid modifying drugs are usually used to control the LAL-D manifestations. Recently, recombinant human LAL named as sebelipase alfa (Kanuma™, Alexion Pharmaceuticals, Inc., New Haven, Connecticut, USA) was approved in 2015 for the European Union and subsequently in the United States as an enzyme replacement therapy for LAL deficiency. The initial clinical trial data indicate that sebelipase alfa produces a significant improvement in all of the wide range of LAL-D manifestations. However, the cumulative evidence is not reported regarding its safety and effective use. Therefore, a systematic literature review of all the clinical trial records by following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was undertaken. From all of the available clinical trial records, 110 LAL-D patients treated with sebelipase alfa were included. Serum transaminases, serum lipids, gamma-glutamyl transferase (GGT) and liver volume were included as efficacy outcomes. Final pooled results were synthesized as a change from baseline to end of the treatment. A significant effect on both serum transaminases and other serum lipids was achieved (p < 0.01), while non-significant differences were observed for GGT and liver volume, with p = 0.35 and p = 0.08 respectively. Mostly the adverse events related to the infusions were infrequent and mild-to-moderate in severity. The enzyme replacement provides an effective, safe and well tolerated treatment in both variants of LAL-D.