Primary Clinical Outcome Measure Research Articles

PROMPT to improve speech motor abilities in children with cerebral palsy: a wait-list control group trial protocol

BackgroundChildren with cerebral palsy (CP) often have communication impairments, including speech altered intelligibility. Multiple levels of disrupted speech have been reported in CP, which negatively impact on participation and quality of life, with increase of care needs. Augmentative Alternative Communication (AAC) is an option, with debated benefits and limitations, in particular for its functional use. This is supported by a substantial lack of defined evidences in favor of direct speech articulation intervention in CP. Motor learning-based interventions are effective in CP and are the basis of speech motor interventions such as PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets). The PROMPT speech motor treatment provides tactile-kinesthetic inputs to facilitate articulatory movements by dynamic modelling, resulting in more efficient motor patterns that can be integrated into speech and communication. In CP, exploratory evidences support the feasibility and preliminarily advantages on intelligibility of motor speech treatments, such as PROMPT, with increased speech motor control, also documented by kinematic analyses.MethodsA randomized waitlist-control trial will be conducted in children aged between 3- and 10-years having CP and dysarthria (estimated sample size = 60 children). Children will be allocated in the immediate intervention or in the waitlist control group. The intervention consists of an intensive 3 weeks period of twice-a-day administration of PROMPT. Standard care will be administered in the control (waitlist) group. After repeated baseline assessments (T0), the PROMPT treated group will undergo the experimental 3-week intervention period, with T1 assessment at the end. A further T2 assessment will be provided at medium term (3 months after the end of the intervention) for evaluating the stability of intervention. Primary and secondary speech clinical and kinematics outcome measures will be collected at T0, T1 and T2.DiscussionThis paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the or short-term benefits of an intensive speech motor intervention on speech and intelligibility in children with CP and the stability of the intervention at medium term; (2) to describe the kinematic correlates of speech motor control modifications.Trial registrationTrial registration date 06/12/2019; ClinicalTrials.gov Identifier: NCT04189159.

Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.

Evaluation and Outcome of IA Hyaluronic Inj. vs. Corticosteroid Therapy for OA Knee: Tertiary Level Hospital in Bangladesh

Background: There are many types of arthritis, but osteoarthritis (OA) is one of the most frequent. IA injections of corticosteroids into the knee joint may improve pain and impairment by relieving joint inflammation. Purpose: To evaluate the effectiveness and safety of hylastan, a novel viscosupplements, with a single intra-articular corticosteroid injection in the treatment of knee osteoarthritis pain (OA). Because of its large molecular weight, the sodium hyaluronate in Hylastan is more likely to stay in the joint for an extended period of time than other viscosupplements. Methods: Multicentered based randomized quasi-experimental comparative study was performed in Shah Mokhdum Medical College, Rajshahi, Bangladesh, from January 2019 to December 2021. Enrolled patients aged ≥40 years. Patients were randomized 1:1:1 to one of three arms: 2 X 4 mL hylastan (n = 129; arthrocentesis then IA hylastan Day 0, same treatment Week 2); 1 X 4 mL hylastan (n = 130; arthrocentesis then IA hylastan Day 0, arthrocentesis only Week 2); steroid (n = 132; arthrocentesis then IA methylprednisolone acetate 40 mg Day 0, arthrocentesis only Week 2). The primary clinical outcome measure was changed from baseline in WOMAC A pain score overall postbaseline visits to Week 26. Results: Statistically significant pain reduction was observed in all three arms, with similar mean (95 % CI) changes in WOMAC A: 2 X 4 mL hylastan -0.9 (-1.0, -0.7); 1 X 4 mL hylastan -0.8 (-0.9, -0.7); steroid -0.9 (-1.0, -0.8); all p < 0.0001 versus baseline. Changes in secondary outcomes were similar in all three arms. Target knee adverse events were comparable for all treatments. Conclusions: An acceptable safety profile and effective pain relief were found with both IA hylastan injection regimens. The hypothesis of better pain relief with IA hylastan was not met compared to IA corticosteroid. The effectiveness and safety of hylastan compared to other viscosupplements require more investigation. Level of evidence Therapeutic study, Level I.

Dexmedetomidine combined with ropivacaine for erector spinae plane block after posterior lumbar spine surgery: a randomized controlled trial

PurposeDue to lumbar spinal surgery is frequently accompanied with moderate-to-severe postoperative pain, it is necessary to find an effective postoperative analgesia for patients with this surgery. This study aimed to observe the analgesic effect of dexmedetomidine combined with ropivacaine erector spinae plane block (ESPB) used in posterior lumbar spine surgery.MethodsIn this clinical trial, patients undergoing posterior lumbar spine surgery were recruited and randomly divided into two groups: intervention and control. The intervention group (Group E) received 0.375% ropivacaine with 1 µg/kg dexmedetomidine in a total of 20 ml for ESPB; the control group (Group C) received 20 ml ropivacaine 0.375% for ESPB. US-guided ESPB was performed preoperatively in all patients. Demographics, anesthesia time, surgery time, and ASA grade from the participants were recorded at baseline. The primary clinical outcome measures were 2-, 4-, 8-, 12-, 24-and 48-h visual analog scale (VAS) pain scores after surgery at rest and movement state. Other end points included opioid consumption, number of PCIA presses, flurbiprofen-axetil consumption, quality of recovery and pain management after surgery.ResultsOne hundred twenty patients were enrolled in the study (mean [SD] ages: Group E, 54.77 [8.61] years old; Group C,56.40 [7.87] years old; P = 0.280). The mean anesthesia time was 152.55 (15.37) min in Group E and 152.60 (16.47) min in Group C (P = 0.986). Additionally, the surgery time was 141.70 (15.71) min in Group E compared to 141.48 (17.13) min in Group C (P = 0.943). In addition, we found that the VAS pain scores in the resting state during the postoperative period at 8–48 h were lower in Group E than in Group C. However, the VAS pain scores in the active state were lower in Group E at 12–48 h (P < 0.05). More importantly, the consumption of opioids and flurbiprofen-axetil after surgery was also lower in Group E (P < 0.05). Subsequently, we administered questionnaires on the quality of recovery and pain management after surgery that were positively correlated with the postoperative analgesic effect. It was worth affirming that the QoR-15 scores and APS-POQ-R questionnaire results were different between the two groups, further confirming that the combination of drugs not only could obtain an ideal analgesic effect but also had no obvious adverse reactions (P < 0.05).ConclusionsAll the findings suggested that dexmedetomidine could significantly relieve postoperative pain and reduce the consumption of opioids in patients undergoing posterior lumbar spine surgery without obvious adverse reactions as a local anesthetic adjuvant. Further studies with larger sample sizes and different drug dosages may be useful in understanding the potential clinical benefits of dexmedetomidine.

Shockwave lithotripsy compared with ureteroscopic stone treatment for adults with ureteric stones: the TISU non-inferiority RCT.

Urinary stone disease affects 2-3% of the general population. Ureteric stones are associated with severe pain and can have a significant impact on a patient's quality of life. Most ureteric stones are expected to pass spontaneously with supportive care; however, between one-fifth and one-third of patients require an active intervention. The two standard interventions are shockwave lithotripsy and ureteroscopic stone treatment. Both treatments are effective, but they differ in terms of invasiveness, anaesthetic requirement, treatment setting, number of procedures, complications, patient-reported outcomes and cost. There is uncertainty around which is the more clinically effective and cost-effective treatment. To determine if shockwave lithotripsy is clinically effective and cost-effective compared with ureteroscopic stone treatment in adults with ureteric stones who are judged to require active intervention. A pragmatic, multicentre, non-inferiority, randomised controlled trial of shockwave lithotripsy as a first-line treatment option compared with primary ureteroscopic stone treatment for ureteric stones. Urology departments in 25 NHS hospitals in the UK. Adults aged ≥ 16 years presenting with a single ureteric stone in any segment of the ureter, confirmed by computerised tomography, who were able to undergo either shockwave lithotripsy or ureteroscopic stone treatment and to complete trial procedures. Eligible participants were randomised 1 : 1 to shockwave lithotripsy (up to two sessions) or ureteroscopic stone treatment. The primary clinical outcome measure was resolution of the stone episode (stone clearance), which was operationally defined as 'no further intervention required to facilitate stone clearance' up to 6 months from randomisation. This was determined from 8-week and 6-month case report forms and any additional hospital visit case report form that was completed by research staff. The primary economic outcome measure was the incremental cost per quality-adjusted life-year gained at 6 months from randomisation. We estimated costs from NHS resources and calculated quality-adjusted life-years from participant completion of the EuroQol-5 Dimensions, three-level version, at baseline, pre intervention, 1 week post intervention and 8 weeks and 6 months post randomisation. In the shockwave lithotripsy arm, 67 out of 302 (22.2%) participants needed further treatment. In the ureteroscopic stone treatment arm, 31 out of 302 (10.3%) participants needed further treatment. The absolute risk difference was 11.4% (95% confidence interval 5.0% to 17.8%); the upper bound of the 95% confidence interval ruled out the prespecified margin of non-inferiority (which was 20%). The mean quality-adjusted life-year difference (shockwave lithotripsy vs. ureteroscopic stone treatment) was -0.021 (95% confidence interval 0.033 to -0.010) and the mean cost difference was -£809 (95% confidence interval -£1061 to -£551). The probability that shockwave lithotripsy is cost-effective is 79% at a threshold of society's willingness to pay for a quality-adjusted life-year of £30,000. The CEAC is derived from the joint distribution of incremental costs and incremental effects. Most of the results fall in the south-west quadrant of the cost effectiveness plane as SWL always costs less but is less effective. A limitation of the trial was low return and completion rates of patient questionnaires. The study was initially powered for 500 patients in each arm; however, the total number of patients recruited was only 307 and 306 patients in the ureteroscopic stone treatment and shockwave lithotripsy arms, respectively. Patients receiving shockwave lithotripsy needed more further interventions than those receiving primary ureteroscopic retrieval, although the overall costs for those receiving the shockwave treatment were lower. The absolute risk difference between the two clinical pathways (11.4%) was lower than expected and at a level that is acceptable to clinicians and patients. The shockwave lithotripsy pathway is more cost-effective in an NHS setting, but results in lower quality of life. (1) The generic health-related quality-of-life tools used in this study do not fully capture the impact of the various treatment pathways on patients. A condition-specific health-related quality-of-life tool should be developed. (2) Reporting of ureteric stone trials would benefit from agreement on a core outcome set that would ensure that future trials are easier to compare. This trial is registered as ISRCTN92289221. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 19. See the NIHR Journals Library website for further project information.

The effect of combined action observation therapy and eccentric exercises in the treatment of mid-portion Achilles tendinopathy: study protocol for a feasibility pilot randomised controlled trial

BackgroundMid-portion Achilles tendinopathy (AT) is a common overuse injury which can be difficult to successfully rehabilitate. Whilst peripherally directed treatment approaches that strengthen the Achilles tendon complex can be efficacious for some individuals, others will continue to experience long-standing pain and functional deficits. Expanding our rehabilitation approach beyond the tendon mechanical properties to include techniques which target the central neurophysiological changes which can occur in chronic injuries, including mid-portion AT, may improve our rehabilitation outcomes. Action observation therapy (AOT) is one such technique which targets central changes and can enhance motor learning. To our knowledge, there is currently no available information on the combined effect of AOT and eccentric exercises in the rehabilitation of mid-portion AT, nor understanding of the feasibility of conducting randomised controlled trials that investigate this combined centrally and peripherally directed treatment approach. This protocol outlines the design of a remotely conducted parallel-group randomised controlled trial comparing the efficacy of combined AOT and eccentric loading exercises versus eccentric loading exercises alone for mid-portion AT.MethodsParticipants recruited throughout Ireland with mid-portion AT will be randomly assigned to one of the following groups: (i) The AOT group will observe videos of the eccentric exercises prior to the physical performance of the eccentric exercises. (ii) The control group will observe videos of landscapes prior to the performance of the eccentric exercises. This is a 12-week daily intervention as per the Alfredson loading protocol and outcome measures will be assessed at baseline, week 6 and week 12. Primary feasibility outcomes will include data on numbers of eligible participants, recruitment and retention rates, along with exercise compliance and acceptability of treatment. The primary clinical outcome measure will be the Victorian Institution Symptom Assessment-Achilles Questionnaire (VISA-A) assessing disability. Secondary clinical outcomes will address the remaining core domains as outlined by the International Scientific Tendinopathy Symposium consensus (ICON group) including pain, participation, functional, physical function capacity, quality of life and psychological factors. Widespread bodily pain and centralised pain features and patient satisfaction levels will also be evaluated.DiscussionThis study will provide scientific direction for future randomised controlled trials exploring the effect of AOT and eccentric exercises in the treatment of mid-portion AT on pain, centralised pain features, motor and non-motor functions, quality of life and patient satisfaction levels. The feasibility of the conducting a study remotely from participant screening to final follow-up assessment will also be provided.Trial registrationISRCTN58161116

Effect of different durations of using a standing frame on the rate of hip migration in children with moderate to severe cerebral palsy: a feasibility study for a randomised controlled trial

AimTo assess the feasibility of a randomised controlled trial (RCT) to evaluate the effect of different doses of standing time on hip migration rate in children with cerebral palsy (CP). MethodChildren aged 1–12 years with CP GMFCS levels III–V were recruited and randomised to either doubling or continuing with their usual time in their standing frame. Caregivers kept a standing time diary. The primary outcome measure was Reimers hip migration percentage, measured at baseline, 12 and 24 months. A blinded assessor measured secondary clinical outcomes at baseline, 6 and 12 months. Feasibility results are reported following CONSORT guidelines. ResultsTwenty-five children were recruited. Nineteen were randomised and 10 completed the 12-month intervention. The mean daily standing time in the intervention group was 49minutes (SD 39.1) (Monday–Sunday) and 58.1 (SD 44.1) minutes during weekdays. In children remaining in the trial, primary and secondary clinical outcome measures were available in 54% and 90% of children respectively. There were three serious adverse events, unrelated to standing. ConclusionsIt may be feasible to conduct an RCT to assess the effect of duration of standing on hip migration in children with CP with an altered protocol. The suggested target dose is 60minutes five times per week compared to a control group standing for 30minutes three times per week, over twelve months. Use of botulinum toxin need not be a criterion for exclusion and radiography should be included as a research cost.NHS Health Research Committee, South West ethics approval (ref 13/SW/0228).

Neurofeedback-guided kinesthetic motor imagery training in Parkinson’s disease: Randomized trial

BackgroundParkinson’s disease (PD) causes difficulty with maintaining the speed, size, and vigor of movements, especially when they are internally generated. We previously proposed that the insula is important in motivating intentional movement via its connections with the dorsomedial frontal cortex (dmFC). We demonstrated that subjects with PD can increase the right insula-dmFC functional connectivity using fMRI-based neurofeedback (NF) combined with kinesthetic motor imagery (MI). The current study is a randomized clinical trial testing whether NF-guided kinesthetic MI training can improve motor performance and increase task-based and resting-state right insula-dmFC functional connectivity in subjects with PD. MethodsWe assigned nondemented subjects with mild PD (Hoehn & Yahr stage ≤ 3) to the experimental kinesthetic MI with NF (MI-NF, n = 22) and active control visual imagery (VI, n = 22) groups. Only the MI-NF group received NF-guided MI training (10–12 runs). The NF signal was based on the right insula-dmFC functional connectivity strength. All subjects also practiced their respective imagery tasks at home daily for 4 weeks. Post-training changes in 1) task-based and resting-state right insula-dmFC functional connectivity were the primary imaging outcomes, and 2) MDS-UPDRS motor exam and motor function scores were the primary and secondary clinical outcomes, respectively. ResultsThe MI-NF group was not significantly different from the VI group in any of the primary imaging or clinical outcome measures. The MI-NF group reported subjective improvement in kinesthetic body awareness. There was significant and comparable improvement only in motor function scores in both groups (secondary clinical outcome). This improvement correlated with NF regulation of the right insula-dmFC functional connectivity only in the MI-NF group. Both groups showed specific training effects in whole-brain functional connectivity with distinct neural circuits supporting kinesthetic motor and visual imagery (exploratory imaging outcome). ConclusionsThe functional connectivity-based NF regulation was unsuccessful, however, both kinesthetic MI and VI practice improved motor function in our cohort with mild PD.

Two Year Patient Reported Outcomes of 334 Minimally Invasive Chevron Akin Osteotomies (MICA) in Hallux Valgus Surgery

Category:Bunion; Midfoot/ForefootIntroduction/Purpose:There are many different procedures described for the correction of hallux valgus deformity. Minimally invasive surgery has become increasingly popular, with clinical and radiological outcomes comparable to traditional open osteotomy approaches. There is increasing interest in hallux valgus deformity correction using third-generation minimally invasive chevron akin osteotomy (MICA) technique. Objective: To assess the radiographic correction and 2-year clinical outcomes of third-generation MICA using validated outcome measures.Methods:This is a prospective single-surgeon case series of 420 consecutive feet undergoing MICA surgery between July 2014 and Jan 2019. Primary clinical outcome measures included the Manchester-Oxford Foot Questionnaire (MOXFQ), EQ-5D, and the Visual Analogue Pain Scale. Secondary outcome measures included radiographic parameters, and complication rates.Results:Pre-operative and 2 year post-operative patient reported outcomes were collected for 334 feet (79.5%). At minimum 2 year follow-up, the MOXFQ scores (mean +- standard deviation (SD)) had improved for each domain: pain; pre-operative 43.9+- 21.0 reduced to 9.1+-15.6 post-operatively (p<0.001), walking and standing; pre-operative 38.2+-23.6 reduced to 6.5+-14.5 post- operatively (p<0.001) and social interaction; pre-operative 47.6+-22.1, reduced to 6.5+-13.5 post-operatively (p<0.001). At 2 year follow-up, the VAS Pain score (mean +- SD) improved from a pre-operative of 31.3+-22.4 to 8.3+-16.2 post-operatively (p<0.001). 1-2 intermetatarsal angle (mean +- SD) reduced from 15.4°+-3.5° to 5.8°+-3.1° (p<0.001) and hallux valgus angle reduced from 33.1°+-10.2° to 9.0°+-5.0° post-operatively (p<0.001).Conclusion:Third-generation MICA showed significant improvement in clinical outcomes at 2 year follow-up and can be successfully used for correction of a wide range of hallux valgus deformities.

Effectiveness of Radial Extracorporeal Shock Wave Therapy and Visual Feedback Balance Training on Lower Limb Post-Stroke Spasticity, Trunk Performance, and Balance: A Randomized Controlled Trial.

Stroke remains one of the leading causes of disability in adults, and lower limb spasticity, affected stance, and balance impact everyday life and activities of such patients. Robotic therapy and assessment are becoming important tools to clinical evaluation for post-stroke rehabilitation. The aim of this study was to determine in a more objective manner the effects of visual feedback balance training through a balance trainer system and radial extracorporeal shock wave therapy (rESWT), along with conventional physiotherapy, on lower limb post-stroke spasticity, trunk control, and static and dynamic balance through clinical and stabilometric assessment. The study was designed as a randomized controlled trial. The experimental group underwent conventional physiotherapy, visual feedback balance training, and rESWT. The control group underwent conventional physiotherapy, visual feedback training and sham rESWT. The statistical analysis was performed using GraphPad Software and MATLAB. Primary clinical outcome measures were The Modified Ashworth Scale (MAS), passive range of motion (PROM), Visual Analogue Scale (VAS), and Clonus score. Secondary outcome measures were trunk performance, sensorimotor, and lower limb function. Stabilometric outcome measures were trunk control, static balance, and dynamic balance. Visual feedback training using the Prokin system and rESWT intervention, along with conventional physiotherapy, yielded statistically significant improvement both on clinical and stabilometric outcome measures, enhancing static and dynamic balance, trunk performance, sensorimotor outcome, and limb function and considerably diminishing lower limb spasticity, pain intensity, and clonus score in the experimental group.

Investigating EEG biomarkers of clinical response to low frequency rTMS in depression

Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention for major depressive disorder (MDD). Completing a full treatment course, however, is costly and time-consuming. Biomarkers of clinical outcome such as baseline resting-state brain activity measured with electroencephalography (EEG) may spare people futile treatment and conserve limited clinical resources. Additionally, investigating changes in EEG power post-treatment could provide insights into the working mechanism of rTMS. 39 MDD patients received 6 daily sessions of accelerated low-frequency (LF) rTMS over the right dorsolateral prefrontal cortex (DLPFC) for 5 days followed by a tapering course of 25 once-daily sessions. Resting-state EEG and heart rate (HR) measures were acquired immediately before and after a single rTMS session at 3 different timepoints: baseline, one week after the final accelerated session, and upon completion of the tapering course. The primary clinical outcome measure was the Beck Depression Inventory II (BDI-II). High relative baseline theta power in prefrontal areas and high baseline HR were associated with poorer clinical outcome. HR decreased acutely at the beginning of the patients’ first rTMS session but this effect was not associated with treatment outcome. The main limitations were small sample size and a lack of sham and healthy control group. Our results suggest that high relative theta power at baseline may be a marker of poorer response to right-sided LF rTMS. If validated, this easily applicable measure could inform rTMS protocol choice for the individual, thereby potentially speeding up patient recovery and saving clinical resources.

Abstract 10191: Dapagliflozin versus Empagliflozin for Improving Outcomes of Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction

Introduction: Patients with HF and reduced ejection fraction (HFrEF) are at high risk for CV mortality and HF-related hospitalizations (HHF). The Sodium-Glucose Transport protein 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin improve the outcomes of non-diabetic patients with HFrEF. We aimed to compare their value for money for this indication. Hypothesis: Empagliflozin and dapagliflozin have comparable value for money for improving the HF outcomes of non-diabetic patients with HFrEF. Methods: SGLT2i data was extracted from published results of empagliflozin and dapagliflozin in the subgroups of patients without diabetes. The primary clinical outcome measure was a composite of HHF or CV mortality events. The economic measure was the cost needed to treat (CNT) to prevent one event, calculated by multiplying the one-year number needed to treat (NNT) to prevent one event by the annual cost of each therapy. Drug costs were based on the 2021 US National Average Drug Acquisition Cost prices. Secondary outcomes were the CNT to prevent one event of HHF and CV mortality as separate clinical outcomes. Sensitivity analysis was performed to mitigate differences between the trial’s populations Results: Treatment with empagliflozin in EMPEROR-REDUCED has resulted in an NNT of 29 (95% CI: 18-212) compared to 32 (95% CI: 21-72) with dapagliflozin in DAPA-HF. Accordingly the CNT to prevent one event of CVM or HHF was $139,115 (95% CI: $86,347-$1,016,976) and $144,751 (95% CI: $94,993-$325,690), respectively. The sensitivity analysis confirmed the primary results, but the CNT to prevent CV mortality is significantly lower with dapagliflozin (Fig. 1) Conclusions: Empagliflozin and dapagliflozin have comparable value for money for improving HF outcomes of non-diabetic patients with HFrEF, with an advantage for dapagliflozin in CV mortality.

Does adding hip strengthening exercises to manual therapy and segmental stabilization improve outcomes in patients with nonspecific low back pain? A randomized controlled trial

BackgroundThe literature is unclear on the need for hip strengthening in persons with low back pain (LBP). ObjectivesTo investigate the effectiveness of hip strengthening exercises when added to manual therapy and lumbar segmental stabilization in patients with chronic nonspecific LBP. MethodsSeventy patients with chronic nonspecific LBP were randomly assigned to either the manual therapy and lumbar segmental stabilization group or the manual therapy and lumbar segmental stabilization plus specific hip strengthening group. A 10 cm visual analogue scale and the Rolland-Morris Questionnaire were the primary clinical outcome measures at baseline, at the end of treatment (posttreatment), and 6- and 12-months posttreatment. Hip strength and kinematics were measured as secondary outcomes . ResultsWhile within-group improvements in pain, disability, and hip extensors strength occurred in both groups, there were no significant between-group differences at posttreatment or follow-ups. Mean difference in changes in pain level between groups at posttreatment and at 6- and 12-month follow-up were 0.5 points (95% confidence interval [CI]: -0.5, 1.5), 0.3 points (95% CI: -0.9, 1.5), and 0.0 points (95% CI: -1.1, 1.1), respectively. The mean differences in changes in disability were 0.8 points (95% CI: -1.3, 2.7), 0.0 points (95% CI: -2.4, 2.4), and 0.4 points (95% CI: -2.0, 2.8), respectively. Finally, we did not observe any between-group differences for any of the other outcomes at any timepoint. ConclusionThe addition of specific hip strengthening does not appear to result in improved clinical outcomes for patients with nonspecific LBP.

18.4 IMAGING THE TREATMENT OF ADHD

ADHD is one of the most common mental health disorders affecting children. Psychostimulants are a first-line treatment for ADHD, but common side effects often result in discontinuation. Moreover, the long-term efficacy of psychostimulants remains unclear. Identifying the neural mechanisms by which psychostimulants attenuate ADHD symptoms may guide the development of more refined and tolerable therapeutics. In this work, we aim to identify causal effects of psychostimulants on brain connectivity in individuals with ADHD and their relationship with symptom improvement. In a 12-week, randomized, placebo-controlled trial of lisdexamfetamine (LDEX), 49 out of 58 eligible participants (12.6 [5.7] years; 33 [67%] males; 25 LDEX and 24 placebo) completed both pre– and post–randomized controlled trial MRI scanning with adequate data quality. The primary clinical outcome measures are T scores on ADHD symptom scales assessed with the Conners’ Parent Rating Scale and the Conners’ Adult ADHD Rating Scale. Treatment effects on striatal and thalamic functional connectivity (FC) are identified using both static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. We also examined whether treatment-induced connectivity changes acted on connections that differed between those with ADHD and healthy controls (HCs). An HC group (n = 46) matched on age and sex was included for comparison. Analyses were then repeated in independent samples from the ABCD study (n = 103) and the New York University ADHD-200 Consortium cohort (n = 213). We found that LDEX resulted in increasing static and decreasing dynamic FC. However, there were only dynamic mediated therapeutic effects of LDEX. Additionally, at baseline, dynamic FC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings: ADHD was associated with increased dynamic FC, and psychostimulants with reduced dynamic FC. We found that changes in dynamic, not static, FC accounted for therapeutic effects of psychostimulants. Altered dynamic FC may represent a reliable target for new ADHD interventions aimed at stabilizing network dynamics.

Polymicrobial and monomicrobial necrotizing soft tissue infections: comparison of clinical, laboratory, radiological, and pathological hallmarks and prognosis. A retrospective analysis

BackgroundNecrotizing soft tissue infection (NSTI) is a life-threatening infection associated with high morbidity and mortality. Treatment consists of surgery and antibiotics. Many studies have addressed NSTI and its subtypes, but...

Long-Term Follow-Up Results of Mechanical Wrist Traction as Non-Invasive Treatment for Carpal Tunnel Syndrome.

Background: For patients with carpal tunnel syndrome (CTS), the only long-term effective treatment option is carpal tunnel release surgery. Up to one-third report recurrent symptoms, and 12% needs repeated surgery. This study aimed to evaluate the long-term effects of mechanical traction as a non-invasive treatment option for CTS compared to care as usual.Methods: Patients with electrodiagnostically confirmed CTS [N = 181; mean age, 58.1 (13.0) years; 67% women] were recruited from an outpatient neurology clinic in the Netherlands. Patients completed baseline questionnaires and randomized to the intervention group (12 treatments with mechanical traction, twice a week for 6 weeks) or care as usual. The primary clinical outcome measure was surgery during the 12-month follow-up. Secondly, we assessed symptom severity with the Boston Carpal Tunnel Questionnaire (BCTQ) at baseline and at the 12-month follow-up. Changes in CTS symptom severity between baseline and the 12-month follow-up were analyzed between groups using t-tests and a multiple linear regression analyses, adjusting for duration of complaints, age, gender, and symptom severity at baseline.Results: At the 12-month follow-up, 35 of 94 (37%) patients in the intervention group had surgery, compared to 38 of 87 (44%) in the care-as-usual group ( = 0.78, p = 0.377). Symptom severity and functional status scores did not significantly differ between the intervention (n = 81) and care-as-usual group (n = 55) at follow-up. For patients who did not have surgery, BCTQ scores decreased significantly more from baseline to the 12-month follow-up in the intervention group (n = 53) compared to patients in the care-as-usual group (n = 25). For patients who did not have surgery, belonging to the intervention group and a higher BCTQ score at baseline were related to a greater decrease in BCTQ scores from baseline to the 12-month follow-up, as well as symptom severity and functional status.Conclusions: Mechanical traction is effective in reducing symptom severity compared to current conservative treatment options in standard care and can therefore benefit the large number of patients that prefer conservative treatment for CTS.Clinical Trial Registration: Clinical Trials NL44692.008.13. Registered 19 September 2013, https://clinicaltrials.gov/ct2/show/NCT01949493

Clinical Outcomes Following Acute Residential Psychiatric Treatment in Transgender and Gender Diverse Adolescents

Transgender and gender diverse (TGD) individuals, who have a gender identity that differs from their sex assigned at birth, are at increased risk of mental health problems, including depression, anxiety, self-injurious behavior, and suicidality, relative to cisgender peers. To examine mental health outcomes among TGD vs cisgender adolescents in residential treatment. This cohort study's longitudinal design was used to compare groups at treatment entry and discharge, and 1-month postdischarge follow-up. The setting was an adolescent acute residential treatment program for psychiatric disorders. Participants were TGD or cisgender adolescents enrolled in the treatment program. Statistical analysis was performed October 2019 to March 2021. Adolescents participated in a 2-week acute residential treatment program for psychiatric disorders. Primary outcomes were depressive (the Center for Epidemiologic Studies Depression Scale [CES-D]) and anxiety (the Multidimensional Anxiety Scale for Children [MASC]) symptoms, and emotional dysregulation (the Difficulties in Emotion Regulation Scale [DERS]), measured at treatment entry and discharge, and postdischarge follow-up. Age of depression onset, suicidality, self-injury, and childhood trauma also were assessed at treatment entry. Of 200 adolescent participants who completed treatment entry and discharge assessments, the mean (SD) age was 16.2 (1.5) years; 109 reported being assigned female at birth (54.5%), 35 were TGD (17.5%), and 66 (49.3%) completed 1-month follow-up. TGD participants had an earlier mean (SD) age of depression onset (TGD: 10.8 [2.4] years vs cisgender: 11.9 [2.3] years; difference: 1.07 years; 95% CI, 0.14-2.01 years; P = .02), higher mean (SD) suicidality scores (TGD: 44.4 [23.1] vs cisgender: 28.5 [25.4]; difference: 16.0; 95% CI, 6.4-25.5; P = .001), more self-injurious behavior (mean [SD] RBQ-A score for TGD: 3.1 [2.5] vs cisgender: 1.7 [1.9]; difference: 1.42; 95% CI, 0.69-2.21; P = .001) and more childhood trauma (eg, mean [SD] CTQ-SF score for emotional abuse in TGD: 12.7 [5.4] vs cisgender: 9.8 [4.7]; difference: 2.85; 95% CI, 1.06-4.64; P = .002). The TGD group also had higher symptom scores (CES-D mean difference: 7.69; 95% CI, 3.30 to 12.08; P < .001; MASC mean difference: 7.56; 95% CI, 0.46 to 14.66; P = .04; and DERS mean difference: 18.43; 95% CI, 8.39 to 28.47; P < .001). Symptom scores were significantly higher at entry vs discharge (CES-D mean difference, -12.16; 95% CI, -14.50 to -9.80; P < .001; MASC mean difference: -3.79; 95% CI, -6.16 to -1.42; P = .02; and DERS mean difference: -6.37; 95% CI, -10.80 to -1.94; P = .05) and follow-up (CES-D mean difference: -9.69; 95% CI, -13.0 to -6.42; P < .001; MASC mean difference: -6.92; 95% CI, -10.25 to -3.59; P < .001; and DERS mean difference: -12.47; 95% CI, -18.68 to -6.26; P < .001). This cohort study found mental health disparities in TGD youth relative to cisgender youth, with worse scores observed across assessment time points. For all participants, primary clinical outcome measures were significantly lower at treatment discharge than at entry, with no significant differences between discharge and 1-month follow-up. Given the substantial degree of mental health disparities reported in TGD individuals, these findings warrant focused clinical attention to optimize treatment outcomes in gender minority populations.

Full-Endoscopic Oblique Lateral Lumbar Interbody Fusion: A Technical Note With 1-Year Follow-Up.

Oblique lateral lumbar interbody fusion (OLLIF) is a minimally invasive lumbar interbody fusion procedure using a bullet-shaped polyetheretherketone (PEEK) nonexpandable fusion cage modified to diminish risk to the exiting nerve root during posterolateral implantation through the Kambin safe zone under fluoroscopic guidance. The objective of this study was to present feasibility of this procedure and 1-year clinical outcome data. The authors present a prospective cohort study of 20 patients who underwent fluoroscopy-guided and full-endoscopic OLLIF in 22 segments allowing protection of the exiting nerve root from January 2018 to March 2019. The foraminoplasty, discectomy, endplate preparation, placement of bone graft and insertion of the fusion cage was done under continuous full-endoscopic visualization. The OLLIF fusion was backed up with bilateral percutaneous posterior supplemental pedicle screw fixation. Primary clinical outcome measures were the visual analog scale (VAS) of low back and leg pain, and Oswestry disability index (ODI) at 1 week, 3 months, 6 months, and 1 year after the operation. At final follow-up, the Macnab score was also evaluated. Secondary outcome measures were computed tomography (CT) assessment fusion using the Mannion classification of spinal fusion and adverse events related to the device as well as magnetic resonance imaging (MRI) assessment of nerve root decompression. All patients had significant relief of low back pain and leg pain, by VAS and ODI scores that improved significantly (P < .01). There were no complications. Postoperative lumbar MRI of all patients showed sufficient direct nerve decompression. At 1-year follow-up, excellent Macnab outcomes were obtained 13 patients, good in six, and fair in one. Impaired sensation and muscle strength of the involved nerve root significantly recovered in all but 2 patients (P < .05). According to the Mannion CT-based classification of spinal fusion, CT showed complete interbody fusion achieved in all 22 segments. Full-endoscopic OLLIF is a safe, effective, minimally invasive, economical, practical, and widely applicable minimally invasive interbody fusion technique in the lumbar spine. 3.

Effects of Ivermectin in Patients With COVID-19: A Multicenter, Double-blind, Randomized, Controlled Clinical Trial

PurposeGiven the coronavirus disease 2019 (COVID-19) pandemic, there is a global urgency to discover an effective treatment for patients withthis disease. This study aimed to evaluate the effects of the widely used antiparasitic drug ivermectin on outcomes in patients with COVID-19. MethodsIn this randomized, double-blind clinical trial, patients with COVID-19 admitted to 2 referral tertiary hospitals in Mazandaran, Iran, were randomly divided into 2 groups: intervention and control. In addition to standard treatment for COVID-19, the intervention group received a single weight-based dose (0.2 mg/kg) of ivermectin; the control group received the standard of care. Demographic, clinical, laboratory, and imaging data from participants were recorded at baseline. Patients were assessed daily for symptoms and disease progression. The primary clinical outcome measures were the durations of hospital stay, fever, dyspnea, and cough; and overall clinical improvement. FindingsSixty-nine patients were enrolled (mean [SD] ages: ivermectin, 47.63 [22.20] years; control, 45.18 [23.11] years; P = 0.65). Eighteen patients (51.4%) in the ivermectin group and 18 (52.9%) in control group were male (P = 0.90). The mean durations of dyspnea were 2.6 (0.4) days in the ivermectin group and 3.8 (0.4) days in the control group (P = 0.048). Also, persistent cough lasted for 3.1 (0.4) days in the ivermectin group compared to 4.8 (0.4) days in control group (PP = 0.019). The mean durations of hospital stay were 7.1 (0.5) days versus 8.4 (0.6) days in the ivermectin and control groups, respectively (P = 0.016). Also, the frequency of lymphopenia decreased to 14.3% in the ivermectin group and did not change in the control group (P = 0.007). ImplicationsA single dose of ivermectin was well-tolerated in symptomatic patients with COVID-19, and important clinical features of COVID-19 were improved with ivermectin use, including dyspnea, cough, and lymphopenia. Further studies with larger sample sizes, different drug dosages, dosing intervals and durations, especially in different stages of the disease, may be useful in understanding the potential clinical benefits ivermectin. Iranian Registry of Clinical Trials identifier: IRCT20111224008507N3.

Third-Generation Minimally Invasive Chevron and Akin Osteotomies (MICA) in Hallux Valgus Surgery: Two-Year Follow-up of 292 Cases.

Background:There is interest in hallux valgus deformity correction using internal fixation with the minimally invasive chevron and Akin osteotomies (MICA) technique. The objective of this study was to assess the correction measured on postoperative radiographs and clinical outcomes, using validated outcome measures, at 2 years following third-generation MICA.Methods:This is a prospective single-surgeon case series of 333 consecutive feet that underwent MICA surgery between July 2014 and April 2018. The primary clinical outcome measures included the Manchester-Oxford Foot Questionnaire (MOXFQ), EuroQol-5 Dimensions-5 Level (EQ-5D-5L) Index, EuroQol-visual analogue scale (EQ-VAS), and a VAS for pain (VAS-pain). Secondary outcome measures included radiographic parameters and complication rates.Results:Preoperative and 2-year postoperative patient-reported outcome measures (PROMs) were collected for 292 feet (87.7%). At a minimum 2-year follow-up, the MOXFQ scores (mean ± standard deviation [SD]) had improved in each domain—i.e., reduced from 44.5 ± 21.0 preoperatively to 9.4 ± 15.8 postoperatively for pain (p < 0.001), from 38.7 ± 23.4 to 6.5 ± 14.6 for walking and standing (p < 0.001), and from 48.0 ± 22.3 to 6.6 ± 13.5 for social interaction (p < 0.001). The VAS-pain score improved from 31.4 ± 22.7 preoperatively to 8.4 ± 16.4 at the 2-year follow-up (p < 0.001), the 1-2 intermetatarsal angle was reduced from 15.3° ± 3.6° preoperatively to 5.7° ± 3.2° at the 2-year follow-up (p < 0.001), and the hallux valgus angle was reduced from 32.9° ± 10.2° to 8.7° ± 5.2° (p < 0.001).Conclusions:The third-generation MICA provided significant improvement in clinical outcome measures at the 2-year follow-up and can be successfully used for correction of a range of hallux valgus deformities with a low rate of symptomatic recurrence.Level of Evidence:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.