The Changing Prevalence of Pressure Injury among Ontarians with SCI/D at Rehabilitation Admission: Opportunities for Improvement.

BACKGROUND: Despite preventability, 20-50% of patients with acute spinal cord injury/disease (SCI/D) develop hospital-acquired pressure injuries (PIs). The Spinal Cord Injury Implementation and Evaluation Quality Care Consortium (SCI IEQCC) aimed to mitigate PI risk through patient-reported daily skin checks alongside usual care. METHODS: This quality improvement initiative utilized an interrupted time series design, encompassing adults ≥ 18 years admitted for inpatient rehabilitation across five Ontario sites from 2020 to 2023. Patient demographics, etiology, and impairment data were obtained from a national registry, while participating sites gathered data on PI onset, location, and severity. Run charts depicted temporal trends, and statistical analyses, including chi-square and logistic regression, compared patients with and without PIs. RESULTS: Data from 1767 discharged SCI/D patients revealed that 26% had ≥1 PI, with 59% being prevalent and 41% incident. Most severe PIs (stages III and IV and unstageable) were acquired prior to admission. Process indicator fidelity was reasonable at 68%. Patients with PIs experienced longer hospital stays, lower Functional Independence Measure (FIM) changes, and FIM efficiency during rehabilitation. CONCLUSIONS: PI prevalence is increasing, particularly sacral injuries at admission, while incident cases have decreased since 2021 due to regular skin checks. This trend calls for proactive health system interventions to reduce costs and improve patient outcomes.

Mortality and discharge disposition among older adults with moderate to severe traumatic brain injury.

PURPOSE: This study examined the research on older adults with a moderate to severe traumatic brain injury (TBI), with a focus on mortality and discharge disposition. METHOD: Systematic searches were conducted in MEDLINE, CINAHL, EMBASE and PsycINFO for studies up to April 2022 in accordance with PRISMA guidelines. RESULTS: 64 studies, published from 1992 to 2022, met the inclusion criteria. Mortality was higher for older adults ≥60 years old than for their younger counterparts; with a dramatic increase for those ≥80 yr, with rates as high as 93 %. Similar findings were reported regarding mortality in intensive care, surgical mortality, and mortality post-hospital discharge; with an 80 % rate at 1-year post-discharge. Up to 68.4 % of older adults were discharged home; when compared to younger adults, those ≥65 years were less likely to be discharged home (50-51 %), compared to those <64 years (77 %). Older adults were also more likely to be discharged to long-term care (up to 31.6 %), skilled nursing facilities (up to 46.1 %), inpatient rehabilitation (up to 26.9 %), and palliative or hospice care (up to 58 %). CONCLUSION: Given their vulnerability, optimizing outcomes for older adults with moderate-severe TBI across the healthcare continuum is critical.

Musculoskeletal mimics of lumbosacral radiculopathy.

Electrodiagnostic evaluations are commonly requested for patients with suspected radiculopathy. Understanding lower extremity musculoskeletal conditions is essential for electrodiagnostic medicine specialists, as musculoskeletal disorders often mimic or coexist with radiculopathy. This review delineates radicular pain from other types originating from the lumbosacral spine and describes musculoskeletal conditions frequently mimicking radiculopathy, such as those that cause radiating pain and sensorimotor dysfunction. In clinical evaluation, a history of pain radiating along a specific dermatomal territory with associated sensory disturbance suggests radiculopathy. Physical examination findings consistent with radiculopathy include myotomal weakness, depressed or absent muscle stretch reflexes, focal atrophy along a discrete nerve root territory, and potentially positive dural tension maneuvers like the straight leg raise. However, electrodiagnostic medicine specialists must be knowledgeable of musculoskeletal mimics, which may manifest as incomplete radiation within or beyond a dermatomal territory, non-radiating pain, tenderness, and give-way weakness, in the context of a normal neurological examination. A systematic approach to musculoskeletal examination is vital, and this review focuses on high-yield physical examination maneuvers and diagnostic investigations to differentiate between musculoskeletal conditions and radiculopathy. This approach ensures accurate diagnoses, promotes resource stewardship, enhances patient satisfaction, and optimizes care delivery. Musculoskeletal conditions resembling L1 to S4 radiculopathy are reviewed, emphasizing their distinctive features in history, physical examination, and diagnostic investigation. Among the more than 30 musculoskeletal disorders reviewed are hip and knee osteoarthritis, lumbar facet syndrome, myofascial pain syndrome, greater trochanteric pain syndrome, and plantar fasciitis.

Overview of randomized controlled trials of moderate to severe traumatic brain injury: A systematic review.

BACKGROUND: Given the complexity of post-TBI medical, surgical, and rehabilitative care, research is critical to optimize interventions across the continuum of care and improve outcomes for persons with moderate to severe TBI. OBJECTIVE: To characterize randomized controlled trials (RCTs) of moderate to severe traumatic brain injury (TBI) in the literature. METHOD: Systematic searches of MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO for RCTs up to December 2022 inclusive were conducted in accordance with PRISMA guidelines. RESULTS: 662 RCTs of 91,946 participants published from 1978 to 2022 met inclusion criteria. The number of RCTs published annually has increased steadily. The most reported indicator of TBI severity was the Glasgow Coma Scale (545 RCTs, 82.3%). 432 (65.3%) RCTs focused on medical/surgical interventions while 230 (34.7%) addressed rehabilitation. Medical/surgical RCTs had larger sample sizes compared to rehabilitation RCTs. Rehabilitation RCTs accounted for only one third of moderate to severe TBI RCTs and were primarily conducted in the chronic phase post-injury relying on smaller sample sizes. CONCLUSION: Further research in the subacute and chronic phases as well as increasing rehabilitation focused TBI RCTs will be important to optimizing the long-term outcomes and quality of life for persons living with TBI.

Comparing Randomized Controlled Trials of Moderate to Severe Traumatic Brain Injury in Lower to Middle Income Countries Versus High Income Countries.

Outcomes from traumatic brain injury (TBI) including death differ significantly between high-, middle-, and low-income countries. Little is known, however, about differences in TBI research across the globe. The objective of this article was to examine randomized controlled trials (RCTs) of moderate-to-severe TBI in high-income countries (HICs) compared with low- and middle-income countries (LMICs), as defined by the World Bank income per capita cutoff of $13,205 US dollars. A systematic review was conducted for articles published in the English language to December 2022 inclusive using MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria: (1) human participants with a mean age of ≥18 years; (2) ≥50% of the sample had moderate to severe TBI; and (3) the study design was a RCT. Data extracted included author, year, country, sample size, primary focus (medical/surgical management or rehabilitation), injury etiology, time post-injury, and indicator(s) used to define TBI severity. There were 662 RCTs (published 1978-2022) that met inclusion criteria comprising 91,946 participants. There were 48 countries represented: 30 HICs accounting for 451 RCTs (68.1%) and 18 LMICs accounting for 211 RCTs (31.9%). The 62.6% of RCTs from LMICs were conducted in the acute phase post-injury (≤1 month) compared with 42.1% of RCTs from HICs. Of RCTs from LMICs, 92.4% focused on medical/surgical management compared with 52.5% from HICs. Since 2016, more RCTs have been conducted in LMICs than in HICs, indicating the importance of better understanding this pattern of research output.

Fibre-rich diet attenuates chemotherapy-related neuroinflammation in mice.

The gastrointestinal microbiota has received increasing recognition as a key mediator of neurological conditions with neuroinflammatory features, through its production of the bioactive metabolites, short-chain fatty acids (SCFAs). Although neuroinflammation is a hallmark shared by the neuropsychological complications of chemotherapy (including cognitive impairment, fatigue and depression), the use of microbial-based therapeutics has not previously been studied in this setting. Therefore, we aimed to investigate the effect of a high fibre diet known to modulate the microbiota, and its associated metabolome, on neuroinflammation caused by the common chemotherapeutic agent 5-fluorouracil (5-FU). Twenty-four female C57Bl/6 mice were treated with 5-FU (400 mg/kg, intraperitoneal, i.p.) or vehicle control, with or without a high fibre diet (constituting amylose starch; 4.7 % crude fibre content), given one week prior to 5-FU and until study completion (16 days after 5-FU). Faecal pellets were collected longitudinally for 16S rRNA gene sequencing and terminal SCFA concentrations of the caecal contents were quantified using gas chromatography-mass spectrometry (GC-MS). Neuroinflammation was determined by immunofluorescent analysis of astrocyte density (GFAP). The high fibre diet significantly altered gut microbiota composition, increasing the abundance of Bacteroidaceae and Akkermansiaceae (p < 0.0001 and p = 0.0179) whilst increasing the production of propionate (p = 0.0097). In the context of 5-FU, the diet reduced GFAP expression in the CA1 region of the hippocampus (p < 0.0001) as well as the midbrain (p = 0.0216). Astrocyte density negatively correlated with propionate concentrations and the abundance of Bacteroidaceae and Akkermansiaceae, suggesting a relationship between neuroinflammatory and gastrointestinal markers in this model. This study provides the first evidence of the neuroprotective effects of fibre via dietary intake in alleviating the neuroimmune changes seen in response to systemically administered 5-FU, indicating that the microbiota-gut-brain axis is a targetable mediator to reduce the neurotoxic effects of chemotherapy treatment.

Assessment, patient selection, and rehabilitation of nerve transfers.

Peripheral nerve injuries are common and can have a devastating effect on physical, psychological, and socioeconomic wellbeing. Peripheral nerve transfers have become the standard of care for many types of peripheral nerve injury due to their superior outcomes relative to conventional techniques. As the indications for, and use of, nerve transfers expand, the importance of pre-operative assessment and post-operative optimization increases. There are two principal advantages of nerve transfers: (1) their ability to shorten the time to reinnervation of muscles undergoing denervation because of peripheral nerve injury; and (2) their specificity in ensuring proximal motor and sensory axons are directed towards appropriate motor and sensory targets. Compared to conventional nerve grafting, nerve transfers offer opportunities to reinnervate muscles affected by cervical spinal cord injury and to augment natural reinnervation potential for very proximal injuries. This article provides a narrative review of the current scientific knowledge and clinical understanding of nerve transfers including peripheral nerve injury assessment and pre- and post-operative electrodiagnostic testing, adjuvant therapies, and post-operative rehabilitation for optimizing nerve transfer outcomes.

Whey-based diet containing medium chain triglycerides modulates the gut microbiota and protects the intestinal mucosa from chemotherapy while maintaining therapy efficacy.

Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy's cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3/g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P < 0.0001), weight loss (P < 0.05), daily activity (P < 0.02) and maintenance of body composition (P < 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing diversity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury (P = 0.001) and diarrhea (P < 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.

Developing a framework for utilizing adjunct rehabilitation therapies in motor recovery of upper extremity post stroke.

INTRODUCTION: Standardization of first principles has transformed stroke rehabilitation in developed countries and helped guide the appropriate allocation of resources to ensure better outcomes for patients. There have been challenges in incorporating new evidence into stroke rehabilitation practices. The sheer number of RCTs can be daunting to the average clinician, made worse by the lack of a framework for their application. OBJECTIVES: To develop a framework for the introduction of adjunct practices for the motor recovery of the upper extremity post stroke into clinical practice. METHODOLOGY: A literature search following PRISMA guidelines revealed 1,307 RCTs involving rehabilitation interventions for the hemiparetic upper extremity post stroke. RESULTS: Therapies were divided into three categories of therapies: (1) Basic Conventional Therapy Approaches (<15% of interventions), (2) Adjunct Therapies Designed to Enhance Conventional Therapies (>85% of interventions), and (3) Treatment to Manage Complications (~9% of interventions). Adjunct Therapies, despite having a spectacular evidence base, are often not employed clinically. To encourage their clinical use, we have developed a framework that divides adjunct therapies into two categories: (1) Treatments that Stimulate the Brain (i.e. rTMS, mental practice, and virtual reality) and (2) Treatments that Peripherally Facilitate the Hemiparetic Upper Extremity (i.e. robotics, EMG Biofeedback, and Constraint-induced Movement Therapy). CONCLUSION: To allow stroke rehabilitation to continue to improve upper extremity recovery and outcomes, we propose a new intuitive framework that is based on a strong evidence base to guide clinicians and improve stroke rehabilitation.

Compound Kushen injection reduces severity of radiation-induced gastrointestinal mucositis in rats.

Mucositis, or damage/injury to mucous membranes of the alimentary, respiratory, or genitourinary tract, is the major side effect associated with anticancer radiotherapies. Because there is no effective treatment for mucositis at present, this is a particular issue as it limits the dose of therapy in cancer patients and significantly affects their quality of life. Gastrointestinal mucositis (GIM) occurs in patients receiving radiotherapies to treat cancers of the stomach, abdomen, and pelvis. It involves inflammation and ulceration of the gastrointestinal (GI) tract causing diarrhea, nausea and vomiting, abdominal pain, and bloating. However, there is currently no effective treatment for this debilitating condition. In this study, we investigated the potential of a type of traditional Chinese medicine (TCM), compound Kushen injection (CKI), as a treatment for GIM. It has previously been shown that major groups of chemical compounds found in CKI have anti-inflammatory effects and are capable of inhibiting the expression of pro-inflammatory cytokines. Intraperitoneal administration of CKI to Sprague Dawley (SD) rats that concurrently received abdominal irradiation over five fractions resulted in reduced severity of GIM symptoms compared to rats administered a vehicle control. Histological examination of the intestinal tissues revealed significantly less damaged villus epithelium in CKI-administered rats that had reduced numbers of apoptotic cells in the crypts. Furthermore, it was also found that CKI treatment led to decreased levels of inflammatory factors including lower levels of interleukin (IL)-1ß and IL-6 as well as myeloperoxidase (MPO)-producing cells in the intestinal mucosa. Together, our data indicate a novel effect of CKI to reduce the symptoms of radiation-induced GIM by inhibiting inflammation in the mucosa and apoptosis of epithelial cells.

Antibiotic treatment targeting gram negative bacteria prevents neratinib-induced diarrhea in rats.

BACKGROUND: Neratinib is a pan-ErbB tyrosine kinase inhibitor used for extended adjuvant treatment of HER2-positive breast cancer. Diarrhea is the main adverse event associated with neratinib treatment. We aimed here to determine whether antibiotic-induced gut microbial shifts altered development of neratinib-induced diarrhea. METHODS: Female Albino Wistar rats (total n = 44) were given antibiotics (vancomycin, neomycin, or a cocktail of vancomycin, neomycin and ampicillin) in drinking water for four weeks, and then treated daily with neratinib (50 mg/kg) for 28 days. Diarrhea, along with markers of gastrointestinal damage and microbial alterations were measured by histopathology and 16S sequencing, respectively. RESULTS: Rats treated with vancomycin or neomycin had significantly lower levels of diarrhea than rats treated with neratinib alone. In the distal ileum, neratinib was associated with a statistically significant increase in histological damage in all treatment groups expect the antibiotic cocktail. Key features included villous blunting and fusion and some inflammatory infiltrate. Differences in microbial composition at necropsy in vehicle control, neratinib and neratinib + neomycin groups, were characterized by a neratinib-induced increase in gram-negative bacteria that was reversed by neomycin. Neomycin shifted bacterial composition so that Blautia become the dominant genus. CONCLUSIONS: Narrow spectrum antibiotics reduced neratinib-induced diarrhea. This suggests that the microbiome may play a key role in the development and prolongation of diarrhea following neratinib treatment, although further research is required to understand the key bacteria and mechanisms by which they reduce diarrhea, as well as how this may impact presentation of diarrhea in clinical cohorts.

Antibiotic-Induced Gut Microbiota Depletion Accelerates the Recovery of Radiation-Induced Oral Mucositis in Rats.

PURPOSE: Due to its pivotal role in the modulation of immune and inflammatory responses, the gut microbiota has emerged as a key modulator of cancer treatment-induced gastrointestinal mucositis. However, it is not clear yet how it affects radiation therapy-induced oral mucositis (OM). As such, this study aimed to explore the gut microbiota's role in the pathogenesis of radiation-induced OM in rats. METHODS AND MATERIALS: Male Sprague Dawley rats were treated with 20 Gy x-ray radiation (Rx) delivered to the snout, with or without antibiotic-induced microbiota depletion (AIMD). OM severity was assessed, and tongue tissues were collected on day 9 and 15 postradiation for tissue injury and inflammatory markers assessment. RESULTS: AIMD+Rx had a significantly shorter duration of severe OM compared with Rx alone group. Macroscopically, the tongue ulcer-like area was smaller in AIMD+Rx compared with the Rx group. Microscopically, a smaller percentage of the mucosal ulcer was observed in the dorsal tongue of AIMD+Rx compared with the Rx group. AIMD+Rx also had significantly lower levels of interleukin 6, interleukin 1 beta, and toll like receptor 4 in the tongue tissues than the Rx group. CONCLUSIONS: The gut microbiota plays a role in OM pathogenesis, mainly in the recovery phase, through the modulation of proinflammatory pathways. Future microbiota-targeted interventions may improve OM in clinical settings.

Pregnancy After Amputation: A Systematic Review of Pregnancy Experiences for Women With Lower Extremity Amputations.

ABSTRACT: Pregnancy could affect the mobility of women with lower extremity limb loss, deficiency, or amputations. The aim of this systematic review was to characterize the pregnancy-related experiences, including prosthesis, gait aid, and mobility outcomes, of women with lower extremity limb loss, deficiency, or amputations. MEDLINE, CINAHL, and Embase databases were searched for all relevant English-language articles describing pregnancy experiences of women with lower extremity limb loss, deficiency, or amputations. Data extracted were age, amputation level and etiology, obstetrical history, prosthesis and/or gait aid use before, during, and after pregnancy, and pregnancy-related complications. Risk of bias was assessed using applicable CLARITY tools. Data were analyzed with descriptive statistics. Among 399 retrieved studies, 24 met inclusion criteria describing 31 pregnancies in 25 women. All were case series/reports with high risk of bias. All women had acquired lower extremity limb loss, deficiency, or amputations. Sixteen women had hemipelvectomy (64%) and 4 had transfemoral amputations (16%). Three women used a prosthesis, 5 did not, and use was not described for 17 (68%). Prosthesis or gait aid use changed in 2 pregnancies, did not change in 6, and was not specified in 23 (74%). Available cases are likely not representative; additional research is required to characterize the impact of pregnancy on women with lower extremity limb loss, deficiency, or amputations.

Publication Rate of Presentations at a National Physical Medicine and Rehabilitation Scientific Conference From 2009 to 2018.

ABSTRACT: Conferences are important platforms for sharing research, but full-text publication is necessary for broader dissemination and impact. Few studies have examined the abstract-to-publication rate for physical medicine and rehabilitation. This study aimed to determine the abstract-to-publication rate of research abstracts presented from 2009-2018 at the Canadian Association of Physical Medicine and Rehabilitation annual scientific meetings. Using the official book of abstracts from 2009 to 2018, year of conference, abstract title, author names, and the affiliation/level of training of the first author were extracted. Systematic searches of abstract key words, authors' names, and the abstract title were performed using PubMed and Google Scholar to determine whether an abstract proceeded to full-text publication; if so, the date and journal of publication were extracted. Of the 524 total abstracts presented at the Canadian Association of Physical Medicine and Rehabilitation from 2009 to 2018, 187 went on to full-text publication for an abstract-to-publication rate of 35.8%. The mean time to full-text publication was 23.4 ± 8.63 mos. The abstract-to-publication rate was 18.6% for medical students, 28.7% for residents, 41.1% for physical medicine and rehabilitation consultants, and 49.4% for nonphysician presenters. This study highlights that low abstract-to-publication rates for novel research presented at the Canadian Association of Physical Medicine and Rehabilitation disproportionately affects trainees. Further research is needed to identify and remedy barriers to publication.

Postural neurologic deficits after decompressive craniectomy: A case series of sinking skin flap syndrome in traumatic brain injury.

BACKGROUND: Hemicraniectomy to manage raised intracranial pressure following traumatic brain injury (TBI) has improved survival but may increase the incidence of Sinking Skin Flap Syndrome (SSFS). SSFS is a clinical syndrome in which patients with craniectomy develop objective neurologic abnormalities due to the pressure of the atmosphere on the unprotected brain, often presenting with postural headaches and neurologic deficits that localize to the craniectomy site. Previously thought to be a rare complication of craniectomy after TBI, evidence suggests SSFS is under-recognized. OBJECTIVE: To describe the clinical and radiographic features leading to diagnosis and the impact of temporizing and definitive management of SSFS on outcomes in inpatients with moderate/severe TBI. METHODS: Two patients' symptoms, qualitative behaviour observation, physical and cognitive outcome measures, and neuroimaging pre- and post-temporizing measures and cranioplasty are presented. RESULTS: Both patients demonstrated partial improvements with temporizing measures and substantial improvements in functional, cognitive, physical, and rehabilitation outcomes from the cranioplasty and resolution of SSFS. CONCLUSIONS: Rehabilitation care providers are critical to the timely diagnosis and management of SSFS, including the use of temporizing measures and advocacy for definitive treatment with cranioplasty. These cases highlight the diverse clinical presentations and importance of SSFS diagnosis to improve patient outcomes.

Improving practice through collaboration: Early experiences from the multi-site Spinal Cord Injury Implementation and Evaluation Quality Care Consortium.

CONTEXT: Dedicated implementation efforts are critical to bridging the gaps between current practices and best practices. A quality improvement collaborative (QIC), the Spinal Cord Injury Implementation and Evaluation Quality Care Consortium (SCI IEQCC), was established to meet this need, bringing together a network of clinicians and administrators to systematically improve the quality and equity of tertiary spinal cord injury or disease (SCI/D) rehabilitation care in Ontario, Canada. METHODS: Clinicians and leaders from five tertiary SCI/D rehabilitation centers and two not-for-profit SCI/D advocacy groups comprised a network dedicated to supporting implementation of the SCI-High quality indicators in prioritized domains of SCI rehabilitation and related best practices by: (1) building capacity through implementation science education of frontline clinicians; (2) providing resources and support to empower frontline clinicians to lead quality improvement efforts within their institutions; (3) promoting wider learning through a network for sharing ideas, efforts, and experiences; and (4) collecting indicator data to facilitate provincial evaluation of goal attainment. RESULTS: Network members and sites collaborated to implement best practices within six priority domains; in 18 months, significant progress has been made in emotional wellbeing, sexual health, walking, and wheeled mobility despite disruptions due to the COVID-19 pandemic. These efforts encompass heterogeneous challenges and strategies, ranging from developing clinical skills programs, to streamlining processes, to manipulating physical space. CONCLUSION: A QIC targeting SCI/D rehabilitation demonstrates promise for advancing the implementation of best practices, building implementation science capacity across multiple sites, and for promoting collaboration amongst SCI/D rehabilitation centers and organizational partners.

Machine learning method for predicting pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: An accurate assessment of permanent pacemaker implantation (PPI) risk following transcatheter aortic valve replacement (TAVR) is important for clinical decision making. The aims of this study were to investigate the significance and utility of pre- and post-TAVR ECG data and compare machine learning approaches with traditional logistic regression in predicting pacemaker risk following TAVR. METHODS: Five hundred fifity seven patients in sinus rhythm undergoing TAVR for severe aortic stenosis (AS) were included in the analysis. Baseline demographics, clinical, pre-TAVR ECG, post-TAVR data, post-TAVR ECGs (24 h following TAVR and before PPI), and echocardiographic data were recorded. A Random Forest (RF) algorithm and logistic regression were used to train models for assessing the likelihood of PPI following TAVR. RESULTS: Average age was 80 ± 9 years, with 52% male. PPI after TAVR occurred in 95 patients (17.1%). The optimal cutoff of delta PR (difference between post and pre TAVR PR intervals) to predict PPI was 20 ms with a sensitivity of 0.82, a specificity of 0.66. With regard to delta QRS, the optimal cutoff was 13 ms with a sensitivity of 0.68 and a specificity of 0.59. The RF model that incorporated post-TAVR ECG data (AUC 0.81) more accurately predicted PPI risk compared to the RF model without post-TAVR ECG data (AUC 0.72). Moreover, the RF model performed better than logistic regression model in predicting PPI risk (AUC: 0.81 vs. 0.69). CONCLUSIONS: Machine learning using RF methodology is significantly more powerful than traditional logistic regression in predicting PPI risk following TAVR.

Use of CGRP receptor blocker erenumab in the management of post-traumatic headache: a case series of 5 women.

CONTEXT: Post-traumatic headache (PTH) is a disabling headache disorder and the most common sequela of mild traumatic brain injury. The pathophysiology of PTH is poorly understood and there is limited available evidence to guide prophylactic medication selection. Emerging understanding of the pathophysiology of migraine headaches has led to the development of monoclonal antibodies, including erenumab. Erenumab has shown promise for the prevention of primary migraine headache; however, it has not yet been studied in PTH. CASE SERIES: five women (average age 43.0 ± 17.9y) received treatment with erenumab for PTH secondary to mTBI. The average duration of PTH prior to starting erenumab was 32.0 ± 18.2 months. All patients were taking at least one daily headache prophylactic therapy prior to erenumab. The average pre-erenumab headache intensity was 86/100. On erenumab, the average reported reduction in headache intensity was 51.1%. After starting erenumab, all five patients were able to discontinue one or more medication(s). The most common side effect was constipation (three patients). There were no serious adverse events after an average follow-up of 3.4 ± 1.5 months. One patient discontinued erenumab during this period of follow-up after the resolution of her headaches. CONCLUSION: Erenumab appears to be safe and effective for the management of PTH.

The GLP-2 analogue elsiglutide reduces diarrhoea caused by the tyrosine kinase inhibitor lapatinib in rats.

PURPOSE: Lapatinib is a small molecule tyrosine kinase inhibitor used to treat breast cancer, often in combination with chemotherapy. Diarrhoea commonly occurs in up to 78% of patients undertaking lapatinib treatment. The mechanism of this diarrhoea is currently unknown. Elsiglutide is a GLP-2 analogue known to increase cell proliferation and reduce apoptosis in the intestine. METHODS: We used a previously developed rat model of lapatinib-induced diarrhoea to determine if co-treatment with elsiglutide was able to reduce diarrhoea caused by lapatinib. Additionally, we analysed the caecal microbiome of these rats to assess changes in the microbiome due to lapatinib. RESULTS: Rats treated with lapatinib and elsiglutide had less severe diarrhoea than rats treated with lapatinib alone. Serum lapatinib levels, blood biochemistry, myeloperoxidase levels and serum limulus amebocyte lysate levels were not significantly different between groups. Rats treated with lapatinib alone had significantly higher histopathological damage in the ileum than vehicle controls. This increase was not seen in rats also receiving elsiglutide. Rats receiving lapatinib alone had lower microbial diversity than rats who also received elsiglutide. CONCLUSIONS: Elsiglutide was able to reduce diarrhoea from lapatinib treatment. This does not appear to be via reduction in inflammation or barrier permeability, and may be due to thickening of mucosa, leading to increased surface area for fluid absorption in the distal small intestine. Microbial changes seen in this study require further research to fully elucidate their role in the development of diarrhoea.