Supporting parents' emotional and mental health in the antenatal consultation.

Supporting parents' emotional and mental health is crucial during antenatal consultations, in which expectant parents often receive serious news about their infant and sometimes face complex antenatal or postnatal decision-making. Being considerate of the circumstances to mitigate barriers and stressors, utilizing clear and sensitive language, and personalizing counseling and decision-making to support parents' pluralistic values are strategies that individual neonatologists can use to promote parents' mental wellness in these encounters. Partnership with clinicians of other disciplines and professions in antenatal consultations can help in providing additional medical information and parent support; however, care must be coordinated within the team to ensure that confusing or conflicting counseling is avoided. In addition to improving communication skills for these encounters as individuals and teams, opportunities also exist to enhance support of parents' mental health at the institutional and national level.

The CAMPUS Study: A Systems Approach to Alcohol-Involved Sexual Violence on College Campuses.

OBJECTIVE: Developing a better mechanistic and multilevel understanding of sexual violence on college campuses can help us evaluate and implement existing interventions, as well as develop new ones. We brought together scientists, practitioners, and college students to collaboratively characterize the systems surrounding alcohol-involved sexual violence on college campuses. Using collaborative model-building, they created models that highlight interconnected and multilevel influences and consequences of sexual violence. METHOD: Collaborative model-building activities involved two collaborator groups (twelve students and eight practitioners) and a core modeling team (seven scientists). Each collaborator group met for four two-hour sessions to develop systems models of alcohol use and sexual violence on college campuses. The core modeling team facilitated each session and worked between sessions to ensure the successful development of the model. Specific activities included identifying and prioritizing the causes and consequences of alcohol-involved sexual violence, characterizing the causal relationships between these factors, and developing and modifying causal loop diagrams to illustrate these relationships. RESULTS: Both students and practitioners identified key causes and consequences, including both individual-level (e.g., drinking to intoxication) and campus-level (e.g., institutional support for survivors) constructs. Both groups identified the causal relationships between these variables and identified salient, modifiable mechanisms for reducing alcohol-involved sexual violence. CONCLUSIONS: The collaborative model-building process successfully included diverse collaborator voices, integrating influential factors across multiple social-ecological levels. This iterative and capability-building approach can bridge intensive modeling efforts with the implementation and development of more effective sexual violence interventions.

Musculoskeletal Injuries, Exercise Behaviors, and Reproductive Health Are Related to Physical Fitness of Female First-Responders and Health Care Providers.

Introduction: Musculoskeletal injuries (MSKi) are the most common injury type experienced by first-responders and health care providers (HCPs), making them a significant threat to physical and mental well-being. Female reproductive health and injury history has been related to physical fitness in female members of the Canadian Armed Forces. This relationship has not been explored in Canadian protective services personnel (first-responders) or HCPs. Methods: Fifty-seven females employed as firefighters, paramedics, law enforcements, or HCPs completed a physical fitness protocol to assess the following: (1) muscular power (standing long jump and medicine ball throw), (2) muscular strength (4 repetition maximum (4RM) back squats and bench press), (3) muscular endurance (Biering-Sorenson test, single-leg wall sit, and push-ups), (4) flexibility (sit-and-reach), and (5) aerobic capacity (graded treadmill VO2max test). Spearman rho correlation analyses were applied to descriptive analysis, independent-samples t-test, one-way ANCOVA (adjusted by age), and chi-square test. Spearman rho correlation analyses were used to compare physical fitness results for female reproductive health history (e.g., parity status), previous MSKi, and physical activity behaviors (e.g., sports participation). A p value of <0.05 is considered significant. Results: History of childbirth, body composition, and exercise behaviors were related to physical fitness (i.e., standing long jump, Biering-Sorenson test, bench press, and back squat) in law enforcement, firefighting, paramedicine, and health care personnel. Conclusions: Physical training programs aimed at supporting parous first-responders or HCPs should emphasize lower body power, lower body strength, and upper body strength.

Are physical fitness, a history of childbirth and injury history related to knee valgus in female Canadian Armed Forces members during a bodyweight overhead squat movement?

OBJECTIVES: A history of childbirth is associated with musculoskeletal injury (MSKi) in female members of the Canadian Armed Forces (CAF). While previous injury and pregnancy impact knee kinematics, it is unclear if a history of childbirth is associated with medial knee displacement (MKD) in an overhead squat movement screen. The aim of this study is to examine the relationship between MKD and (1) MSKi and (2) parity status in female CAF members. METHODS: 24 nulliparous and 21 parous female participants employed by the CAF completed a comprehensive physical fitness assessment of muscular flexibility, power, strength, endurance, aerobic capacity and a bodyweight overhead squat movement screen (recorded using two-dimensional video, and hip-knee-ankle angle measured using Kinovea software). Interactions between MKD, parity status and MSKi history were assessed by one-way analysis of variance and two-way analysis of covariance (ANCOVA) (adjusted for age). RESULTS: An interaction between parity status and acute injury of the lower extremity was observed (F=4.379, p=0.043, η2 =0.099) in MKD of the right knee. The two-way ANCOVA examining acute injury of the lumbopelvic hip complex (lower back, pelvis, hip) yielded an interaction between acute injury to the lumbopelvic hip complex and parity status (F=4.601, p=0.038, η2=0.103) in MKD asymmetry. DISCUSSION: Parous participants with acute injury to the lower extremity had larger MKD than parous without this injury type. Parous participants without acute injury to the lumbopelvic hip complex had greater MKD asymmetry than nulliparous without this injury type. Our findings suggest that researchers and clinicians should consider parity status in conjunction with MSKi history when assessing knee kinematics in female military members.

Periocular fibrosarcoma with lipogranulomatous conjunctivitis in a cat.

A 9-year-old, female spayed domestic short-haired cat was presented with a 4-year history of bilateral lipogranulomatous conjunctivitis (LGC), which was confirmed via histopathology. Thirteen months following the initial biopsy, the cat was presented with a rapidly progressive mass lesion of the palpebral conjunctiva of the right eye. A surgical debulking, followed 1 month later by exenteration after marked regrowth of the mass confirmed fibrosarcoma. This case report is the first to describe a cat with chronic bilateral LGC that later developed a unilateral fibrosarcoma within the eyelid tissue of the right eye. Fibrosarcoma should be considered a differential in any cat with chronic LGC that develops a rapidly progressive mass in the eyelid.

The effect of non-immersive virtual reality radiographic positioning simulation on first-year radiography students' image evaluation performance.

INTRODUCTION: Optimal radiographic image quality is critical because it affects the accuracy of the reporter's interpretation. Radiographers have an ethical obligation to obtain quality diagnostic images while protecting patients from unnecessary radiation, including minimizing rejected and repeated images. Repeated imaging due to positioning errors have increased in recent years. METHODS: This study evaluated the effectiveness of non-immersive virtual reality (VR) simulation on first-year students' evaluation of positioning errors on resultant knee and lumbar spine images. Crossover intervention design was used to deliver radiographic image evaluation instruction through traditional lecture and guided simulation using non-immersive VR to 33 first-year radiography students at a single academic institution located across four geographic program locations. Pre- and post-test knowledge assessments examined participants' ability to recognize positioning errors on multiple-choice and essay questions. RESULTS: Raw mean scores increased on multiple choice questions across the entire cohort for the knee (M = 0.82, SD = 3.38) and lumbar spine (M = 2.91, SD = 3.69) but there was no significant difference in performance by instructional method (p = 0.60). Essay questions reported very minimal to no raw mean score increases for the knee (M = 0.27, SD = 2.78) and lumbar spine (M = 0.00, SD = 2.55), with no significant difference in performance by instructional method (p = 0.72). CONCLUSION: Guided simulation instruction was shown to be as effective as traditional lecture. Results also suggest that novice learners better recognize image evaluation errors and corrections from a list of options but have not yet achieved the level of competence needed to independently evaluate radiographic images for diagnostic criteria. IMPLICATIONS FOR PRACTICE: Non-immersive VR simulation is an effective tool for image evaluation instruction. VR increases access to authentic image evaluation practice by providing a simulated resultant image based off the students' applied positioning skills.

A review of the mesotheliogenic potency of cleavage fragments found in talc.

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

Not Dandy Walker variant: a review of prominent retrocerebellar CSF space in children.

The prominent retrocerebellar cerebrospinal fluid (CSF) space can be frequently encountered on paediatric neuroimaging studies. In cases involving abnormal vermian development where imaging does not align with the established criteria of Dandy-Walker malformation (DWM), the term "Dandy-Walker variant or continuum" has been historically employed to describe the aberrant posterior fossa development. Instead, the emphasis is on a more elaborate description of the findings in the posterior fossa. Moreover, combining the findings in the supratentorial brain can occasionally predict certain neurogenetic disorders that mimic Dandy-Walker phenotype. The present review demonstrates and differentiates the imaging features of various entities that result in an enlarged retrocerebellar CSF space, such as inferior vermian hypoplasia (IVH) and several neurogenetic conditions.

Opioid Prescribing Patterns Following Lateral Skull Base Spontaneous Cerebrospinal Fluid Leak Repair.

OBJECTIVE: To characterize the opioid prescribing patterns for and requirements of patients undergoing repair of spontaneous cerebrospinal fluid (sCSF) leaks of the lateral skull base. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adults with lateral skull base sCSF leaks who underwent repairs between September 1, 2014, and December 31, 2020. MAIN OUTCOME MEASURE: Mean morphine milligram equivalents (MMEs) of opioids dispensed to inpatients and prescribed at discharge, additional pain control medications dispensed, and outpatient additional opioid requests were compared between groups. RESULTS: Of 78 patients included, 46 (59%) underwent repair via a transmastoid (TM), 6 (7.7%) via a middle cranial fossa (MCF), and 26 (33.3%) via a combined TM-MCF approach. Inpatients received a mean of 21.3, 31.4, and 37.6 MMEs per day during admission for the TM, MCF, and combined TM-MCF approaches, respectively ( p = 0.019, ηp 2 = 0.101). Upon discharge, nearly all patients (n = 74, 94.9%) received opioids; 27.3, 32.5, and 37.6 MMEs per day were prescribed after the TM, MCF, and TM-MCF approaches, respectively ( p = 0.015, ηp 2 = 0.093). Five (6.4%) patients requested additional outpatient pain medication, after which three were prescribed 36.7 MMEs per day. Patients with idiopathic intracranial hypertension required significantly more inpatient MMEs than those without (41.5 versus 25.2, p = 0.02, d = 0.689), as did patients with a history of headaches (39.6 versus 23.6, p = 0.042, d = 0.684). CONCLUSIONS: Patients undergoing sCSF leak repair via the MCF or TM-MCF approaches are prescribed more opioids postoperatively than patients undergoing the TM approach. Patients with a history of headaches or idiopathic intracranial hypertension might require more opioids postoperatively.

Assessment of worst-case potential airborne asbestos exposure associated with the use of cosmetic talc: application of an exponential decay model.

Talc is used in cosmetic products to confer desirable properties, such as moisture absorption and smooth texture, to the finished products. Concerns have been raised about the potential presence of asbestos in products containing cosmetic talc. Reconstruction of potential asbestos exposure from the use of cosmetic talc products (assuming a trace level of asbestos) requires consideration of consumer use patterns. Although application generally only lasts seconds, exposure theoretically may continue if the consumer remains in the immediate vicinity. Most published exposure measurements have not adequately characterized the potential for continued exposure. In this analysis, estimates and measurements of airborne asbestos fiber concentrations associated with cosmetic talc use from 10 published studies were used as inputs to an exponential decay model to estimate "worst-case" exposure during and following application. The resulting geometric mean 30-min time-weighted average (TWA) concentrations were 0.006 f/cc for both puff and shaker application, for diapering, 0.0001 f/cc (adult applying baby powder) and 0.0002 f/cc (infant), and for makeup application, 0.0005 f/cc. Application of an exponential decay model to measured or estimated asbestos concentrations associated with the use of cosmetic talc products yields a conservative means to comprehensively reconstruct such exposures. Moreover, our results support that, if a cosmetic talc powder product contained a trace level of asbestos fibers, the "worst-case" airborne asbestos exposure associated with its application is low.

Non-Positive Experiences Encountered by Pupils During Participation in a Mindfulness-Informed School-Based Intervention.

Mindfulness-informed school-based mental health curricula show much promise in cultivating a positive school climate which supports the well-being and mental health of pupils and staff. However, non-positive pupil outcomes and experiences of school-based mental health interventions are often under-recognised and under-reported. This study sought to capture non-positive pupil experiences of a popular mindfulness-informed curriculum. Some pupils across all schools in the study described non-positive experiences, including having troubling thoughts and emotions, and not finding the programme effective. Contexts surrounding these experiences are explored and linked to existing literature, and subsequent recommendations for improvements are made, including the importance of having clear programme structure, definitions and aims, acknowledging and accommodating fidelity issues as best as possible, and better highlighting the potential for non-positive experiences and how they may be reduced.

Secondary School Athletic Trainers' Clinical Management Decisions of Low Socioeconomic Status Patients.

CONTEXT: Evidence suggests that negative social determinants of health (SDOH) and lower socioeconomic status (SES) contribute to health care disparities. Due to their accessibility in the high school setting, secondary school athletic trainers (SSATs) may encounter patients that are historically underserved in health care such as low SES patients. However, there is a significant gap in knowledge regarding how SES and SDOH may influence SSATs' clinical management decisions. OBJECTIVE: The purpose of this study was to describe SSATs' perceptions of how patient SDOH and SES influence clinical management decisions and to identify barriers to athletic healthcare. DESIGN: Cross-sectional study. SETTING: Online survey. PARTICIPANTS: NATA SSATs (6.7% response rate). MAIN OUTCOME MEASURE(S): SSATs were asked about their perceptions of patient SES and the SDOH (CVI = 0.83 for relevancy). Questions were ranked on a 4-point Liker scale on level of relevance and agreement. Data were summarized by means and standard deviations (SD), frequencies and proportions (%), and median scores. RESULTS: A total of 380 SSATs participated (years of experience mean=14.9±11.7 years). When providing care, most (71.3%) SSATs believed that their patient's health/health care access SDOH to be the most relevant of the 5 SDOH whereas the other 4 SDOH were less than 60% relevant. Most SSATs agreed/strongly agreed that patient SES impacts referral (67.4%) and the reliance on conservative treatment before referral (71.2%). SSATs identified patient/guardian compliance (70.2%) and type of health insurance (61.5%) as barriers to providing care to low SES patients. CONCLUSIONS: SSATs perceived health/health care access as the most relevant SDOH when providing care to low SES patients. When SSATs further considered the SES of patients, they identified all SDOHs as barriers to providing health care they were ill equipped to navigate as they delivered care and engaged in patient referral.

Reduced-order modeling and analysis of dynamic cerebral autoregulation via diffusion maps.

Objective.A data-driven technique for parsimonious modeling and analysis of dynamic cerebral autoregulation (DCA) is developed based on the concept of diffusion maps. Specifically, first, a state-space description of DCA dynamics is considered based on arterial blood pressure, cerebral blood flow velocity, and their time derivatives. Next, an eigenvalue analysis of the Markov matrix of a random walk on a graph over the dataset domain yields a low-dimensional representation of the intrinsic dynamics. Further dimension reduction is made possible by accounting only for the two most significant eigenvalues. The value of their ratio indicates whether the underlying system is governed by active or hypoactive dynamics, indicating healthy or impaired DCA function, respectively. We assessed the reliability of the technique by considering healthy individuals and patients with unilateral internal carotid artery (ICA) stenosis or occlusion. We computed the sensitivity of the technique to detect the presumed side-to-side difference in the DCA function of the second group (assuming hypoactive dynamics on the occluded or stenotic side), using McNemar's chi square test. The results were compared with transfer function analysis (TFA). The performance of the two methods was also compared under the assumption of missing data.Main results.Both diffusion maps and TFA suggested a physiological side-to-side difference in the DCA of ICA stenosis or occlusion patients with a sensitivity of 81% and 71%, respectively. Further, both two methods suggested the difference between the occluded or stenotic side and any two sides of the healthy group. However, the diffusion maps captured additional difference between the unoccluded side and the healthy group, that TFA did not. Furthermore, compared to TFA, diffusion maps exhibited superior performance when subject to missing data.Significance.The eigenvalues ratio derived using the diffusion maps technique can be potentially used as a reliable and robust biomarker for assessing how active the intrinsic dynamics of the autoregulation is and for indicating healthy versus impaired DCA function.

Validation of a shortened MR imaging protocol for pediatric spinal pathology.

OBJECTIVE: Conventional pediatric spine MRI protocols have multiple sequences resulting in long acquisition times. Sedation is consequently required. This study evaluates the diagnostic capability of a limited MRI spine protocol for selected common pediatric indications. METHODS: Spine MRIs at CHEO between 2017 and 2020 were reviewed across pediatric patients younger than four years old. Two blinded neuroradiologists reviewed limited scan sequences, and results were independently compared to previously reported findings from the complete imaging series. T2 sagittal sequences from the craniocervical junction to sacrum and T1 axial sequence of the lumbar spine constitute the short protocol, with the outcomes of interest being cerebellar ectopia, syrinx, level of conus, filum < 2 mm, fatty filum, and spinal dysraphism. RESULTS: A total of 105 studies were evaluated in 54 male and 51 female patients (mean age 19.2 months). The average combined scan time of the limited sequences was 15 min compared to 35 min for conventional protocols (delta = 20 min). The average percent agreement between full and limited sequences was > 95% in all but identifying a filum < 2 mm, where the percent agreement was 87%. Using limited MR sequences had high sensitivity (> 0.91) and specificity (> 0.99) for the detection of cerebellar ectopia, syrinx, fatty filum, and spinal dysraphism. CONCLUSION: This study demonstrates that selected spinal imaging sequences allow for consistent and accurate diagnosis of specific clinical conditions. A limited spine imaging protocol has potential as a screening test to reduce the need for full-sequence MRI scans. Further work is needed to determine utility of selected imaging for other clinical indications.

Point-of-care ultrasound use in emergencies: what every anaesthetist should know.

Point-of-care ultrasound has been embraced by anaesthetists as an invaluable tool for rapid diagnosis of haemodynamic instability, to ensure procedural safety and monitor response to treatments. Increasingly available, affordable and portable, with emerging evidence of improved patient outcomes, point-of-care ultrasound has become a valuable tool in the emergency setting. This state-of-the-art review describes the feasibility of point-of-care ultrasound practice, training and maintenance of competence. It also describes the many uses of point-of-care ultrasound for the anaesthetist and describes the most salient point-of-care ultrasound views for anaesthetic emergencies including: undifferentiated shock; hypoxemia; and trauma. Procedural safety is also discussed in addition to relevant important governance aspects. Cardiac function should be assessed using the parasternal long axis, parasternal short basal/mid-papillary/apical, apical four chamber and subcostal four chamber views, and should include a visual estimation of global left ventricular ejection fraction. Other cardiovascular conditions that can be identified using point-of-care ultrasound include: pericardial effusion; cardiac tamponade; and pulmonary embolism. Pulmonary emergency conditions that can be diagnosed using point-of-care ultrasound include pneumothorax; pleural effusion; and interstitial syndrome. The extended focused assessment with sonography for trauma examination may of value in patients who are hypotensive in order to identify intra-abdominal haemorrhage, pneumothoraces and haemothoraces.

Impact of 10-Day Fulbright Specialist Program and Project Pink Blue Education Sessions on Medical Oncology Knowledge Among Physicians Who Treat Cancer in Nigeria.

Despite an estimated population of over 201 million and over 115,950 yearly diagnosed new cases of cancer, Nigeria does not have dedicated medical oncologists. Most oncology care is delivered through surgical and clinical oncologists, who are trained in both radiation and medical oncology and they number fewer than 50 in the country. With a limited number of oncology professionals, cancer patients in Nigeria experience poor health outcomes, with an estimated cancer mortality rate of 75,000 deaths per year. Participants from 15 Nigerian states were selected to attend the medical oncology training. Through the support of Fulbright Specialist Program and Project PINK BLUE, two of the authors delivered 10 days of lectures based on ASCO, ESMO, and NCCN guidelines. Mean scores of both the pre- and post-course tests as well as a 1-year follow-up test were compared using GraphPad Prism 7.0a by paired t-tests. Forty-four clinical oncologists were selected for participation. Twenty-five (57%) completed the pre- and post-course tests. Of the 25 that completed both tests, percentage of correct answers increased from 45 to 59% (2-sided p-value < 0.0001). Improvements were seen in attending doctors 45 to 59% (p = 0.0046) and resident doctors 45 to 59% (0.0007). Eleven doctors responded to the 1-year follow-up test. Although not statistically significant, a numerical pattern for the benefits was maintained 1 year after the program (45% pre-course versus 52% post-course correct answers, Fisher's exact, p = 0.4185). In the short term, the training improved medical oncology knowledge in Nigeria, regardless of the participant's carrier stage. Long-term benefits were not sustained in a small sample of participants, and continuing education strategies are necessary. Similar models may be employed across Africa.

Anaesthesia for vascular emergencies - a state of the art review.

In this state-of-the-art review, we discuss the presenting symptoms and management strategies for vascular emergencies. Although vascular emergencies are best treated at a vascular surgical centre, patients may present to any emergency department and may require both immediate management and safe transport to a vascular centre. We describe the surgical and anaesthetic considerations for management of aortic dissection, aortic rupture, carotid endarterectomy, acute limb ischaemia and mesenteric ischaemia. Important issues to consider in aortic dissection are extent of the dissection and surgical need for bypasses in addition to endovascular repair. From an anaesthetist's perspective, aortic dissection requires infrastructure for massive transfusion, smooth management should an endovascular procedure require conversion to an open procedure, haemodynamic manipulation during stent deployment and prevention of spinal cord ischaemia. Principles in management of aortic rupture, whether open or endovascular treatment is chosen, include immediate transfer to a vascular care centre; minimising haemodynamic changes to reduce aortic shear stress; permissive hypotension in the pre-operative period; and initiation of massive transfusion protocol. Carotid endarterectomy for carotid stenosis is managed with general or regional techniques, and anaesthetists must be prepared to manage haemodynamic, neurological and airway issues peri-operatively. Acute limb ischaemia is a result of embolism, thrombosis, dissection or trauma, and may be treated with open repair or embolectomy, under either general or local anaesthesia. Due to hypercoagulability, there may be higher numbers of acutely ischaemic limbs among patients with COVID-19, which is important to consider in the current pandemic. Mesenteric ischaemia is a rare vascular emergency, but it is challenging to diagnose and associated with high morbidity and mortality. Several peri-operative issues are common to all vascular emergencies: acute renal injury; management of transfusion; need for heparinisation and reversal; and challenging postoperative care. Finally, the important development of endovascular techniques for repair in many vascular emergencies has improved care, and the availability of transoesophageal echocardiography has improved monitoring as well as aids in surgical placement of endovascular grafts and for post-procedural evaluation.

Changing Parental Knowledge and Treatment Acceptance for ADHD: A Pilot Study.

This pilot study assessed the feasibility and potential effectiveness of a single-session workshop in modifying parental beliefs/knowledge about attention-deficit/hyperactivity disorder (ADHD) in children and impact on treatment acceptance/utilization. Concerns raised by school professionals about lack of treatment follow-through after ADHD diagnosis and parental misinformation about medication usage catalyzed this project. A single-group pre-post quasi-experimental design was used. Sixty-eight parents completed ADHD knowledge/belief scales and stress inventories, and pre-ADHD and post-ADHD information workshop. Follow-up calls were made after the workshop to assess treatment utilization. Parents/caregivers experienced significant knowledge and belief changes regarding medication efficacy, willingness to accept physician treatment recommendations, and rejection of non-empirically based treatments. Follow-up data showed that 41% of contacted participants met with physicians to discuss medication utilization and behavioral treatments. Brief, one-session psycho-educational workshops were feasible and impacted parental beliefs and behaviors regarding scientifically supported interventions for ADHD.

American Speech-Language-Hearing Association Clinical Practice Guideline: Cognitive Rehabilitation for the Management of Cognitive Dysfunction Associated With Acquired Brain Injury.

BACKGROUND: Cognitive-communication impairments following acquired brain injury (ABI) can have devastating effects on a person's ability to participate in community, social, vocational, and academic preinjury roles and responsibilities. Guidelines for evidence-based practices are needed to assist speech-language pathologists (SLPs) and other rehabilitation specialists in the delivery of cognitive rehabilitation for the adult population. PURPOSE: The American Speech-Language-Hearing Association, in conjunction with a multidisciplinary panel of subject matter experts, developed this guideline to identify best practice recommendations for the delivery of cognitive rehabilitation to adults with cognitive dysfunction associated with ABI. METHOD: A multidisciplinary panel identified 19 critical questions to be addressed in the guideline. Literature published between 1980 and 2020 was identified based on a set of a priori inclusion/exclusion criteria, and main findings were pooled and organized into summary of findings tables. Following the principles of the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision Framework, the panel drafted recommendations, when appropriate, based on the findings, overall quality of the evidence, balance of benefits and harms, patient preferences, resource implications, and the feasibility and acceptability of cognitive rehabilitation. RECOMMENDATIONS: This guideline includes one overarching evidence-based recommendation that addresses the management of cognitive dysfunction following ABI and 11 subsequent recommendations focusing on cognitive rehabilitation treatment approaches, methods, and manner of delivery. In addition, this guideline includes an overarching consensus-based recommendation and seven additional consensus recommendations highlighting the role of the SLP in the screening, assessment, and treatment of adults with cognitive dysfunction associated with ABI. Future research considerations are also discussed.

A Pt(IV)-conjugated brain penetrant macrocyclic peptide shows pre-clinical efficacy in glioblastoma.

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor, with a median survival of approximately 15 months. Treatment is limited by the blood-brain barrier (BBB) which restricts the passage of most drugs to the brain. We previously reported the design and synthesis of a BBB-penetrant macrocyclic cell-penetrating peptide conjugate (M13) covalently linked at the axial position of a Pt(IV) cisplatin prodrug. Here we show the Pt(IV)-M13 conjugate releases active cisplatin upon intracellular reduction and effects potent in vitro GBM cell killing. Pt(IV)-M13 significantly increased platinum uptake in an in vitro BBB spheroid model and intravenous administration of Pt(IV)-M13 in GBM tumor-bearing mice led to higher platinum levels in brain tissue and intratumorally compared with cisplatin. Pt(IV)-M13 administration was tolerated in naïve nude mice at higher dosage regimes than cisplatin and significantly extended survival above controls in a murine GBM xenograft model (median survival 33 days for Pt(IV)-M13 vs 24 days for Pt(IV) prodrug, 22.5 days for cisplatin and 22 days for control). Increased numbers of γH2AX nuclear foci, biomarkers of DNA damage, were observed in tumors of Pt(IV)-M13-treated mice, consistent with elevated platinum levels. The present work provides the first demonstration that systemic injection of a Pt(IV) complex conjugated to a brain-penetrant macrocyclic peptide can lead to increased platinum levels in the brain and extend survival in mouse GBM models, supporting further development of this approach and the utility of brain-penetrating macrocyclic peptide conjugates for delivering non-BBB penetrant drugs to the central nervous system.