The Validity, Reliability, Measurement Error, and Minimum Detectable Change of the 30‐Second Fast‐Paced Walk Test in Persons with Knee Osteoarthritis: A Novel Test of Short‐Distance Walking Ability

Objective To develop and establish the reliability, validity, measurement error, and minimum detectable change of a novel 30‐second fast‐paced walk test (30SFW) in persons with knee osteoarthritis (OA) that is easy to administer and can quantify walking performance in persons of all abilities. Methods Twenty females with symptomatic knee OA (mean age [SD] 58.30 [8.05] years) and 20 age‐ and sex‐matched asymptomatic controls (57.25 [8.71] years) participated in the study. Participants completed questionnaires of demographic and clinical data, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 36‐item Short Form Health Survey (SF‐36) followed by 30SFW performance. Participants returned 2‐7 days later and performed the 30SFW again. Results The knee OA group reported function that was worse than controls (all KOOS subscales; P \u3c 0.0001). The 30SFW intrarater and interrater reliability were excellent [ICC(2,1) = 0.95‐0.99]. Knee OA participants walked a shorter distance in the 30SFW than controls (mean [SD]: OA 44.4 m [9.5 m]; control 58.1 m [7.8 m]; P \u3c 0.0001). Positive strong correlations were found between the 30SFW and the KOOS–Activity of Daily Living, SF‐36‐Physical Functioning, and SF‐36‐Physical Health Composite scores (P \u3c 0.0001). A nonsignificant, weak correlation between 30SFW and SF‐36‐Mental Health scores was present (r = 0.32, P = 0.05). Conclusion The 30SFW has excellent intrarater and interrater reliability. The 30SFW demonstrated excellent known groups, convergent, and discriminant validity as a measure of short‐distance walking ability in persons with knee OA. Clinicians and researchers should consider using the 30SFW to quantify walking ability in persons with knee OA and assess walking ability change

Using the Oxford cognitive screen to detect cognitive impairment in stroke patients. A comparison with the Mini-Mental State Examination

Background: The Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive de cits after stroke. The scale consists of 10 tasks encom- passing ve cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive de cits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients. Objective: The present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine perfor- mance on the OCS as a function of subtypes of cerebral infarction and clinical severity. Methods: 325 rst stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classi cation and NIHSS, were given according to standard procedures. results: About a third of patients (35.3%) had a performance lower than the cutoff (<22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories. conclusion: Overall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive de cits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive pro ling.Background: The Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive deficits after stroke. The scale consists of 10 tasks encompassing five cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive deficits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients. Objective: The present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine performance on the OCS as a function of subtypes of cerebral infarction and clinical severity. Methods: 325 first stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classification and NIHSS, were given according to standard procedures. Results: About a third of patients (35.3%) had a performance lower than the cutoff(< 22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories. Conclusion: Overall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive deficits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive profiling. © 2018 Mancuso, Demeyere, Abbruzzese, Damora, Varalta, Pirrotta, Antonucci, Matano, Caputo, Caruso, Pontiggia, Coccia, Ciancarelli, Zoccolotti and The Italian OCS Grou

Continuous Glucose Monitoring Metrics for Earlier Identification of Pre-Diabetes: Protocol for a Systematic Review and Meta-Analysis

Introduction: Glycaemic variability and other metrics are not well characterised in subjects without diabetes. More comprehensive sampling as obtained with continuous glucose monitoring (CGM) may improve diagnostic accuracy of the transition from health to pre-diabetes. Our goal is to investigate the glycaemic system as it shifts from health to pre-disease in adult patients without diabetes using CGM metrics. New insights may offer therapeutic promise for reversing dysglycaemia more successfully with dietary, nutritional and lifestyle change before progression occurs to pre-diabetes and diabetes. Methods and analysis: This systematic review will include comprehensive searches of the PubMed, Scopus, Cochrane Library and ClinicalTrials.gov databases, with restrictions set to studies published in the last 10 years in English and planned search date 10 March 2022. Reference lists of studies that meet eligibility criteria in the screening process will subsequently be screened for the potential inclusion of additional studies. We will include studies that examine CGM use and report diagnostic criteria such as fasting glucose and/or haemoglobin A1c such that we can assess correlation between CGM metrics and established diagnostic criteria and describe how CGM metrics are altered in the transition from health to pre-diabetes. The screening and data extraction will be conducted by two independent reviewers using Covidence. All included papers will also be evaluated for quality and publication bias using Cochrane Collaboration risk of bias tools. If there are two or more studies with quantitative estimates that can be combined, we will conduct a meta-analysis after assessing heterogeneity. Ethics and dissemination: The systematic review methodology does not require formal ethical review due to the nature of the study design. Study findings will be publicly available and published in a peer-reviewed journal. Prospero registration number: CRD42022308222

A Cross-Sectional Study Evaluating the Impact of One Year versus Two Years of Exposure to Interprofessional Education on Student Perceptions of Physician-Pharmacist Interprofessional Clinical Education (SPICE)

Background: Evaluating student perceptions of interprofessional education (IPE) is important to meet accreditation standards. The objective of this study was to evaluate the impact of one year versus two years of exposure to IPE on student perceptions, as well as evaluate differences between professions. Methods: In this cross-sectional study, first and second year medical and pharmacy students enrolled in an interprofessional experiential course series at each of their respective institutions completed a perceptions instrument prior to a standardized objective behavioral assessment. Student demographics and perception scores were summarized using descriptive statistics. Chi-squared tests and Cochran-Mantel-Haenszel tests were used to assess differences in demographic variables. Between-group differences in perception scores were assessed using Wilcoxon Rank-Sum tests. Results: 155 students completed the instrument out of the 163 students enrolled in the course series. Overall, the median scores were ≥4 (4=Agree, 5=Strongly Agree) for all SPICE items and factors. No significant differences were observed between first and second year students in response to any of the SPICE items or factors. When comparing professions, significant differences were observed between pharmacy students and medical students that IPE “enhances my education” (p=0.003), “improves patient satisfaction” (p=0.001), and “enhances my future ability to collaborate” (p=0.001). Significant differences were also observed between pharmacy students and medical students for 2 of the 3 factors: teamwork (p=0.001) and patient outcomes (p=0.005). For all of the differences in items and factors, pharmacy students reported higher levels of agreement. Conclusions: Two years of exposure to IPE compared to one year (i.e. second year students vs. first year students) did not result in higher levels of agreement; however, agreement was high across all students which may have limited the ability to detect a difference. When perceptions are high early in the curriculum, maintaining the same level of agreement longitudinally may be a more appropriate educational outcome. Pharmacy students had higher levels of agreement compared to medical students for certain items. Further research is needed to determine if these differences have an impact on interprofessional collaboration. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Researc

A Cross-Sectional Study Evaluating the Impact of One Year versus Two Years of Exposure to Interprofessional Education on Student Perceptions of Physician-Pharmacist Interprofessional Clinical Education (SPICE)

Background: Evaluating student perceptions of interprofessional education (IPE) is important to meet accreditation standards. The objective of this study was to evaluate the impact of one year versus two years of exposure to IPE on student perceptions, as well as evaluate differences between professions. Methods: In this cross-sectional study, first and second year medical and pharmacy students enrolled in an interprofessional experiential course series at each of their respective institutions completed a perceptions instrument prior to a standardized objective behavioral assessment. Student demographics and perception scores were summarized using descriptive statistics. Chi-squared tests and Cochran-Mantel-Haenszel tests were used to assess differences in demographic variables. Between-group differences in perception scores were assessed using Wilcoxon Rank-Sum tests. Results: 155 students completed the instrument out of the 163 students enrolled in the course series. Overall, the median scores were ≥4 (4=Agree, 5=Strongly Agree) for all SPICE items and factors. No significant differences were observed between first and second year students in response to any of the SPICE items or factors. When comparing professions, significant differences were observed between pharmacy students and medical students that IPE “enhances my education” (p=0.003), “improves patient satisfaction” (p=0.001), and “enhances my future ability to collaborate” (p=0.001). Significant differences were also observed between pharmacy students and medical students for 2 of the 3 factors: teamwork (p=0.001) and patient outcomes (p=0.005). For all of the differences in items and factors, pharmacy students reported higher levels of agreement. Conclusions: Two years of exposure to IPE compared to one year (i.e. second year students vs. first year students) did not result in higher levels of agreement; however, agreement was high across all students which may have limited the ability to detect a difference. When perceptions are high early in the curriculum, maintaining the same level of agreement longitudinally may be a more appropriate educational outcome. Pharmacy students had higher levels of agreement compared to medical students for certain items. Further research is needed to determine if these differences have an impact on interprofessional collaboration. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Researc

When Eating Becomes Torturous: Understanding Nutrition-Related Cancer Treatment Side Effects among Individuals with Cancer and Their Caregivers

Individuals living with cancer often experience multiple nutrition-related side effects from cancer treatment, including changes in taste and smell, nausea, diarrhea, loss of appetite, and pain during eating. These side effects can profoundly impact nutritional status and quality of life. The purpose of this study was to explore experiences with nutrition-related cancer treatment side effects among cancer patients and their family caregivers, the way they manage such side effects, and the resulting changes in food preferences and behaviors. Structured surveys and in-depth interviews were conducted. Interviews focused on the presence and management of treatment side effects, how those changes influenced food preferences, and the extent to which they interfered with quality of life. Most patients (72%) reported treatment side effects; 61% reported that these side effects impacted their eating and drinking. Common side effects included fatigue (58%), dry mouth (30%), nausea (24%), constipation (20%) and diarrhea (20%). Six overarching qualitative themes were identified: Spiral of side effects; Pain of eating; Burden of eating; Loss of taste/change in taste; Symptom management; and Solutions. The authors conclude with implications for food and nutrition practice—moving beyond traditional recommendations of what to eat or avoid—to consider the overall patient and caregiver experience

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Using the Oxford Cognitive Screen to detect cognitive impairment in stroke patients: a comparison with the Mini-Mental State Examination

Background: The Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive deficits after stroke. The scale consists of 10 tasks encompassing five cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive deficits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients. Objective: The present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine performance on the OCS as a function of subtypes of cerebral infarction and clinical severity. Methods: 325 first stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classification and NIHSS, were given according to standard procedures. Results: About a third of patients (35.3%) had a performance lower than the cutoff (<22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories. Conclusion: Overall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive deficits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive profiling