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Administration of Intravenous Dexmedetomidine and Acetaminophen for Improved Postoperative Pain Management in Primary Palatoplasty

J Craniofac Surg. 2021 Nov 2. doi: 10.1097/SCS.0000000000008353. Online ahead of print.

ABSTRACT

OBJECTIVE: Suboptimal pain management after primary palatoplasty (PP) may lead to complications such as hypoxemia, and increased hospital length of stay. Opioids are the first option for postoperative acute pain control after PP; however, adverse effects include excessive sedation, respiratory depression, and death, among others. Thus, optimizing postoperative pain control using opioid-sparing techniques is critically important. This paper aims to analyze efficacy and safety of combined intravenous (IV), dexmedetomidine, and IV acetaminophen during PP.

METHODS: Review of a cohort of patients who underwent PP from April 2009 to July 2018 at a large free-standing children’s hospital was performed, comparing patients who received combined IV dexmedetomidine and acetaminophen with those who did not receive either of the 2 medications. Efficacy was measured through opioid and nonopioid analgesic dose and timing, pain scores, duration to oral intake, and length of stay. Safety was measured by 30-day complication rates including readmission for bleeding and need for supplementary oxygen.

RESULTS: Total postoperative acetaminophen (P = 0.01) and recovery room fentanyl (P < 0.001) requirements were significantly lower in the study group compared with the control group. Length of stay, oral intake duration, pain scores, total postoperative opioid requirements, and complications rates trended favorably in the study group, though differences did not reach statistical significance.

CONCLUSIONS: Intraoperative IV dexmedetomidine and acetaminophen during PP provides safe and effective perioperative pain control, resulting in statistically significant decreased need for postoperative acetaminophen and fentanyl. Larger studies are necessary to determine if other trends identified in this study may be significant.

PMID:34732670 | DOI:10.1097/SCS.0000000000008353

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Effect of Robot-assisted Rehabilitation to Botulinum Toxin A Injection for Upper Limb Disability in Patients with Chronic Stroke: A Case Series and Systematic Review

Neurol Med Chir (Tokyo). 2021 Nov 3. doi: 10.2176/nmc.oa.2020-0408. Online ahead of print.

ABSTRACT

Combining single-joint hybrid assistive limb (HAL-SJ) with botulinum toxin A (BTX-A) therapy is novel and has great therapeutic potential for the rehabilitation of stroke patients with upper limb paralysis. The purpose of this observational case series study was to evaluate the effect of BTX-A and HAL-SJ combination therapy on different exoskeleton robots used for treating upper limb paralysis. The HAL-SJ combination received a BTX-A injection followed by HAL-SJ-assisted rehabilitation for 60 min per session, 10 times per week, during 2 weeks of hospitalization. Clinical evaluations to assess motor function, limb functions used during daily activities, and spasticity were performed prior to injection, at 2-week post-treatment intervention, and at the 4-month follow-up visit. The total Fugl-Meyer assessment-upper limb (FMA-UE), proximal FMA-UE, action research arm test (ARAT), Motor Activity Log (MAL), and Disability Assessment Scale (DAS) showed a statistically significant difference, and a large effect size. However, the FMA distal assessment at 2-week post-treatment intervention showed no significant difference and a moderate effect size. The FMA-UE scores of the extracted systematic review articles showed that our design improved upper limb function. The change in the total FMA-UE score in this study showed that, compared to previous reports in the exoskeletal robotic therapy group, our combination therapy had a higher score than five of the seven references. Our results suggest that BTX-A therapy and HAL-SJ combination therapy may improve upper limb function, similar to other treatment methods in the literature.

PMID:34732591 | DOI:10.2176/nmc.oa.2020-0408

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Comparison of Two Extubation Techniques in Critically Ill Adult Subjects: The ExtubAR Randomized Clinical Trial

Respir Care. 2021 Nov 3:respcare.09276. doi: 10.4187/respcare.09276. Online ahead of print.

ABSTRACT

BACKGROUND: Two orotracheal extubation techniques are described in the literature: the traditional technique and the positive-pressure technique. Although prior studies reported better clinical outcomes with the positive-pressure extubation technique, its superiority has not been extensively studied yet. This study was to determine whether the positive-pressure orotracheal extubation technique, compared with the traditional orotracheal extubation technique, reduces the incidence of major postextubation complications (up to 60 min) in critically ill adult subjects.

METHODS: This was a multi-center randomized clinical trial. Subjects age > 18 y, requiring invasive mechanical ventilation through an endotracheal tube, who met the orotracheal extubation criteria were included and randomized to traditional extubation group (removing the endotracheal tube by applying continuous endotracheal suctioning during the entire procedure) or positive-pressure group (application of pressure support mode at 15/10 cm H2O during cuff deflation and extubation). The primary measure was postextubation major complications, defined as the clinical evidence of at least one of the following: desaturation, upper-airway obstruction, or vomiting.

RESULTS: A total of 725 subjects was randomly assigned to the traditional extubation group (n = 358) and positive-pressure group (n = 367). Seventeen subjects were eliminated and not included in the per-protocol analysis. Of 708 subjects, 185 (26.1%) developed at least one major complication. The incidence was 27.8% (96/345) in the traditional group compared with 24.5% (89/363) in the positive-pressure group. No statistically significant differences were observed between the 2 groups (absolute risk 3% [95 CI -3 to 10]; relative risk, 0.88 [95 CI 0.69-1.13], P = .32).

CONCLUSIONS: Despite the trend toward the positive-pressure group, no statistically significant differences were observed. Our findings agree with the literature in that positive-pressure extubation is a safe procedure; therefore, both techniques may be used during extubation in critically ill adult patients.

PMID:34732586 | DOI:10.4187/respcare.09276

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Clinical Phenotyping of Out-of-Hospital Cardiac Arrest Patients With Shockable Rhythm - Machine Learning-Based Unsupervised Cluster Analysis

Circ J. 2021 Nov 2. doi: 10.1253/circj.CJ-21-0675. Online ahead of print.

ABSTRACT

BACKGROUND: The hypothesis of this study is that latent class analysis could identify the subphenotypes of out-of-hospital cardiac arrest (OHCA) patients associated with the outcomes and allow us to explore heterogeneity in the effects of extracorporeal cardiopulmonary resuscitation (ECPR).Methods and Results:This study was a retrospective analysis of a multicenter prospective observational study (CRITICAL study) of OHCA patients. It included adult OHCA patients with initial shockable rhythm. Patients from 2012 to 2016 (development dataset) were included in the latent class analysis, and those from 2017 (validation dataset) were included for evaluation. The association between subphenotypes and outcomes was investigated. Further, the heterogeneity of the association between ECPR implementation and outcomes was explored. In the study results, a total of 920 patients were included for latent class analysis. Three subphenotypes (Groups 1, 2, and 3) were identified, mainly characterized by the distribution of partial pressure of O2(PO2), partial pressure of CO2(PCO2) value of blood gas assessment, cardiac rhythm on hospital arrival, and estimated glomerular filtration rate. The 30-day survival outcomes were varied across the groups: 15.7% in Group 1; 30.7% in Group 2; and 85.9% in Group 3. Further, the association between ECPR and 30-day survival outcomes by subphenotype groups in the development dataset was as varied. These results were validated using the validation dataset.

CONCLUSIONS: The latent class analysis identified 3 subphenotypes with different survival outcomes and potential heterogeneity in the effects of ECPR.

PMID:34732587 | DOI:10.1253/circj.CJ-21-0675

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Predictive value of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in evaluating both lung involvement and severity of patients with coronavirus disease 2019

Saudi Med J. 2021 Nov;42(11):1223-1228. doi: 10.15537/smj.2021.42.11.20210485.

ABSTRACT

OBJECTIVES: To investigate the relationship of the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) with lung involvement and total lung severity score (TLSS) in computed tomography (CT) of patients with coronavirus disease -19 (COVID-19) and to evaluate their clinical usability.

METHODS: Basic laboratory, clinical features and imaging data of patients was obtained by examining the file and archive records of our hospital. According to the findings of lung CT scan at the time of diagnosis among COVID-19 patients, 2 groups were formed.

RESULTS: The NLR was 2.22±11.15 and the PLR was 142.77±387.10 in patients with COVID-19 pneumonia. The NLR was 1.88±7.47 and the PLR was 130.65±203.6 8 in patients without COVID-19 pneumonia. The differences in the NLR and the PLR were determined to be statistically significant between the 2 groups. A positive correlation was observed between NLR and PLR (r=0.225, p=0.010) and TLSS (r=0.244, p=0.005).

CONCLUSION: This study showed that the NLR and PLR values can be 2 inflammatory markers that can be used to evaluate lung involvement and disease severity in COVID-19 patients. At the time of initial diagnosis and during follow-up, these markers can give an idea in terms of prognosis, together with other clinical findings and markers.

PMID:34732555 | DOI:10.15537/smj.2021.42.11.20210485

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Predictive feedback, early sensory representations and fast responses to predicted stimuli depend on NMDA receptors

J Neurosci. 2021 Nov 2:JN-RM-1311-21. doi: 10.1523/JNEUROSCI.1311-21.2021. Online ahead of print.

ABSTRACT

Learned associations between stimuli allow us to model the world and make predictions, crucial for efficient behavior; e.g., hearing a siren, we expect to see an ambulance and quickly make way. While there are theoretical and computational frameworks for prediction, the circuit and receptor-level mechanisms are unclear. Using high-density EEG, Bayesian modeling and machine learning, we show that inferred “causal” relationships between stimuli and frontal alpha activity account for reaction times (a proxy for predictions) on a trial-by-trial basis in an audio-visual delayed match-to-sample task which elicited predictions. Predictive beta feedback activated sensory representations in advance of predicted stimuli. Low-dose ketamine, a NMDA receptor blocker – but not the control drug dexmedetomidine – perturbed behavioral indices of predictions, their representation in higher-order cortex, feedback to posterior cortex and pre-activation of sensory templates in higher-order sensory cortex. This study suggests predictions depend on alpha activity in higher-order cortex, beta feedback and NMDA receptors, and ketamine blocks access to learned predictive information.SIGNIFICANCE STATEMENT:We learn the statistical regularities around us, creating associations between sensory stimuli. These associations can be exploited by generating predictions, which enable fast and efficient behavior. When predictions are perturbed, it can negatively influence perception and even contribute to psychiatric disorders such as schizophrenia. Here we show that the frontal lobe generates predictions and sends them to posterior brain areas, to activate representations of predicted sensory stimuli before their appearance. Oscillations in neural activity – alpha and beta waves – are vital for these predictive mechanisms. The drug ketamine blocks predictions and the underlying mechanisms. This suggests that the generation of predictions in the frontal lobe, and the feedback pre-activating sensory representations in advance of stimuli, depend on NMDA receptors.

PMID:34732525 | DOI:10.1523/JNEUROSCI.1311-21.2021

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High Gamma Activity in Cortex and Hippocampus is Correlated with Autonomic Tone During Sleep

eNeuro. 2021 Nov 2:ENEURO.0194-21.2021. doi: 10.1523/ENEURO.0194-21.2021. Online ahead of print.

ABSTRACT

Studies in animals have demonstrated a strong relationship between cortical and hippocampal activity, and autonomic tone. However, the extent, distribution, and nature of this relationship have not been investigated with intracranial recordings in humans during sleep. Cortical and hippocampal population neuronal firing was estimated from high gamma band activity (HG) from 70 to 110 Hz in local field potentials recorded from 15 subjects (9 females) during non-rapid eye movement (NREM) sleep. Autonomic tone was estimated from heart rate variability (HRV). HG and HRV were significantly correlated in the hippocampus and multiple cortical sites in NREM stages N1-3. The average correlation between HG and HRV could be positive or negative across patients given anatomical location and sleep stage and was most profound in lateral temporal lobe in N3, suggestive of greater cortical activity associated with sympathetic tone. Patient-wide correlation was related to delta band activity (1-4 Hz), which is known to be correlated with high gamma activity during sleep. The percentage of statistically correlated channels was weaker in N1 and N2 as compared to N3, and was strongest in regions that have previously been associated with autonomic processes, such as anterior hippocampus and insula. The anatomical distribution of HRV-HG correlations during sleep did not reproduce those usually observed with PET or fMRI during waking. This study aims to characterize the relationship between autonomic tone and neuronal firing rate during sleep and further studies are needed to investigate finer temporal resolutions, denser coverages, and different frequency bands in both waking and sleep.Significance StatementStudies in animals have shown that the autonomic nervous system sets the operating mode of all the organ systems in the body, including the central nervous system. We show here that high gamma activity in widespread cortical and hippocampal regions is correlated with heart rate variability in humans during sleep. The correlation was especially profound in sites which have previously been associated with autonomic and emotional regulation. The direction of change varied between forebrain locations, indicating the existence of sympathetic and parasympathetic modulating structures. The percentage of correlated channels between autonomic tone and cortical activity was greatest in the deepest stages of slow-wave sleep. Overall, this study characterizes in humans a foundational link in the unity of mind and body.

PMID:34732536 | DOI:10.1523/ENEURO.0194-21.2021

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Manual QT interval measurement with a smartphone-operated single-lead ECG versus 12-lead ECG: a within-patient diagnostic validation study in primary care

BMJ Open. 2021 Nov 3;11(11):e055072. doi: 10.1136/bmjopen-2021-055072.

ABSTRACT

OBJECTIVE: To determine the accuracy of QT measurement in a smartphone-operated, single-lead ECG (1L-ECG) device (AliveCor KardiaMobile 1L).

DESIGN: Cross-sectional, within-patient diagnostic validation study.

SETTING/PARTICIPANTS: Patients underwent a 12-lead ECG (12L-ECG) for any non-acute indication in primary care, April 2017-July 2018.

INTERVENTION: Simultaneous recording of 1L-ECGs and 12L-ECGs with blinded manual QT assessment. OUTCOMES OF INTEREST: (1) Difference in QT interval in milliseconds (ms) between the devices; (2) measurement agreement between the devices (excellent agreement <20 ms and clinically acceptable agreement <40 ms absolute difference); (3) sensitivity and specificity for detection of extreme QTc (short (≤340 ms) or long (≥480 ms)), on 1L-ECGs versus 12L-ECGs as reference standard. In case of significant discrepancy between lead I/II of 12L-ECGs and 1L-ECGs, we developed a correction tool by adding the difference between QT measurements of 12L-ECG and 1L-ECGs.

RESULTS: 250 ECGs of 125 patients were included. The mean QTc interval, using Bazett’s formula (QTcB), was 393±25 ms (mean±SD) in 1L-ECGs and 392±27 ms in lead I of 12L-ECGs, a mean difference of 1±21 ms, which was not statistically different (paired t-test (p=0.51) and Bland Altman method (p=0.23)). In terms of agreement between 1L-ECGs and lead I, QTcB had excellent agreement in 66.9% and clinically acceptable agreement in 93.4% of observations. The sensitivity and specificity of detecting extreme QTc were 0% and 99.2%, respectively. The comparison of 1L-ECG QTcB with lead II of 12L-ECGs showed a significant difference (p=<0.01), but when using a correction factor (+9 ms) this difference was cancelled (paired t-test (p=0.43) or Bland Altman test (p=0.57)). Moreover, it led to improved rates of excellent (71.3%) and clinically acceptable (94.3%) agreement.

CONCLUSION: Smartphone-operated 1L-ECGs can be used to accurately measure the QTc interval compared with simultaneously obtained 12L-ECGs in a primary care population. This may provide an opportunity for monitoring the effects of potential QTc-prolonging medications.

PMID:34732504 | DOI:10.1136/bmjopen-2021-055072

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Effect of preoperative duloxetine treatment on postoperative chronic residual pain after total hip or knee arthroplasty: a randomised controlled trial

BMJ Open. 2021 Nov 3;11(11):e052944. doi: 10.1136/bmjopen-2021-052944.

ABSTRACT

OBJECTIVES: A key predictor for developing chronic residual pain after total knee or hip arthroplasty (TKA/THA) is sensitisation. Sensitisation can be defined as an ‘increased responsiveness of nociceptive neurons in the nervous system’. Aim of this study is to investigate the effects of preoperative treatment with duloxetine in sensitised knee and hip osteoarthritis (OA) patients on postoperative chronic residual pain up to 1 year after arthroplasty.

SETTING: A multicentre, pragmatic, prospective, randomised clinical trial was conducted in three secondary care hospitals in the Netherlands.

PARTICIPANTS: Patients with primary knee/hip OA who were planned for TKA/THA were screened using the modified painDETECT Questionnaire. Patients whose painDETECT score indicated that sensitisation may be present were eligible for participation. 111 participants were included and randomly assigned 1:1 to an intervention or control group. The intervention group received additional duloxetine treatment, the control group did not receive any additional treatment but was allowed to continue with any pain medication they were already taking.

INTERVENTIONS: Preoperative oral treatment for 7 weeks with 60 mg/day of duloxetine was compared with usual care.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was pain at 6 months after arthroplasty, assessed with the Pain Subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS) with a 0-100 scale. Secondary outcome measures were Visual Analogue Scale (VAS), and neuropathic-like pain measured using the modified PainDETECT Questionnaire. Longitudinal data collection included time points directly after duloxetine treatment, 1-day preoperatively, and 6 weeks, 6 months and 12 months postoperatively.

RESULTS: Mean improvement in the KOOS/HOOS pain subscale at 6 months postoperatively was 37 (SD 28.1) in the intervention group and 43 (SD 26.5) in the control group. No statistically significant difference was found in change score 6 months postoperatively between the two groups (p=0.280). 12 patients from the intervention group (21%) discontinued duloxetine due to adverse effects.

CONCLUSIONS: Preoperative targeted treatment with duloxetine in end-stage knee and hip OA patients with sensitisation does not influence postoperative chronic residual pain after TKA/THA.

TRIAL REGISTRATION NUMBER: NTR4744.

PMID:34732491 | DOI:10.1136/bmjopen-2021-052944

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Does knowledge of liver fibrosis affect high-risk drinking behaviour (KLIFAD)? protocol for a feasibility randomised controlled trial

BMJ Open. 2021 Nov 3;11(11):e054954. doi: 10.1136/bmjopen-2021-054954.

ABSTRACT

INTRODUCTION: Heavy drinkers in contact with alcohol services do not routinely have access to testing to establish the severity of potential liver disease. Transient elastography by FibroScan can provide this information. A recent systematic review suggested providing feedback to patients based on markers of liver injury can be an effective way to reduce harmful alcohol intake. This randomised control trial (RCT) aims to establish the feasibility of conducting a larger national trial to test the effectiveness of FibroScan advice and Alcohol Recovery Video Stories (ARVS) in changing high-risk drinking behaviour in community alcohol services common to UK practice.

METHODS AND ANALYSIS: This feasibility trial consists of three work packages (WP). WP1: To draft a standardised script for FibroScan operators to deliver liver disease-specific advice to eligible participants having FibroScan. WP2: To create a video library of ARVS for use in the feasibility RCT (WP3). WP3: To test the feasibility of the trial design, including the FibroScan script and video stories developed in WP1 and WP2 in a one-to-one individual randomised trial in community alcohol services. Semi-structured interviews will be conducted at 6 months follow-up for qualitative evaluation. Outcomes will be measures of the feasibility of conducting a larger RCT. These outcomes will relate to: participant recruitment and follow-up, intervention delivery, including the use of the Knowledge of LIver Fibrosis Affects Drinking trial FibroScan scripts and videos, clinical outcomes, and the acceptability and experience of the intervention and trial-related procedures. Data analysis will primarily be descriptive to address the feasibility aims of the trial. All proposed analyses will be documented in a Statistical Analysis Plan.

ETHICS AND DISSEMINATION: This trial received favourable ethical approval from the West of Scotland Research Ethics Service (WoSRES) on 20 January 2021, REC reference: 20/WS/0179. Results will be submitted for publication to a peer-reviewed journal.

TRIAL REGISTRATION NUMBER: ISRCTN16922410.

PMID:34732502 | DOI:10.1136/bmjopen-2021-054954