Scale Score Research Articles

Association of Conscious Sedation With Dexmedetomidine and Outcome in Stroke Patients Undergoing Thrombectomy in the DEVT and RESCUE-BT Trials.

Although dexmedetomidine (DEX) is widely administered during endovascular treatment (EVT) to enhance procedural adherence of patients with acute ischemic stroke (AIS) with large vessel occlusion, there is limited research on the association of DEX and outcomes among these patients. Hence, this study aimed to explore the safety and outcomes of DEX during conscious sedation (CS) in a real-world setting among patients undergoing EVT. This study was an individual patient-level pooled analysis of 2 multicenter randomized clinical trials RESCUE-BT and DEVT. This study included patients who underwent EVT because of occlusion of the internal carotid artery or middle cerebral artery. The DEX group included those receiving intraprocedural DEX for CS, whereas the patients without intraprocedural DEX sedation were categorized into the non-DEX group. The primary outcome was functional independence (modified Rankin Scale score of 0-2 at 90 days). Adjusted odds ratio (aOR) and 95% CI were obtained by logistic regression models. A total of 728 patients were included in this study, of whom 308 (42.3%) were female. The median (interquartile range) age was 69 (59-76) years; the median baseline NIH Stroke Scale score was 16 (12-19). Compared with the non-DEX group, the DEX group had a significantly lower rate of functional independence (40.3% vs 51.3%; aOR 0.66; 95% CI 0.46-0.93; p = 0.019). There was a significantly higher rate of unstable procedural hemodynamics in the DEX group (9.7% vs 2.3%; aOR 4.60, 95% CI 2.12-9.99, p < 0.001). In subgroup analysis, similar results were found in intraprocedural DEX-treated patients when compared with local anesthesia or intraprocedural midazolam-treated patients, respectively. There was a negative association between procedural DEX administration during CS and functional outcomes in patients with AIS receiving EVT in a real-world setting. A larger cohort is warranted to validate our findings. This study provides Class II evidence that the use of DEX during EVT of AIS is associated with a worse outcome compared with other agents.

Epidemiology and Impact of Social Hardships in Children With Multiple Sclerosis in the United States.

Social determinants of health (SDOH) affect patient health outcomes, but the impact on patients with pediatric-onset multiple sclerosis (POMS) has not been well studied. Study objectives were to (1) describe the frequency of adverse SDOH, (2) evaluate social hardships as a potential barrier to the initiation of disease-modifying therapy (DMT), and (3) explore the association between adverse SDOH and disease outcomes in POMS, as well as study attrition. This was a retrospective multicenter observational study conducted through the United States Network of Pediatric MS Centers database. Participants were patients diagnosed with POMS (excluding primary progressive MS). The primary outcome was time to initiation of DMT. Secondary outcomes included most recent Expanded Disability Status Scale (EDSS) score, steroid treatment for the first event, time to second event, and study attrition. Demographic variables and clinical outcomes were compared between patients with and without hardships (maternal education of high school or less, public insurance/no insurance, or single/no-income household). Multivariable regression models were used to assess the impact of social hardship on study outcomes. There were 996 total participants (69% female, mean age at symptom onset and EDSS score [±SD] were 14.2 ± 3 and 1.2 ± 1.1, respectively). Of 768 patients with complete demographic information, 66% reported a hardship. Hardship was associated with younger age at symptom onset and diagnosis. While there was no difference in time to DMT initiation, patients with hardship were more likely to receive steroids for the first event (odds ratio [OR] 1.66, 95% CI 1.21-2.26, p = 0.002). Lack of private insurance was associated with increased risk of study attrition (OR 1.85, 95% CI 1.14-3.00, p = 0.012) and higher EDSS score (β = 0.15, 95% CI 0.01, 0.28). Living in a no-income household (vs dual-income) was associated with a shorter time to second event (hazard ratio 1.33, 95% CI 1.02-1.74, p = 0.034). The experience of hardships is common and associated with younger age at symptom onset and diagnosis, as well as shorter time to second event. Lack of private insurance is associated with study attrition and a higher EDSS score despite no difference in time to initiating DMT. There may be differences in early disease pathophysiology related to social hardship, and future studies are needed to better understand this complex relationship.

Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results From the ENCHANTED Study.

Hemorrhagic transformation may be a potentially devastating complication of IV thrombolysis (IVT) in acute ischemic stroke, but what degree of hemorrhage indicates the greatest negative effect is not known. We aimed to define the associations between hemorrhagic transformation patterns, classified according to clinical and imaging categories, and clinical outcomes after IVT. We conducted a post hoc analysis from the international Enhanced Control of Hypertension and Thrombolysis Stroke Study. Symptomatic intracerebral hemorrhage (sICH) was defined based on established criteria, such as the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. Asymptomatic intracerebral hemorrhage (aICH) was defined as any intracerebral hemorrhage that did not meet the criteria for sICH. Imaging subtypes of hemorrhagic transformation were assessed using the Heidelberg Bleeding Classification system. The primary outcome was death or major disability, defined by modified Rankin scale (mRS) scores 3-6 at 90 days. Secondary outcomes included death, death or disability (mRS 2-6), and poor health-related quality of life (HRQoL), defined as an overall heath utility score ≤0.7 (mean). Of the 4,370 participants, 779 (17.8%) developed any intracranial hemorrhage (ICH), with a median time from randomization to hemorrhage of 23.5 hours (interquartile range 18.92-26.07). According to the SITS-MOST criteria, 62 patients (1.4% of 4,370) were classified as sICH, and 717 patients (16.4% of 4,370) were classified as aICH. sICH per SITS-MOST criteria was associated with death or major disability (odds ratio [OR] 23.05, 95% CI 8.97-59.23), death (OR 20.14, 95% CI 11.32-35.84), death or disability (OR 61.36, 95% CI 8.40-448.01), and poor HRQoL (OR 17.87, 95% CI 7.47-42.71). Similarly, aICH per SITS-MOST criteria was also associated with death or major disability (OR 2.23, 95% CI 1.84-2.70), death (OR 1.82, 95% CI 1.39-2.38), death or disability (OR 2.29, 95% CI 1.87-2.80), and poor HRQoL (OR 1.81, 95% CI 1.50-2.18). Comparable associations were observed for sICH and aICH defined by other criteria, as well as for imaging subtypes based on Heidelberg Bleeding Classification system. All forms of post-IVT hemorrhagic transformation in acute ischemic stroke are associated with increased odds of poor clinical outcomes. Of note, aICH after IVT should not be considered clinically innocuous. ClinicalTrials.gov (NCT01422616).

Association of Vascular Risk With Severe vs Non-Severe Stroke: An Analysis of the INTERSTROKE Study.

Acute stroke is associated with a spectrum of functional deficits. The objective of this analysis was to explore whether the importance of individual risk factors differ by stroke severity, which may be of relevance to public health strategies to reduce disability. INTERSTROKE is an international case-control study of risk factors of first acute stroke (recruitment 2007-August 2015) in 32 countries. Stroke severity was measured using the modified Rankin Scale (mRS) score within 72 hours of admission to hospital. Severe stroke is defined as mRS scores of 4-6 (and non-severe stroke, score of 0-3). We used multinomial logistic regression to estimate comparative odds ratios (ORs; 95% CIs) for severe and non-severe stroke and tested for heterogeneity (pheterogeneity). We also conducted a matched case-case analysis (matched for age, sex, country, and primary stroke subtype) to determine whether the prevalence of risk factors differed significantly between severe and non-severe stroke. A significant difference in the association of a risk factor of severe stroke compared with non-severe stroke was defined as p < 0.05 for both pheterogeneity and pcase-case. Of patients with acute stroke (n = 13,460), 64.0% (n = 8,612) were reported to have mRS scores of 0-3 and 36.0% (n = 4,848) scores of 4-6. The mean age was 61.7 years for patients with non-severe stroke and 62.9 years for patients with severe stroke (p = 0.72). 38.1% (n = 3,278) of patients with non-severe stroke and 44.6% (n = 2,162) of patients with severe stroke were female. Hypertension (OR 3.21; 95% CI 2.97-3.47 for severe stroke, OR 2.87; 95% CI 2.69-3.05 for non-severe stroke; pheterogeneity = 0.03; pcase-case < 0.001), atrial fibrillation (OR 4.70; 95% CI 4.05-5.45 for severe stroke, OR 3.61; 95% CI 3.16-4.13 for non-severe stroke; pheterogeneity = 0.009; pcase-case < 0.001), and smoking (OR 1.87; 95% CI 1.72-2.03 for severe stroke, OR 1.65; 95% CI 1.54-1.77 for non-severe stroke; pheterogeneity = 0.02; pcase-case < 0.001) had a stronger association with severe stroke, compared with non-severe stroke. The waist-to-hip ratio had a stronger association with non-severe stroke compared with severe stroke (pheterogeneity < 0.001; pcase-case < 0.001). Hypertension, atrial fibrillation, and smoking had a stronger magnitude of association with severe stroke (compared with non-severe stroke) while the increased waist-to-hip ratio had a stronger magnitude of association with non-severe stroke.

Association of Sleep Disturbances With Prevalent and Incident Motoric Cognitive Risk Syndrome in Community-Residing Older Adults.

There is growing evidence that sleep disturbances are associated with cognitive impairment risk, but their association with the incidence of motoric cognitive risk syndrome (MCR)-a predementia syndrome characterized by slow gait speed and cognitive complaints-is unknown. We aimed to examine the association of sleep disturbances, overall and specific subtypes, with (1) incident and (2) prevalent MCR in older adults. Community-residing adults aged 65 years and older without dementia were recruited from population lists and included in Central Control of Mobility and Aging, a prospective cohort study, in Albert Einstein College of Medicine, Bronx, NY. We included participants with available data for MCR and Pittsburgh Sleep Quality Index (PSQI). MCR was defined as cognitive complaints reported on standardized questionnaires and slow gait speed as recorded on an electronic treadmill and was adjudicated at baseline and annual follow-up visits. Participants were divided into "good" sleepers (≤5) and "poor" sleepers (>5) based on an established PSQI cut score. Among participants without MCR at baseline, Cox proportional hazard models adjusted for (1) age, sex, and education and (2) further for comorbidity index, Geriatric Depression Scale score, and global cognitive score were used to examine the association of baseline sleep disturbances with MCR incidence. Association between poor sleep quality and prevalent MCR at baseline in the overall population was explored using multivariate logistic regression analysis. 445 participants were included (56.9% women, mean age: 75.9 years [75.3; 76.5]). In MCR-free participants at baseline (n = 403), 36 developed incident MCR over a mean follow-up of 2.9 years. Poor sleepers had a higher risk of incident MCR (HR = 2.7 [1.2; 5.2]) compared with good sleepers, but this association was not significant after adjustment for depressive symptoms (adjusted hazard ratio [aHR] = 1.6 [0.7-3.4]). Among the 7 PSQI components, only sleep-related daytime dysfunction (excessive sleepiness and lower enthusiasm) showed a significant risk of MCR in fully adjusted models (aHR = 3.3 [1.5-7.4]). Prevalent MCR was not associated with poor sleep quality (OR [95% CI] = 1.1 [0.5-2.3]). Overall poor sleep quality was associated with incident MCR, but not with prevalent MCR. Specifically, older adults with sleep-related daytime dysfunction are at increased risk of developing MCR. Further studies are needed to validate mechanisms of this relationship.

Utilization, Workflow, and Outcomes of Endovascular Thrombectomy in Patients With vs Without Premorbid Disability in a National Registry.

Given the paucity of high-quality safety/efficacy data on acute stroke therapies in patients with premorbid disability, they risk being routinely excluded from such therapies. We examined utilization of endovascular thrombectomy (EVT), associated workflow, and poststroke outcomes among patients with vs without premorbid disability. We used national registry data on thrombolysis/EVT for the Czech Republic from 1 January 2016 to 31 December 2020. Premorbid disability was defined as prestroke modified Rankin Scale score (mRS) ≥3. We compared proportions of patients with vs without premorbid disability who received EVT and examined workflow times. We compared ΔmRS-change in mRS from prestroke to 3 months-in patients with vs without premorbid disability, in addition to intracerebral hemorrhage (ICH), mortality, and discharge NIHSS (National Institutes of Health Stroke Scale score), adjusting for age, sex, baseline NIHSS, and comorbidities, and verified using propensity score weighting (PSW) and matching for differences in treatment assignment. We stratified by age group (<65, 65-74, 75-84, ≥85 years) to explore outcome heterogeneity with vs without premorbid disability. Among 22,405 patients with ischemic stroke who received thrombolysis/EVT/both, 1,712 (7.6%) had prestroke mRS ≥ 3. Patients with prestroke disability were less likely to receive EVT vs those without (10.1% vs 20.7%, aOR: 0.30, 95% CI 0.24-0.36). When treated, they had longer door-to-arterial puncture times (median: 75 minutes, IQR: 58-100 vs 54, IQR: 27-77, adjusted difference: 12.5, 95% CI 2.68-22.3). Patients with prestroke disability receiving thrombolysis/EVT/both had worse ΔmRS (adjusted rate ratio, aIRR on PSW: 1.57, 95% CI 1.43-1.72), rates of 3-month mRS 5-6, discharge NIHSS, and mortality (aOR-PSW [mortality]: 2.54, 95% CI 1.92-3.34), while ICH did not significantly differ. 32.1% of patients with prestroke disability receiving thrombolysis/EVT/both successfully returned to prestroke state, but this proportion ranged from 19.6% for those older than 85 years to 66.0% for those younger than 65 years. Regardless of premorbid disability, EVT was associated with better outcomes including lower ΔmRS (aIRR-PSW: 0.87, 95% CI 0.83-0.91) and mortality, with no interaction of treatment effect by premorbid disability status (e.g., mortality pinteraction = 0.73). EVT recipients with premorbid disability did not differ significantly for several outcomes including ΔmRS (aIRR: 0.99, 95% CI 0.84-1.17) but were more likely to have 3-month mRS 5-6 (70.1% vs 39.5% without premorbid disability, aOR: 1.85, 95% CI 1.12-3.04). Patients with premorbid disability were less likely to receive EVT, had slower treatment times, and had worse outcomes compared with patients without premorbid disability. However, regardless of premorbid disability, patients fared better with EVT vs medical management and one-third with prestroke disability returned to their prestroke status.

Online Mindfulness-Based Intervention (eMBI) in management of dyspnea in patients with interstitial lung disease: A randomized clinical trial

Dyspnea and cough are frequent symptoms in ILD patients. The management of these symptoms is challenging, and evidence-based therapies are lacking. To evaluate the effect of an online Mindfulness-Based Intervention (eMBI) on reducing dyspnea in patients affected by different ILDs. This study was a prospective, open-label, controlled trial that included patients ≥18 years and a modified Medical Research Council (mMRC) dyspnea scale score of ≥ 1. Patients were randomized into either the eMBI or the control group (CG) for 8 weeks. The primary outcome was the change in the dyspnea mMRC scale. The Leicester Cough Questionnaire (LCQ), King's Brief Interstitial Lung Disease (K-BILD) questionnaire, and Depression, Anxiety, and Stress Scale (DASS-21) were performed before and after the eight weeks. All analyses were conducted on an intention-to-treat basis. The study was registered at the Brazilian Registry of Clinical Trials (ReBEC), RBR-3s4mf9y. 24 patients in the eMBI and 25 in the CG completed the intervention. In the eMBI group, compared to the control group, there was a greater proportion of patients with a reduction in dyspnea according to the mMRC scale score (48.9 % versus,15.4 %, p = 0.001). There was no significant difference between the groups in the LCQ (p = 0.666), or in the K-BILD (p = 0.108), depression (p = 0.08), or anxiety (p = 0.869 or stress (p = 0.789). No moderate or severe adverse events were observed in either group. Eight weeks eMBI is a potentially viable and safe approach, that can help manage dyspnea in ILD patients.

Effects of White Noise and Therapeutic Touch on Pain and Comfort in Newborns during Heel Lance: A Randomized Controlled Study.

Nonpharmacological methods such as white noise and therapeutic touch can be used in pain management in neonates. This randomized controlled study evaluated the effects of white noise and therapeutic touch during heel lance procedures on pain, comfort levels, and physiological parameters in healthy neonates. This parallel, randomized controlled study was conducted in the Obstetrics and Gynecology Service of a regional hospital. The sample comprised 160 neonates with gestational ages of >35weeks randomly assigned to 4 groups (white noise [WN], therapeutic touch [TT], white noise+therapeutic touch [WT], and control [CG] group). Pain and comfort levels were evaluated according to the Neonatal Infant Pain Scale, and the COMFORTneo Scale. The primary outcomes were pain and comfort levels, and the secondary outcomes were heart rate and SpO2 levels. The Kruskal-Wallis test was used to compare the scale scores among groups. There were significant differences among groups in terms of Neonatal Infant Pain Scale and COMFORTneo scores (P <.05). The pain scores for the white noise, therapeutic touch, and white noise+therapeutic touch groups were 4.2±2.0, 5.2±1.6, and 3.3±1.7, respectively. There was a significant difference in average heart rate during the heel lance procedure among the groups (P <.05). Pain scores of the intervention groups were lower compared to the control group. The combination of white noise and therapeutic touch was more effective in reducing pain and increasing comfort levels. Nurses could reduce procedural pain by applying these pain relief methods.

Early pain findings in infants with brachial plexus birth injury: Relationship with function and comorbidities, and cut-off point for fractures

BackgroundInfants with birth brachial plexus injury (BPBI) may have various comorbidities such as fractures, torticollis, plagiocephaly, central nervous system disorders. In infants with BPBI, it is important to identify fractures, which are common among comorbidities, objectively assess pain, and investigate factors that may be associated with pain. AimThe aim of this study is to determine the pain level, comorbidities, and motor function in infants with BPBI and to examine the relationship between these parameters. The second aim is to determine the cut-off value of the pain score that may be a sign of fracture in patients with BPBI, in order to suspect and predict a fracture in the shoulder region and to request additional examinations. Subjects and measurements59 infants with BPBI aged 15–90 days were included in the study. Comorbidities, active joint movements, and total upper extremity function assessed with the Active Movement Scale and pain scores measured with the FLACC Pain Scale were retrospectively analyzed. In addition, pain, comorbidities and motor function were investigated according to types of Narakas, which indicates the degree of nerve injury. ResultsOf the 59 participants, 18 (30.5 %) had at least one comorbidity and 12 (20.3 %) had fractures. The number of comorbidities (p = 0.41), the number of fractures (p = 0.84), and the level of pain (p = 0.71) did not differ by types of Narakas. There was a moderate negative correlation between pain level and upper extremity motor function in upper trunk injuries (p < 0.5, −0.67 < r < −0.46). There was a difference in pain level measured by palpation (p < 0.01) and passive joint movement (p < 0.01) in infants with and without comorbidities. To suspect a fracture in the shoulder region and to request further evaluation, the cut-off value of the Flacc pain level, which may predict a fracture, was 3.5 points for palpation and passive shoulder abduction and 4.5 points for passive external rotation. ConclusionThis is the first study in the BPBI to measure pain in infants using a quantifiable and widely used assessment. Pain level was ranked from high to low as infants with fractures, infants with comorbidities other than fractures and infants without comorbidities. Increased pain adversely affects motor function and pain above the cut-off values is a predictor of fracture.

Samelisant (SUVN-G3031), A Histamine 3 Receptor Inverse Agonist: Results from The Phase 2 Double-Blind Randomized Placebo-Controlled Study for The Treatment of Excessive Daytime Sleepiness in Adult Patients with Narcolepsy

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5% patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

Assessment of traumatic brain injury treatment guided by continuous monitoring of intracranial pressure and brain tissue oxygen partial pressure: A single-center pilot study

Severe traumatic brain injury (TBI) is a leading cause of death and disability. Monitoring intracranial pressure (ICP) is recommended, but the data on the outcomes are conflicting. Adding continuous brain tissue oxygen partial pressure (PbtO2) monitoring may have some benefit but the OXY-TC suggested it did not improve 6-month neurological outcomes. This single-center pilot randomized controlled study aimed to evaluate whether adding PbtO2 monitoring was feasible and could improve the prognosis of severe TBI. The participants were randomized into either an ICP alone or an ICP + PbtO2 group for 7 days, with treatment protocols based on existing guidelines. Clinical parameters were collected hourly. The primary outcome was the feasibility of using PbtO2 monitoring. The secondary outcomes were 6-month survival, analyzed by the log-rank test, the 3- and 6-month Glasgow Outcome Scale (GOS) scores, compared between groups by chi-squared test. Seventy patients were included (36 ICP, 34 ICP + PbtO2). The ICP + PbtO2 group had lower mean daily ICP (13.4 vs. 18.2 mmHg, P = 0.0024) and higher mean daily cerebral perfusion pressure (82.1 vs. 74.5 mmHg, P = 0.0055). The ICP + PbtO2 group had higher 6-month survival (79.4 % vs. 55.6 %, P = 0.0337) and more favorable outcomes at 3 months (67.6 % vs. 38.9 %, P = 0.0160) and 6 months (70.6 % vs. 41.7 %, P = 0.0149). Adding PbtO2 monitoring to ICP monitoring is feasible in patients with severe TBI and could maybe improve the intermediate-term outcomes. The results will serve to design larger trials.

Traditional Thai Massage Steps Development in Acute Ischemic Stroke Patients

Stroke results in many survivors experiencing limb dysfunction and functional disability. Early rehabilitation has shown promise in improving recovery. Traditional Thai Massage (TTM) is noted for potential benefits in aiding stroke recovery. Chaophya Abhaibhubejhr Hospital in Thailand has integrated TTM in treating various diseases and has developed a specialized TTM protocol for acute stroke patients. We develop 23 unique Traditional Thai Massage Steps based on Chaophya Abhaibhubejhr Hospital Experience and assess the feasibility and safety of combining TTM steps with physical therapy (PT) in treating acute ischemic stroke compared to PT alone. 33 stroke patients were randomized into two groups: intervention (TTM + PT) and control (PT alone). The outcomes were improvements in daily living, quality of life, and acute stroke severity by using a modified Rankin Scale (mRS) score, Barthel index of activities of daily living (BI), National Institutes of Health Stroke Scale (NIHSS), and the Stroke Specific Quality Of Life scale (SS-QOL). Both groups significantly improved outcomes over the 20-day study. However, there were no significant differences between the two groups in these measures. Both groups also reported no adverse effects from the treatments.•The 23 unique Traditional Thai Massage Steps for acute ischemic stroke based on Chaophya Abhaibhubejhr Hospital Experience are developed.•TTM protocols for acute ischemic stroke are practical and approved by well-trained Traditional Thai Medicine Practitioners.•Although TTM protocols do not show additional benefits to conventional PT at day 20 after treatment, their combinations for patients with acute ischemic stroke appear safe and feasible.

MELATONIN ON SLEEP IN PARKINSON’S DISEASE: A RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL

BackgroundSleep disturbances are one of the most common non-motor symptoms in Idiopathic Parkinson’s Disease (IPD) patients. However, the effect of melatonin on sleep problems in Parkinson's disease patients is unclear. Aims and objectivesTo study the effect of melatonin on sleep in IPD patients through subjective and objective assessment. MethodsBetween August 2023 to February 2024, we conducted a randomized, double-blind, placebo-controlled trial on IPD patients. We randomized eligible subjects to melatonin (3mg) (n=43) or placebo (n=43) for 8 weeks. The primary endpoint was sleep quality assessed through the Pittsburgh sleep quality index and daytime sleepiness using Epworth sleepiness scale. Secondary endpoints were polysomnographic sleep parameters, quality of life, motor and non-motor symptoms. Assessments were done at baseline and at the end of 8 weeks. ResultsWe screened 107 IPD patients and 86 patients were included in the study. Seventy three patients (melatonin, 35 and placebo, 38) completed the study. The mean change in Pittsburgh Sleep Quality Index (PSQI) score between the two groups was 1.87 (95% CI: 1.5–2.1; p = 0.001) and Epworth Sleepiness Scale (ESS) score was 1.25 (95% CI: 0.80-1.71; p = 0.001) favoring melatonin. The mean difference between the two groups for Non-Motor Symptoms Scale (NMSS) was 6.11 (95% CI 5.27-6.92; p = 0.001), Parkinson's Disease Questionnaire (PDQ 39) 8.12 (95% CI 6.97-9.50; p = 0.001) & Polysomnography (PSG) parameters [sleep latency 8.36 (95% CI 4.38-12.34; p = 0.001) and total sleep time 14.51 (95% CI 5.00-24.41; p = 0.005)] favoring melatonin. Side effects attributable to melatonin were minimal. ConclusionMelatonin is an effective and safe treatment option for sleep problems in PD patients, and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life. We need to emphasize the fact that though we had statistically significant changes in our outcomes, it is not clear whether such changes would have real-life impact (meaningfulness) that would be relevant to licensing authorities or management as patients in our study are young, have short disease duration, have high use of anticholinergics and on modest levodopa equivalent dose. So, we are doubtful if this could be generalized to the typical PD population who are older, have longer disease duration and are on potentially sedating medications or not.

Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis.

Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA. In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity. In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%. Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice. ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.

“Scarfrodesis”—Simultaneously Addressing Hallux Valgus and Hallux Rigidus With a Scarf Osteotomy and First Metatarsophalangeal Joint Arthrodesis: A Case Report

This case report described a novel procedure used to address a concomitant hallux valgus and hallux rigidus in a patient in her sixties with rheumatoid arthritis. Initial radiographs confirmed concomitant severe hallux valgus deformity with first metatarsophalangeal joint osteoarthritis. A scarf osteotomy was performed followed by a first metatarsophalangeal joint arthrodesis in what the authors have called a “Scarfrodesis” procedure. At 1-, 2-, and 3-year follow-ups, the patient had complete resolution of pain, no limitation in mobility, and had complete consolidation of her arthrodesis. Her AOFAS Hallux Metatarsophalangeal-Interphalangeal Scale Score improved from 29 preoperatively to 72 at 1-year and 3-year follow-ups, with improvement in her Visual Analog Scale and SF-36 at 3-year follow-up. The authors advocate the use of this simple but elegant procedure, which has not been described in addressing the dual pathology in this cohort.

West Nile virus encephalitis: Clinical characteristics and a comparison to other infectious encephalitides

PurposeTo compare functional outcomes and help differentiate between important causative agents of acute infectious encephalitis in adults, focusing on West Nile virus encephalitis (WNVE). MethodsThe electronic database of the Tel Aviv Medical Center was screened for patients admitted during 2010–2020 with acute encephalitis. Additionally, patient laboratory results during the same period were screened for CSF samples positive for common pathogens causing encephalitis. The main patient groups were compared in terms of clinical characteristics and functional outcomes. ResultsOne hundred and five infectious encephalitis patients were identified. WNVE patients (n = 31) and VZV encephalitis (VZVE) patients (n = 31) were older than HSV1 encephalitis (HSV1E) patients (n = 15) (median ages 73, 76, 51, respectively). WNVE patients had a more prominent inflammatory profile. CSF characteristics significantly differed between groups, with an extreme mononuclear white blood cell predominance in VZVE patients (median 98 %).Functional outcomes at discharge were significantly worse in WNVE patients (median modified Rankin Scale score 4 at hospital discharge, 2.5 at last follow-up) when compared with HSV1E patients (2.5, 1, respectively) and VZVE patients (1.5, 1, respectively). ConclusionIn odds with previous reports, WNVE and VZVE in this study were far more prevalent than HSV1E. Differences in clinical characteristics could prove clinically useful early in encephalitis, including an association of WNVE with a relatively prominent inflammatory profile (somewhat resembling a bacterial infection) and an extreme mononuclear white blood cell predominance in VZVE. The detrimental outcome of WNVE emphasizes the need to advance research on WNV infection.

Dry Needling Plus Cervical Interlaminar Epidural Steroid Injections: Do We Have More Favorable Results in Cervical Disc Herniation? A Randomized Sham-Controlled Clinical Study

Objective Trigger point-related myofascial pain commonly accompanies cervical disc herniation. The aim of the study is to investigate the effect of dry needling for accompanying trigger points on cervical interlaminar epidural steroid injection treatment outcomes. Design Among the patients scheduled for interlaminar epidural steroid injection for cervical disc herniation, those with active trigger points were randomly divided into three groups: interlaminar epidural steroid injection + dry needling, interlaminar epidural steroid injection + sham dry needling, and only interlaminar epidural steroid injection group. Outcome measures were determined as the change in Numeric Rating Scale, number of active trigger points, and the pressure-pain threshold measurement. Results A total of 66 patients, 22 per group, were included in the final evaluation. While significant decrease in Numeric Rating Scale scores was observed in all three groups at 3rd week and 3rd month, this decrease was significantly more pronounced in the interlaminar epidural steroid injection + dry needling group (P &lt; 0.001). There was a significant decrease in the number of active trigger points in all three groups (P &lt; 0.001). While a significant increase was observed in the pressure-pain threshold value only in the interlaminar epidural steroid injection + dry needling group at the 3rd week, this increase was found to be significant in all three groups at the 3rd month (P &lt; 0.001). Conclusions Combination therapy with dry needling has superiority to interlaminar epidural steroid injection + sham dry needling and only interlaminar epidural steroid injection groups in reducing pain and increasing pressure-pain threshold values.

Therapeutic Interventions to Improve Static Balance in Type 2 DiabetesMellitus: A Systematic Review and Meta-Analysis.

Diabetes mellitus (DM) is a metabolic disorder characterized by an abnormal increase in blood glucose levels resulting from insulin secretion and/or dysfunctional activity that can lead to several serious complications in addition to decreased postural balance. This study aimed to identify and analyze the main interventions used to improve static balance in patients with DM. For the selection of articles, a bibliographic search was performed using PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Only clinical trials that investigated the effect of training on static balance in adults with type 2 DM were selected, and 34 studies were included. The search resulted in the identification of 2681 articles, and of these, 31 were eligible for the study. The identified interventions were proprioceptive, aerobic, resistance training on platforms, in virtual reality, and Tai Chi. The main results obtained were an increase in time in the one-leg stance, Romberg test, and tandem position, a significant increase in the Berg Balance Scale score and balance index, and a reduction in the variables of postural sway. There are a variety of effective training methods for improving static balance, and the choice of intervention to be applied goes beyond proven effectiveness, depending on reproducibility and/or financial cost.

BrainPath Tubular Retractor System for Subcortical Hemorrhagic Vascular Lesions: A Case Series of Technique and Outcomes

BACKGROUND AND OBJECTIVES: Hemorrhagic subcortical vascular lesions such as cavernous malformations (CM) and arteriovenous malformations (AVM) can be neurologically devastating. Conventional open surgical resection is often associated with additional morbidity. The BrainPath® (NICO Corp.) transsulcal tubular retractor system offers a less-invasive corridor to deep-seated lesions. Our objective was to describe a single-center experience with the resection of subcortical hemorrhagic vascular lesions in adult and pediatric patients using the BrainPath® system. METHODS: The departmental database was queried for patients who underwent resection of a hemorrhagic CM, AVM, or cerebral aneurysm through the BrainPath® tubular retractor system between January 2017 and September 2021. All patients underwent either postoperative MRI (for patients with CM) or digital subtraction angiography (for patients with AVM or aneurysm). Demographic and clinical characteristics, preoperative and postoperative imaging features, operative details, and surgical and clinical outcomes were extracted through a retrospective review of the medical records. RESULTS: Fourteen patients (mean [SD] age 32.3 [23.9] years; 7 (50%) female) underwent BrainPath®-based resection of a deeply seated CM (n = 7), AVM (n = 6), or ruptured cerebral aneurysm (n = 1). The mean maximal lesion diameter was 21.5 (12.6) mm. The mean operative time was 134 (53) minutes. Residual lesion was present in 2 patients, both of which underwent repeat BrainPath®-assisted surgery for complete resection. All lesions were completely resected or obliterated on postoperative MRI or digital subtraction angiography. At a mean follow-up of 4.1 (1.1) years, the median modified Rankin Scale score was 1 (range 0-6). CONCLUSION: In a well-selected cohort, we show the effective use of BrainPath® tubular retractors for resection or obliteration of subcortical hemorrhagic vascular lesions. This report further exemplifies the expanded role of the endoport system beyond that of intracerebral hemorrhage and tumor. Further study will elucidate the impact of this less-invasive brain retraction technique on clinical outcome in patients with vascular lesions.

Gastrointestinal cancer surgery in the elderly: The effects of preoperative oral nutritional supplements - A retrospective study.

The current study aimed to explore the effect of nutritional prehabilitation on the clinical prognosis of elderly patients undergoing abdominal cancer surgery. A retrospective study was conducted, where participants were divided into two groups based on whether they received oral nutritional supplementation at the first outpatient visit. The nutritional prehabilitation group (n=41) adopted a nutritional prehabilitation mode (a standard energy intake of 25-30 kcal/kg· d was recommended). While the control group (n=55) received routine care. All patients underwent laparoscopic surgery according to the National Comprehensive Cancer Network (NCCN) guidelines. Changes in nutritional status, complications, psychological status, symptoms, hospitalization days, and expenditures were compared between the two groups. Both groups of patients experienced weight loss. However, the decline in body weight in the prehabilitation group was less than that in the control group (-1.88 vs. -2.56 kg, p < 0.001). In the comparison of nutritional prehabilitation group and control group, significant improvements were observed in the Hospital Anxiety Scale scores (5 vs. 5, p = 0.01) and MD Anderson Symptom Inventory scores (3 vs. 0, p < 0.001) respectively. The infection rate in the nutritional prehabilitation group was lower than that in the control group (17.1% vs. 36.4%, p = 0.04). Additionally, patients in the nutritional prehabilitation group had significantly fewer hospitalization days at discharge (14.3 vs. 17.1 days, p = 0.03). In elderly patients undergoing abdominal cancer surgery, a nutritional prehabilitation model may help maintain better physical and mental status, reduce infection rates, and shorten hospitalization days.