Intensive Protocol Research Articles

G.O.O.S.E.: Introducing a novel five‐stage structured framework for the early phases of teaching and learning ultrasound

AbstractThe sonography profession faces a critical global workforce shortage, particularly pronounced in Australia, due to insufficient clinical training opportunities and an ageing workforce. The financial burden and increased scan times associated with training exacerbate this issue. Innovative approaches, such as intensive ultrasound courses and pair scanning protocols, have shown promise in addressing these challenges. The GOOSE framework (Get the window, Optimise the view, Optimise the image, Select the image, Explain the findings) offers a structured, step‐by‐step approach to practical sonography training. This framework deconstructs complex ultrasound skills into manageable tasks, optimises cognitive load management, and provides explicit guidance for novice learners. The GOOSE framework is designed to enhance the efficiency of teaching and learning by simplifying complex skills into clear, actionable steps, supported by checklists that guide both instructors and students through the training process. The GOOSE framework offers a systematisation of knowledge transfer that, combined with deliberate practice and structured feedback, ensures learners progressively build their skills with focused, goal‐directed activities. While this model is yet to be validated, initial implementations have shown promising results in improving trainee performance, reducing supervision workload, and standardising instructional methods. This article outlines the principles of the GOOSE framework, its development, and its application in a specialised training facility, proposing it as a standardised model to enhance practical ultrasound education and improve teaching and learning efficiency.

A field comparison study of two vaccine protocols against Erysipelothrix rhusiopathiae in two types of swine breeds in Spain

Erysipelas still causes large economic losses to pig industry. Maternal immunity is critical to prevent erysipelas in young animals, thus, intensive vaccination protocols or practices focused on the improvement of the maternally derived immunity could provide substantial benefits. The present study evaluates potential changes in antibodies levels in sows and their offspring using two types of tests (commercial ELISA, Ingenasa or rSpaA415 ELISA) when two different vaccination programs (before farrowing or after farrowing) against Erysipelothrix rhusiopathiae were applied to sows from Iberian (A) or conventional Large White-Landrace (B) pig farms. The results showed a statistical correlation between titers found in sows and their one-week old piglets in both tests. The overall mean of (log) antibody titers in farm B measured by the commercial ELISA test was significantly higher in pre-farrowing vaccinated sows compared to the post-farrowing vaccine protocol (p = 0.0278). Additionally, using the rSpaA415 ELISA test, the overall mean of (log) antibody titers was significantly higher in pre-farrowing sows (p = 0.0056) compared to sows following post-farrowing vaccine protocol (p = 0.0003) or non- vaccinated sows. None of the above-mentioned differences were found in farm A. The overall mean of (log) antibody titers in piglets from the pre-farrowing vaccination protocol was significantly higher than piglets from the post-farrowing vaccination protocol in farm A (p = 0.0059; rSpaA415 ELISA) and farm B (p = 0.0168 and p = 0.0098 for the commercial and rSpaA415 ELISA data, respectively). Additionally, higher proportion of piglets from pre-farrowing vaccinated sows remained seropositive during the post-weaning period (days 42 to 84) compared to piglets from non-vaccinated or post-farrowing vaccinated groups in both farms A and B.

A randomised controlled phase II trial to examine the feasibility of using hyper-oxygenated fatty acids (HOFA) to prevent facial pressure injuries from medical devices among adults admitted to intensive care-A research protocol.

One in three patients admitted to intensive care will sustain a pressure injury (PI) from a medical device. These injuries are painful and when on the face, head or neck they can result in permanent disfigurement. Preliminary evidence of the efficacy of hyper-oxygenated fatty acids (HOFAs) to prevent facial pressure injuries from medical devices is promising; however, the feasibility of incorporating HOFAs into current standard care to prevent PI from a medical device of the face, head and neck has not been extensively explored. It is intended that the findings from this phase II feasibility study will inform the design of a larger phase III trial, by addressing two primary aims: (1) to assess the feasibility of incorporating HOFAs into standard care to prevent device-related pressure ulcers of the skin associated with the face, head and neck assess the feasibility and (2) efficacy preliminary effectiveness of HOFA. This feasibility study is an investigator-initiated mixed method study incorporating a multi-centre randomised controlled trial of using HOFAs as an adjunct to standard pressure injury prevention and care, compared with standard care alone to prevent facial, head or neck from medical devices among adults admitted to intensive care. The primary outcome of interest is the incidence of facial, head or neck pressure injuries during the first 14 days in intensive care. Secondary outcomes include PI staging, medical device exposure and intensive care and hospital outcomes. The primary analysis will be undertaken using Cox's Proportional Hazards model, and due to the exploratory nature of this phase II trial, efficacy will be based on a one-sided p-value for superiority set at 0.10. Type I and Type II error rates are set at 20%; therefore, a total sample size of 196 study participants is planned. To explore the feasibility of incorporating HOFA into usual care and to design a larger phase III trial, we will aim to interview between 10 and 20 nurses across participating intensive care unit sites. Pressure injuries of the face, head or neck from medical devices, among adults admitted to intensive care, are considered preventable. This phase II study will investigate the feasibility and efficacy of HOFAs as an adjunct to standard care. Importantly, we aim to inform the development of a larger phase III trial.

Clinical Effects of Voice Therapy on Vocal Outcomes in Unilateral Vocal Fold Paralysis: Proof-of-Concept Study for Two SOVT-Based Treatment Protocols

BackgroundStudies on treatment efficacy in unilateral vocal fold paralysis (UVFP) often lack a predetermined treatment protocol, and little is known about the effects of specific vocal techniques on vocal outcomes and quality of life in UVFP patients. The purpose of this preliminary proof of concept study is to investigate the effects and feasibility of two intensive treatment protocols based on water-resistance therapy (WRT) and vocal function exercises (VFE). MethodsTen participants with acute or chronic UVFP/paresis were recruited in the study and randomly assigned to the WRT or VFE group. Three of these participants presented with aphonia and could not complete the program as prescribed. The remaining participants completed an intensive therapy program with the assigned vocal technique. Before, during, and after the program, a multidimensional voice assessment was performed. Maximum phonation time, acoustic, perceptual, and patient-reported outcome measures were obtained. ResultsWRT and VFE had positive clinical effects on instrumental and auditory-perceptual voice quality, glottal closure, and patient-reported outcome measures, but inter-individual variability was high. Studies with larger sample sizes are necessary to confirm or refute these findings. ConclusionThe WRT- and VFE-based therapy programs are both feasible and seem to elicit positive clinical changes in UVFP patients. Suggestions on how to improve the programs are provided, as well as considerations for implementation in clinical practice. Follow-up research is needed to examine the efficacy of both programs on group level.

Venetoclax-based salvage therapy as a bridge to transplant is feasible and effective in patients with relapsed/refractory AML

AbstractThe B-cell lymphoma 2 inhibitor venetoclax (VEN) in combination with hypomethylating agents has been approved for first-line treatment of patients with acute myeloid leukemia (AML) ineligible for intensive treatment. Emerging data suggest that VEN-containing treatment strategies may also be effective in relapsed/refractory (R/R) AML; however, comparative studies with conventional treatment strategies for medically fit patients as a bridge-to-transplant strategy are limited. Using propensity score matching (PSM) analysis, we compared 37 patients with R/R AML, who received VEN-based salvage therapy as bridge to allogeneic hematopoietic cell transplantation (allo-HCT), with 90 patients from the German Study Alliance Leukemia AML registry, who were treated with non–VEN-containing salvage therapy according to their treating physician’s choice (TPC), including intensive and nonintensive protocols. The overall response rate (complete remission [CR] + CR with incomplete hematologic recovery) among all VEN patients was significantly higher than the TPC control cohort (62% vs 42%; P = .049). Overall, 73% of VEN-treated patients vs 63% of TPC patients were successfully bridged to allo-HCT (P = .41). After a median follow-up of 34.3 months for the VEN cohort and 21.0 months for the TPC cohort, the median overall survival (OS) were 15.8 months (95% confidence interval [CI], 10.6 to NE) and 10.5 months (95% CI, 6.8-19.6; P = .15), respectively. PSM revealed a trend toward improved OS for VEN patients (HR, 0.70; 95% CI, 0.41-1.22; P = .20). Median event-free survival was significantly longer in the VEN cohort (8.0 months) than the TPC cohort (3.7 months; P = .006). In summary, our data suggest that VEN-based salvage therapy is a safe and effective bridge to allo-HCT for this difficult-to-treat AML patient population.

Effects of Lower Limb Heat Therapy, Exercise Training, or a Combined Intervention on Vascular Function: A Randomized Controlled Trial.

To compare the effects of 8 weeks of no intervention (CON), lower limb heat therapy (HEAT), moderate-intensity exercise training (EX), or combined training and therapy (HEATEX) in young, healthy recreationally active adults. Sixty participants (23 ± 3 years, 30 females) were randomly allocated into either CON (n = 15), HEAT (n = 15), EX (n = 14), or HEATEX (n = 16). The primary outcome was vascular function, assessed through brachial artery flow-mediated dilation tests (BA FMD). Secondary measures included arterial stiffness (pulse wave velocity, PWV); cardiorespiratory fitness (VO2peak); body composition; and quadriceps muscle strength. There were no differences in BA FMD between the groups before and after the interventions (all p > 0.05). Both interventions with a heating component were associated with within-group reductions in carotid-femoral PWV, and increases in absolute and relative VO2peak after 8 weeks (HEAT: ∆-0.27 [-0.53, -0.02] m/s, ∆0.18 [0.06, 0.29] L/min, ∆2.18 [0.60, 3.76] ml/kg/min, respectively; HEATEX: ∆-0.33 [-0.58, -0.09], ∆0.21 [0.11, 0.32] L/min, ∆2.59 [1.06, 4.12] ml/kg/min, respectively), but no between-group differences were observed (p = 0.25, p = 0.21, and p = 0.55, respectively). There was also a within-group decrease in body fat percentage with EX (∆-1.37 [-2.45, -0.29] %), but no changes in leg strength in any of the groups (p = 0.79). This randomized controlled trial is the first to examine the efficacy of lower limb heating against traditionally prescribed exercise training. In our young cohort, 8 weeks of training and/or therapy was insufficient to improve vascular function. More intense protocols and longer interventions involving lower limb heating may be required to elicit improvements in health outcomes.

Multi-modal, Label-free, Optical Mapping of Cellular Metabolic Function and Oxidative Stress in 3D Engineered Brain Tissue Models.

Brain metabolism is essential for the function of organisms. While established imaging methods provide valuable insights into brain metabolic function, they lack the resolution to capture important metabolic interactions and heterogeneity at the cellular level. Label-free, two-photon excited fluorescence imaging addresses this issue by enabling dynamic metabolic assessments at the single-cell level without manipulations. In this study, we demonstrate the impact of spectral imaging on the development of rigorous intensity and lifetime label-free imaging protocols to assess dynamically over time metabolic function in 3D engineered brain tissue models comprising human induced neural stem cells, astrocytes, and microglia. Specifically, we rely on multi-wavelength spectral imaging to identify the excitation/emission profiles of key cellular fluorophores within human brain cells, including NAD(P)H, LipDH, FAD, and lipofuscin. These enable development of methods to mitigate lipofuscin's overlap with NAD(P)H and flavin autofluorescence to extract reliable optical metabolic function metrics from images acquired at two excitation wavelengths over two emission bands. We present fluorescence intensity and lifetime metrics reporting on redox state, mitochondrial fragmentation, and NAD(P)H binding status in neuronal monoculture and triculture systems, to highlight the functional impact of metabolic interactions between different cell types. Our findings reveal significant metabolic differences between neurons and glial cells, shedding light on metabolic pathway utilization, including the glutathione pathway, OXPHOS, glycolysis, and fatty acid oxidation. Collectively, our studies establish a label-free, non-destructive approach to assess the metabolic function and interactions among different brain cell types relying on endogenous fluorescence and illustrate the complementary nature of information that is gained by combining intensity and lifetime-based images. Such methods can improve understanding of physiological brain function and dysfunction that occurs at the onset of cancers, traumatic injuries and neurodegenerative diseases.

The effect of an intensive lipid-lowering therapy protocol on achieving target LDL-C levels in patients with acute coronary syndrome

The effect of an intensive lipid-lowering therapy protocol on achieving target LDL-C levels in patients with acute coronary syndrome

The Immediate Effects of a Standardized Kettlebell Swing Protocol on Lumbar Paraspinal Muscle Function: A Randomized Controlled Trial.

Hanney, WJ, Perez, A, Collado, G, Palmer, AC, Wilson, AT, Richardson, RM, and Kolber, MJ. J Strength Cond Res XX(X): 000-000, 2024-Kettlebell swings (KBSs) are commonly used to target the lumbar erector spinae and lower body musculature. This exercise exhibits distinct loading properties that requires cyclical contraction of the trunk extensors and posterior chain, potentially explaining its novel influence on muscle contractility. Tensiomyography (TMG) is a reliable, noninvasive, passive technique that may be used to examine muscular fatigue produced by exercises such as KBSs. The purpose of this randomized control trial was to determine the extent of muscle fatigue in the lumbar erector spinae musculature following the performance of a previously published high-intensity interval KBS protocol. Forty-one adults between the ages of 18 and 45 years were recruited. Inclusion criteria included subjects with no recent history of low back pain and clearance by the physical activity readiness questionnaire. Subjects were randomly allocated to either a KBS group (n = 21) or a control group (CON; n = 20) who only performed the unloaded warm-up. Subjects were assessed at baseline, postintervention, and 24-hours postintervention for bilateral erector spinae fatigue, measured by 5 TMG parameters (Dm, Tc, Tr, Td, and Ts). The results were evaluated through a 2 × 3 (group × time) repeated-measures analysis of variance. The level of significance was set at p ≤ 0.05. There was no significant difference in lumbar erector spinae fatigue, measured by the 5 TMG parameters (p ≥ 0.079), following the interval KBS protocol in comparison with the CON group at 3 assessment periods. A high-intensity interval KBS protocol failed to produce significant differences in erector spinae fatigue compared with the control group that did not perform a KBS. These findings warrant further investigation into muscle fatigue produced with higher intensity protocols and possibly suggest, depending on the programming goals, the need for an alternate KBS training parameters.

Compliance and response consistency in a lengthy intensive longitudinal data protocol.

Research on real-world patterns of substance use increasingly involves intensive longitudinal data (ILD) collection, requiring long assessment windows. The present study extends limited prior research examining event- and person-level influences on compliance and response consistency by investigating how these behaviors are sustained over time in an ILD study of alcohol and cannabis co-use in college students. Participants (n = 316) completed two 28-day bursts of ILD comprising five daily surveys, which included a morning survey of prior-day drinking. We used linear mixed effects models in a multilevel interrupted time series framework to evaluate the associations of time and measurement burst with (a) noncompliance (count of missed surveys) and (b) response consistency (difference between same-day report of drinking and morning report of prior-day drinking). We observed that time was positively associated with noncompliance, with no discontinuity associated with measurement burst. The slope of time was more positive in the second burst. Neither time nor measurement burst were significantly associated with consistent reporting. However, survey nonresponse and consistency of responding appeared to be impacted by the same-day use of substances. Overall, compliance decreased while consistency was stable across the duration of a lengthy ILD protocol. Shorter assessment windows or adaptive prompting strategies may improve overall study compliance. Further work examining daily burden and context is needed to inform future ILD design. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Apnoea as a novel method to improve exercise performance: A current state of the literature.

Acute breath-holding (apnoea) induces a spleen contraction leading to a transient increase in haemoglobin concentration. Additionally, the apnoea-induced hypoxia has been shown to lead to an increase in erythropoietin concentration up to 5h after acute breath-holding, suggesting long-term haemoglobin enhancement. Given its potential to improve haemoglobin content, an important determinant for oxygen transport, apnoea has been suggested as a novel training method to improve aerobic performance. This review aims to provide an update on the current state of the literature on this topic. Although the apnoea-induced spleen contraction appears to be effective in improving oxygen uptake kinetics, this does not seem to transfer into immediately improved aerobic performance when apnoea is integrated into a warm-up. Furthermore, only long and intense apnoea protocols in individuals who are experienced in breath-holding show increased erythropoietin and reticulocytes. So far, studies on inexperienced individuals have failed to induce acute changes in erythropoietin concentration following apnoea. As such, apnoea training protocols fail to demonstrate longitudinal changes in haemoglobin mass and aerobic performance. The low hypoxic dose, as evidenced by minor oxygen desaturation, is likely insufficient to elicit a strong erythropoietic response. Apnoea therefore does not seem to be useful for improving aerobic performance. However, variations in apnoea, such as hypoventilation training at low lung volume and repeated-sprint training in hypoxia through short end-expiratory breath-holds, have been shown to induce metabolic adaptations and improve several physical qualities. This shows promise for application of dynamic apnoea in order to improve exercise performance. HIGHLIGHTS: What is the topic of this review? Apnoea is considered as an innovative method to improve performance. This review discusses the effectiveness of apnoea (training) on performance. What advances does it highlight? Although the apnoea-induced spleen contraction and the increase in EPO observed in freedivers seem promising to improve haematological variables both acutely and on the long term, they do not improve exercise performance in an athletic population. However, performing repeated sprints on end-expiratory breath-holds seems promising to improve repeated-sprint capacity.

Acute toxicity of chemotherapy in central nervous system germ cell tumour patients according to age.

SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed. CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs. 296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI. Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.

Effects of Fatigue on Lower Limb Biomechanics and Kinetic Stabilization During the Tuck-Jump Assessment.

General and local muscular fatigue is postulated to negatively alter lower limb biomechanics; however, few prospective studies have been done to examine the effect of fatigue on tuck-jump performance. The tuck-jump assessment (TJA) is a criteria-based visual screening tool designed to identify neuromuscular deficits associated with anterior cruciate ligament (ACL) injury. Use of kinetics during the TJA after an intense sport-specific fatigue protocol may identify fatigue-induced neuromuscular deficits associated with ACL injury risk. To examine the effects of a sport-specific fatigue protocol on visually evidenced (2-dimensional) technical performance of repeated tuck jumps and lower limb kinetic stabilization. Cross-sectional study. Laboratory. Twelve female netball athletes (age = 20.8 ± 2.6 years, height = 170.0 ± 0.04 cm, mass = 67.5 ± 7.4 kg). Participants performed 1 set of a TJA before and after a sport-specific fatigue protocol. Paired t tests and effect sizes were used to evaluate differences and the magnitude of differences in TJA scoring criterion, kinetics, and kinetic stabilization prefatigue to postfatigue. A small increase was observed for vertical relative lower extremity stiffness postfatigue (P = .005; Hedges g = 0.45). Peak center-of-mass displacement, time of jump cycle, ground contact time, flight time, jump height, and vertical net impulse decreased with small to moderate effect sizes (P < .01; Hedges g range, 0.41-0.74). No differences were observed for TJA composite scores, peak vertical ground reaction force, and stabilization indices of kinetic variables after the fatigue protocol (P > .05). Kinetic analysis of repeated tuck jumps after a fatigue protocol identified an altered jumping strategy, which was not identifiable via visual 2-dimensional assessment. However, based on kinetic measures, fatigue induces a stiffer jumping strategy, and practitioners should consider assessing load attenuation strategies that may not be visually evident when evaluating ACL-injury risk factors in athletes who are fatigued.

Educational Model and Prevention on Prediabetes: A Systematic Review.

Prediabetes is a reversible condition before the onset of Type 2 Diabetes Mellitus. Untreated condition of prediabetes will develop into diabetes and its complications. The prevalence of prediabetes has been emerging worldwide and has a considerable socioeconomic impact. The current study reviews the roles of early detection, educational models, life modification, and prophylaxis of individuals with prediabetes in preventing the progression of prediabetes into Type 2 Diabetes Mellitus and complications in the future. This study included published articles from several electronic databases. The obtained articles were limited to March 2023. Articles that were not open access and not in Indonesian or English were excluded. The protocol for this study used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. Of 39627 articles, 39601 were excluded due to duplication and did not meet the eligibility criteria. At the final, there were 26 articles that were eligible for systematic review. Prevention of the development of prediabetes into diabetes is essential. A comprehensive understanding and training on intensive lifestyle modification protocols from local and national experts in diabetes prevention through digital-based education models and linguistically and culturally approach can be considered. Intensive lifestyle modification and pharmacological approaches may improve the outcome. Regular monitoring of glycemic control is also important for early diagnosis of diabetes, especially in patients with special conditions.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer

ObjectiveTo report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. MethodsEligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control. ResultsIn the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2–4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). ConclusionSLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging.Study registration:NCT02494063 (ClinicalTrials.gov).

Treating Benzodiazepine Withdrawal in a Bridge Clinic.

Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed benzodiazepine use, rapid inpatient tapers are typically the only option to treat benzodiazepine withdrawal. Substance use disorder bridge clinics can provide the high-touch care needed to manage outpatient benzodiazepine tapers in patients at high risk due to other substance use disorders. Describe the implementation and short-term outcomes of an outpatient benzodiazepine taper protocol to treat benzodiazepine withdrawal in a substance use disorder bridge clinic. The clinical team developed a 4- to 6-week intensive outpatient taper protocol using diazepam. Patients with benzodiazepine use disorder were eligible if they had benzodiazepine withdrawal, lacked a prescriber, wanted to stop benzodiazepines completely, and agreed to daily visits. For patients who initiated a taper between April 2021 and December 2022, we evaluated the proportion of patients who completed a taper (i.e., tapered to a last prescribed dose of diazepam 10 mg/d or less); likelihood of remaining on the taper over time; and seizure, overdose, or death documented at the study institution during or within 1 month of taper completion or discontinuation. Other secondary outcomes included HIV testing and prevention, hepatitis C testing, and referrals to recovery coaching or psychiatry. Fifty-four patients initiated a total of 60 benzodiazepine tapers. The population was mostly male (61%) and non-Hispanic White (85%). Nearly all patients had opioid use disorder (96%), and most (80%) were taking methadone or buprenorphine for opioid use disorder before starting the taper. Patients reported using multiple substances in addition to benzodiazepines, most commonly fentanyl (75%), followed by cocaine (41%) and methamphetamine (21%). Fourteen patients (23%) completed a taper with a median duration of 34 days (IQR 27.8-43.5). Most tapers were stopped when the patient was lost to follow-up (57%), or the team recommended inpatient care (18%). Two patients had a seizure, and 4 had a presumed opioid-involved overdose during or within 1 month after the last taper visit, all individuals who did not complete a taper. No deaths occurred during or within 1 month of taper completion or discontinuation. Challenges included frequent loss to follow-up in the setting of other unstable substance use. Patients received other high-priority care during the taper including HIV testing (32%), PrEP initiation (6.7%), hepatitis C testing (30%), and referrals to recovery coaches (18%) and psychiatry (6.7%). Managing benzodiazepine withdrawal with a 4- to 6-week intensive outpatient taper in patients with benzodiazepine and opioid use disorders is challenging. More work is needed to refine patient selection, balance safety risks with feasibility, and study long-term, patient-centered outcomes.

Hybrid SPEAK OUT! protocol improves aerodynamic measurements and PROMs in Parkinson's disease.

SPEAK OUT! has been shown to enhance various aspects of voice such as intensity, prosody, voice quality and perception of voice. However, their impacts on expiration and communication effectiveness have not yet been evaluated. This study aimed to evaluate the effectiveness of the Hybrid SPEAK OUT! method on aerodynamic measurements and patient-reported outcome measures (PROMs) in individuals with Parkinson's disease (PD). This study included 157 participants with PD who underwent an intensive 8-week multidisciplinary treatment program. The Hybrid SPEAK OUT! method consisted of three sessions per week, including two group sessions and one individual treatment session. Voice-related aerodynamic measures included maximum phonation time (MPT), vocal cord function using the S/Z ratio, and expiratory flow measures including peakexpiratoryflow (PEF) and peak cough flow (PCF). Two PROMs were included: the Hebrew version of the voice handicap index-10 and communication effectiveness questionnaire. The results of 111 participants were analysed. MPT duration increased, PEF and PCF increased, and better scores were found in PROMs. These findings would appear to support the effectiveness of the Hybrid SPEAK OUT! methods improving function, activity and participation in individuals with PD. However, further research is needed. What is already known on the subject Prior research has demonstrated the effectiveness of behavioral therapies, including the SPEAK OUT! program, in managing speech symptoms in individuals with Parkinson's disease (PD). These therapies have shown improvements in voice intensity, fundamental frequency, voice quality, and voice perception. However, the impact on aerodynamic measures, expiratory flow, and patient-reported outcome measures has not been extensively studied. What this paper adds to existing knowledge This study adds to the existing knowledge by demonstrating that a Hybrid SPEAK OUT! approach, can lead to improvements in aerodynamic measures, including maximum phonation time (MPT), expiratory and cough peak flow. In terms of motor learning, we found that two non-speech exhalation-related tasks that were not directly trained improved following the intensive speech training protocol. Furthermore, it shows positive changes in patient-reported outcome measures, with reduced voice-related disability and improved communication efficiency. What are the potential or actual clinical implications of this work? The findings of this study have important clinical implications for the management of speech symptoms in individuals with PD. The Hybrid SPEAK OUT! program, which combines group and individual sessions, can effectively improve voice, aerodynamic measurements and patient-reported outcome measures (PROMs), ultimately enhancing the overall quality of life for patients. These findings support the effectiveness of the Hybrid SPEAK OUT! methods for improving function, activity, and participation in individuals with PD.

Spark-Discharge-Activated 3D-Printed Electrochemical Sensors.

3D printing technology is a tremendously powerful technology to fabricate electrochemical sensing devices. However, current conductive filaments are not aimed at electrochemical applications and therefore require intense activation protocols to unleash a suitable electrochemical performance. Current activation methods based on (electro)chemical activation (using strong alkaline solutions and organic solvents and/or electrochemical treatments) or combined approaches are time-consuming and require hazardous chemicals and dedicated operator intervention. Here, pioneering spark-discharge-activated 3D-printed electrodes were developed and characterized, and it was demonstrated that their electrochemical performance was greatly improved by the effective removal of the thermoplastic support polylactic acid (PLA) as well as the formation of sponge-like and low-dimensional carbon nanostructures. This reagent-free approach consists of a direct, fast, and automatized spark discharge between the 3D-electrode and the respective graphite pencil electrode tip using a high-voltage power supply. Activated electrodes were challenged toward the simultaneous voltammetric determination of dopamine (DP) and serotonin (5-HT) in cell culture media. Spark discharge has been demonstrated as a promising approach for conductive filament activation as it is a fast, green (0.94 GREEnness Metric Approach), and automatized procedure that can be integrated into the 3D printing pipeline.

The impact of intensive blood pressure management in the post-thrombolysis setting: a real-world observational study.

Systolic blood pressure (SBP) >180mmHg following stroke thrombolysis has been associated with increased bleeding and poorer outcome. Aiming for the guideline SBP of <180mmHg often leads to SBP overshoot, as treatment is only triggered if this threshold is passed. We tested whether a lower target would result in fewer high SBP protocol violations. This is a single-centre, sequential comparison of two blood pressure protocols. Between 2013 and 2017, the guideline-based post-thrombolysis SBP target of <180mmHg was compared with a new protocol aiming for 140-160mmHg. The primary outcome was rate of patients with SBPs >180mmHg. Secondary outcomes included rates of SBP <120 mmHg, antihypertensive infusion use, symptomatic intracerebral haemorrhage (sICH) and 3-month functional independence (modified Rankin Score [mRS] 0-2). Results were adjusted for age, baseline function and stroke severity using regression analysis. During the 23 months preceding and 18 months following the transition to the new protocol, 68 and 100 patients were thrombolysed respectively. Baseline characteristics were similar between groups. The odds of one or more SBPs >180mmHg trended lower in the intensive group (adjusted odds ratio [aOR] 0.61; 95% confidence interval [CI] 0.32-1.17; p=0.14). There was a higher rate of SBPs <120mmHg (aOR 3.09; 95% CI 1.49-6.40; p=0.002) in the intensive BP protocol group. sICH rate and 3-month mRS 0-2 were similar between groups. The more intensive post-thrombolysis BP protocol was associated with a significant increase in sub-optimally low BP events, with a non-significant trend toward fewer high BP protocol violations and unaffected patient outcomes.

Structures and Strategies for Retaining an International Pediatric Cohort from Birth: Lessons from The Environmental Determinants of Diabetes in the Young (TEDDY) Study.

Retention of study participants in observational studies is essential to maintaining the representativeness of the population, minimizing selection bias, and assuring sufficient statistical power. The aim of this report is to describe the structures and strategies used to retain participants in The Environmental Determinants of Diabetes in the Young (TEDDY) Study, an observational study of children at increased genetic risk for type 1 diabetes followed in an intense protocol with frequent clinic visits from birth until age 15. A systematic review of methodologies used to retain research subjects identified four domains: barrier reduction strategies; community building strategies; follow-up/reminder strategies; and tracing strategies. Independent reviewers categorized the retention strategies implemented by the TEDDY Study into each of these domains. Strategies not fitting into any of these categories were placed into a fifth category unique to TEDDY. TEDDY identified over one hundred retention strategies used during the 15 years of follow-up; most could be categorized in these domains. Those unique to TEDDY included (1) study organization and structures to support retention; (2) efforts to meet the changing developmental needs of the TEDDY population, (3) implementation of efforts to address protocol challenges in real-time; and (4) employment of a re-engagement protocol for those who had dropped out of the study. Pediatric cohort studies should include strategies, structures, and resources addressing retention at the study's initiation. It is recommended that child and parent engagement in addition to the developmental needs of the child be an integrated focus of all strategies. Putting mechanisms in place to address protocol and retention challenges in real time would facilitate effectively addressing challenges as they arise. ClinicalTrials.gov Identifier: NCT00279318.