ECFS standards of care on CFTR-related disorders: Towards a comprehensive program for affected individuals.

After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome.

There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics.

Use of intravaginal lactic acid bacteria prepartum as an approach for preventing uterine disease and its association with fertility of lactating dairy cows.

The objective of this study was to evaluate the effects of the use of intravaginal probiotics prepartum on the incidence risk of metritis postpartum and conception risk after first artificial insemination (AI). A total of 606 Holstein cows were enrolled 3 wk before their expected calving date from 2 farms. Cows were randomly assigned to either receive a 2-mL dose of a combination of 3 lactic acid bacteria (probiotic treatment) washed with approximately 2 mL of a sterile saline solution, into the vaginal canal twice weekly until parturition, or no intervention (control). Metritis diagnoses were carried out on 6 and 12 d postpartum. Vaginal discharge and rectal temperature were assessed, and vaginal discharge was scored on a scale from 1 to 4, where 1 = clear and 4 = fetid, purulent discharge. Metritis was defined as cows having a vaginal discharge score of 4 with or without fever (rectal temperature ≥39.5°C) on either 6 or 12 d postpartum, or both. Cows were bred after a 60-d voluntary waiting period primarily via the detection of estrus using automated activity monitors; cows not found in estrus were enrolled onto timed AI protocols to receive first breeding before 100 DIM. Pregnancy diagnosis was carried out at d 35 ± 7 post-AI on both farms. Data were analyzed via ANOVA using linear mixed regression models and survival analysis using a Cox proportional hazard model. Total incidence risk of metritis was 23.7% and 34.4% on farm A and farm B, respectively. Overall, the incidence of metritis was not different between treatment groups (control: 41.6 ± 3.8%; probiotic: 38.6 ± 4.0%); however, an interaction by farm was detected, where the probiotic treatment reduced metritis on one farm but not on the other. Conception risk after first AI was not affected by treatment. However, we detected an interaction between parity and treatment, where multiparous cows receiving the probiotic treatment were more likely to become pregnant compared with multiparous cows within the control group (hazard ratio: 1.33; 95% confidence interval: 1.10-1.60); no effect of probiotic treatment was found on the hazard of pregnancy for primiparous cows. In addition, the probiotic treatment was associated with an increased proportion of cows being detected in estrus for the first AI postpartum. In conclusion, vaginal probiotic treatment applied during the 3 wk prepartum was associated with a decreased incidence of metritis on one farm but not the other, suggesting that farm management may be a key player influencing treatment efficacy. Overall, probiotic treatment was found to have only limited effects on fertility in the current study.

Fatal non-accidental pediatric cranial fracture risk and three-layered cranial architecture development.

This study examines the influence of three-layered cranial architecture development upon blunt force trauma (BFT) cranial outcomes associated with pediatric non-accidental injury (NAI). Macroscopic and microscopic metric and morphological comparisons of subadult crania ranging from perinatal to 17 years of age chronicle the ontogenetic development and spatial and temporal variability in the emergence of a mature cranial architecture. Cranial vault thickness increases with subadult age, accelerating in the first 2 years of life due to rapid brain growth during this period. Three-layer differentiation of the cranial tables and diploë initiates by 3-6 months but is not consistently observed until 18 months to 2 years; diploë formation is not well developed until after age 4 and does not manifest a mature appearance until after age 8. These results allow topographic documentation of cortical and diploic development and temporal and spatial variability across the growing cranium. The lateral cranial vault is identified as expressing delayed development and reduced expression of the three-layer architecture, a pattern that continues into adulthood. Comparison of fracture locations from known BFT pediatric cases with identified cranial fracture high-risk impact regions shows a concordance and suggests the presence of a higher fracture risk associated with non-accidental BFT in the lateral vault region in subadults below the age of 2. The absence or lesser development of a three-layered architecture in subadults leaves their cranial bones, particularly in the lateral vault, thin and vulnerable to the effects of BFT.

Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia.

INTRODUCTION: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). METHODS: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. RESULTS: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. DISCUSSION: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. HIGHLIGHTS: We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline.

Clinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants.

Progressive supranuclear palsy causes diverse clinical presentations, including classical Richardson's syndrome and several variant phenotypes. Clinical trials of disease-modifying therapies have recently been completed, with more planned for the next 2 years. However, many people with progressive supranuclear palsy do not meet eligibility criteria for these clinical trials. Understanding clinical progression with different phenotypes would improve trial design and enhance the accuracy of risk-benefit and cost-benefit assessments of new treatments for progressive supranuclear palsy. We set out to determine rates of motor and cognitive progression of possible, probable and definite progressive supranuclear palsy, with different phenotypes, from a representative cohort in a regional UK healthcare service. Longitudinal clinical data from people with Richardson's syndrome and variant phenotypes were analysed using linear mixed-modelling, using both the full and modified versions of the Progressive Supranuclear Palsy Rating Scale, Mini-Mental State Examination and the revised Addenbrooke's Cognitive Examination. Subgroup analyses considered patients meeting recent Phase II trial entry criteria and patients with neuropathological confirmation. Two hundred and twenty-seven patients [male = 59%, mean age (±standard deviation), 71.8 (±7.0) years] were followed for a mean 21.6 (±15.6) months. One hundred and seventy-four (77%) had Richardson's syndrome at the outset, 25 had cortical variant presentations (13%, frontal, corticobasal, speech and language variants) and 28 had subcortical variant presentations (14%, parkinsonism, postural instability and gait freezing variants). Across all participants, annual progression in Richardson's syndrome was faster than variant phenotypes on the Mini-Mental State Examination (-1.8 versus -0.9/year, P = 0.005) and revised Addenbrooke's Cognitive Examination (-5.3 versus -3.0/year, P = 0.01) but not the Progressive Supranuclear Palsy Rating Scale (9.0 versus 7.1/year, P = 0.2) nor the modified Progressive Supranuclear Palsy Rating Scale (2.7 versus 2.3/year, P = 0.4). However, for those with more than 1 years' follow-up, a significant difference was observed between Richardson's syndrome and variant phenotypes in Progressive Supranuclear Palsy Rating Scale (8.7 versus 6.3/year, P = 0.04). Survival was longer in variant phenotypes than Richardson's syndrome [7.3 (±3.9) versus 5.6 (±2.0) years, P = 0.02]. Pathologically confirmed cases (n = 49) supported these findings. Patients meeting basic trial-eligibility criteria (n = 129) progressed faster on the Progressive Supranuclear Palsy Rating Scale than trial-not-eligible patients (10.1 versus 6.1/year, P = 0.001). In conclusion, phenotypes other than Richardson's syndrome show slower progression and longer survival. Trial criteria do not select representative progressive supranuclear palsy cases. This has implications for trial design, and application of trial results to clinically more diverse patient populations.

Clinical characteristics of two-hundred thirty-two dogs (2006-2018) treated for suspected anaphylaxis in Perth, Western Australia.

OBJECTIVE: To describe the clinical features of dogs treated for suspected anaphylaxis in Perth, Western Australia. DESIGN: Single-centre observational case series with retrospective and prospective phases. METHODS: This was a two-phase study of dogs with clinical suspicion of anaphylaxis presenting to the emergency service of a university teaching hospital. Dogs required evidence of, and appropriate treatment of, a type 1 hypersensitivity reaction as well as two or more organs affected (or cardiovascular signs alone) to be included. Phase 1 includes retrospective case series of 186 dogs (March 2006-December 2018). Phase 2 includes prospective descriptive case series of 46 dogs (October 2017-July 2018) focused on clinical signs. RESULTS: In phase 1, 88 (47%) dogs had evidence of insect exposure prior to the acute event. One hundred forty (75%) dogs had dermatological signs, 141 (76%) had gastrointestinal signs and 129 (69%) had cardiovascular signs. Ninety-two (49%) dogs had vasoconstrictive shock (5 with bradycardia), 24 (13%) had vasodilatory shock, 8 (4%) had mixed vasodilatory and vasoconstrictive shock and 5 (3%) had unclassifiable shock. On focused abdominal ultrasound, 42 of 71 (59%) dogs had gallbladder wall oedema and 3 of 71 (4%) dogs had peritoneal free fluid. In phase 2, the distributions of insect exposure, organ dysfunction and sonographic abnormalities were similar to phase 1. CONCLUSION: Dogs presenting with suspected anaphylaxis showed a broad range of presentations. Dermatological signs were absent in a proportion of dogs, vasoconstrictive shock was more frequent than vasodilatory and unique features of shock were identified. This study highlights the challenges of diagnosis based on presenting features alone.

Altered network stability in progressive supranuclear palsy.

The clinical syndromes of Progressive Supranuclear Palsy (PSP) may be mediated by abnormal temporal dynamics of brain networks, due to the impact of atrophy, synapse loss and neurotransmitter deficits. We tested the hypothesis that alterations in signal complexity in neural networks influence short-latency state transitions. Ninety-four participants with PSP and 64 healthy controls were recruited from two independent cohorts. All participants underwent clinical and neuropsychological testing and resting-state functional MRI. Network dynamics were assessed using hidden Markov models and neural signal complexity measured in terms of multiscale entropy. In both cohorts, PSP increased the proportion of time in networks associated with higher cognitive functions. This effect correlated with clinical severity as measured by the PSP-rating-scale, and with reduced neural signal complexity. Regional atrophy influenced abnormal brain-state occupancy, but abnormal network topology and dynamics were not restricted to areas of atrophy. Our findings show that the pathology of PSP causes clinically relevant changes in neural temporal dynamics, leading to a greater proportion of time in inefficient brain-states.

A survey of enteric organisms detected by real-time PCR assay in faeces of dogs in Western Australia.

This retrospective observational study reports the enteric organisms detected in dogs in Western Australia that had a faecal PCR (fPCR) submitted to a commercial veterinary laboratory. Of 2025 fPCR results, Clostridium perfringens alpha toxin gene was most frequently detected (87.2%), followed by Campylobacter spp. (37.8%), canine parvovirus (10.5%), Giardia spp. (9.7%), Salmonella spp. (7.0%), canine enteric coronavirus (2.3%), and canine distemper virus (0.3%). C.perfringens alpha toxin gene and Campylobacter spp. were the most common organisms co-detected. There was no statistically significant seasonal variation. Further studies are required to elucidate the role these organisms play in gastrointestinal disease in dogs.

Increasing facility delivery through maternity waiting homes for women living far from a health facility in rural Zambia: a quasi-experimental study.

OBJECTIVE: To report on the effectiveness of a standardised core Maternity Waiting Home (MWH) model to increase facility deliveries among women living >10 km from a health facility. DESIGN: Quasi-experimental design with partial randomisation at the cluster level. SETTING: Seven rural districts in Zambia. POPULATION: Women delivering at 40 health facilities between June 2016 and August 2018. METHODS: Twenty intervention and 20 comparison sites were used to test whether MWHs increased facility delivery for women living in rural Zambia. Difference-in-differences (DID) methodology was used to examine the effectiveness of the core MWH model on our identified outcomes. MAIN OUTCOME MEASURES: Differences in the change from baseline to study period in the percentage of women living >10 km from a health facility who: (1) delivered at the health facility, (2) attended a postnatal care (PNC) visit and (3) were referred to a higher-level health facility between intervention and comparison group. RESULTS: We detected a significant difference in the percentage of deliveries at intervention facilities with the core MWH model for all women living >10 km away (DID 4.2%, 95% CI 0.6-7.6, P = 0.03), adolescent women (<18 years) living >10 km away (DID 18.1%, 95% CI 6.3-29.8, P = 0.002) and primigravida women living >10 km away (DID 9.3%, 95% CI 2.4-16.4, P = 0.01) and for women attending the first PNC visit (DID 17.8%, 95% CI 7.7-28, P < 0.001). CONCLUSION: The core MWH model was successful in increasing rates of facility delivery for women living >10 km from a healthcare facility, including adolescent women and primigravidas and attendance at the first PNC visit. TWEETABLE ABSTRACT: A core MWH model increased facility delivery for women living >10 km from a health facility including adolescents and primigravidas in Zambia.

Reopening Oral Health Services during the COVID-19 Pandemic through a Knowledge Exchange Coalition.

BACKGROUND: The COVID-19 novel coronavirus closed oral health care in Nova Scotia (NS) Canada in March 2020. Preparing for a phased reopening, a knowledge exchange coalition (representing government, academia, hospitals, oral health professions, and regulators) developed return-to-work (RTW) guidelines detailing the augmentation of standard practices to ensure safety for patients, oral health care providers (OHPs), and the community. Using online surveys, this study explored the influence of the RTW guidelines and related education on registered NS OHPs during a phased return to work. METHODS: Dissemination of R2W guidelines included website or email communiques and interdisciplinary education webinars that coincided with 2 RTW phases approved by the government. Aligned with each phase, all registered dentists, dental hygienists, and dental assistants were invited to complete an online survey to gauge the influence of the coalition-sponsored education and RTW guidelines, confidence, preparedness, and personal protective equipment use before and after the pandemic. RESULTS: Three coalition-sponsored multidisciplinary webinars hosted 3541 attendees prior to RTW. The response to survey 1 was 41% (881/2156) and to survey 2 was 26% (571/2177) of registrants. Survey 1 (82%) and survey 2 (89%) respondents "agreed/strongly agreed" that R2W guidelines were a primary source for guiding return to practice, and most were confident with education received and had the skills needed to effectively treat patients during the COVID-19 pandemic. Confidence and preparedness improved in survey 2. Gowns/lab coat use for aerosol-generating procedures increased from 26% to 93%, and the use of full face shields rose from 6% to 93% during the pandemic. CONCLUSIONS: A multistakeholder coalition was effective in establishing and communicating comprehensive guidelines and web-based education to ensure unified reintegration of oral health services in NS during a pandemic. This multiorganizational cooperation lay the foundation for responses to subsequent waves of COVID-19 and may serve as an example for collaboratively responding to future public health threats in other settings. KNOWLEDGE TRANSFER STATEMENT: The return-to-work strategy that was developed, disseminated, and assessed through this COVID-19 knowledge exchange coalition will benefit oral health practitioners, professional regulators, government policy makers, and researchers in future pandemic planning.

Faecal PCR panel results and clinical findings in Western Australian dogs with diarrhoea.

AIM: To describe faecal PCR (fPCR) results and clinical findings of dogs seen at a university teaching hospital for diarrhoea. DESIGN: Retrospective case series (April 2015 to July 2018). PROCEDURE: Data were collected from the hospital electronic medical records. Data extracted included signalment, history, clinical signs, treatment, fPCR panel results, other faecal diagnostic test results and antimicrobial use. RESULTS: One hundred and sixty-eight dogs with diarrhoea had a fPCR panel submitted. Most dogs (115, 68.5%) had diarrhoea of 3 days or less duration. Clostridium perfringens alpha toxin gene was most frequently detected (156, 92.9%) by fPCR, followed by Campylobacter spp. (55, 32.7%), canine parvovirus (CPV) (29, 17.3%), Salmonella spp. (14, 8.3%) and Giardia spp. (9, 5.4%). For the 45 dogs that had a negative point-of-care CPV test, 13 were CPV fPCR positive; some of which were adult dogs with current vaccination status. A total of 94/168 (56%) dogs received antimicrobials at some time during the treatment of diarrhoea. CONCLUSION: Faecal PCR panels can identify dogs with enteric organisms in their faeces that traditional faecal diagnostics may miss, thus contributing additional information to the diagnostic process. Nonetheless, fPCR results should be interpreted in light of the clinical findings, and particular consideration given to avoiding inappropriate use of antimicrobials. This study highlights that testing for C. perfringens alpha toxin gene is not likely to be diagnostically helpful, and that adult dogs with diarrhoea might be identified as CPV positive with PCR testing, despite a negative point-of-care CPV test result and a current vaccination status.

Obstructive shock caused by right atrial thrombosis secondary to malignant pheochromocytoma in a dog.

BACKGROUND: Obstructive shock can be caused by any lesion leading to extraluminal compression or intraluminal occlusion of the cardiac chambers or major vessels. CASE REPORT: A 12-year-old, male castrated, Border Collie cross dog presented to a veterinary teaching hospital for collapse. A physical examination revealed severe vasoconstrictive shock and abdominal distension. Abnormalities on blood tests were consistent with systemic hypoperfusion. Cardiac underfilling, hepatomegaly with distended vasculature and ascites were identified by focused ultrasonography, raising suspicion of obstructive shock. This was supported by the radiographic findings of microcardia and a distended caudal vena cava (CVC). There was transient response to fluid therapy for blood volume expansion. Repeat focused ultrasonography during rapid intravenous fluid administration identified a right intra-atrial mass, assessed as likely to be causing obstruction of venous return. The dog was humanely euthanased given the guarded prognosis. At postmortem evaluation, a malignant pheochromocytoma in the left adrenal gland with tumour thrombus extending to the tricuspid valve through the CVC was found. The extensive thrombus caused the obstructive shock in this case. Metastasis in a peripheral lymph node and neoplastic emboli in the heart and lungs were also visible at the histopathological evaluation. CONCLUSION: To the best of authors' knowledge, this is the first report of severe obstructive shock secondary to extension of caval tumour thrombus into the right atrium in a dog with malignant pheochromocytoma. Tumour thrombus from a malignant pheochromocytoma should be included as a differential diagnosis of obstructive shock, with or without a visible right intra-atrial mass, in dogs. Serial focused ultrasonography during intravenous fluid administration can aid diagnosis.

Intramyocardial haematoma causing right ventricular outflow obstruction after brown snake (Pseudonaja species) envenomation in a dog.

A 15-month-old, male neutered Staffordshire Bull Terrier cross was presented to its referring veterinarian collapsed and agonal. He was immediately intubated, manually ventilated, and treatment commenced for presumptive snake envenomation with two vials of Tiger/Multi-Brown Snake Antivenom (minimum 7000 units/vial). The dog was transferred to a referral hospital intubated. Additional diagnostics performed following arrival at the referral hospital included a urine snake venom detection kit test, which was positive for brown snake immunotype. Three additional vials of Tiger/Multi-Brown Snake Antivenom (minimum 7000 units/vial) were administered until the dog was extubated and able to stand. Venom-induced consumptive coagulopathy (VICC) was diagnosed based on prolonged clotting times and scleral haemorrhage. Paroxysms of right ventricular outflow tract (RVOT) origin ventricular arrhythmias were treated with lignocaine and sotalol. Four days after presentation, a new-grade IV/VI systolic heart murmur was auscultated, prompting an echocardiogram. An anechoic and compartmentalised mass measuring 43 mm × 19 mm was visualized within the right ventricular wall at the RVOT, immediately adjacent to the pulmonic valve. The mass was causing a RVOT obstruction. Its appearance was suggestive of an intramyocardial haematoma, most likely secondary to VICC. The dog remained cardiovascularly stable, and treatment consisted of supportive care. Recheck echocardiograms at 2 and 7 weeks after discharge revealed progressive improvement of the intramyocardial mass and resolution of the associated heart murmur. Although intramyocardial haematomas are rare, it should be considered as a differential in dogs that develop a newly diagnosed heart murmur and/or cardiac arrhythmia following brown snake envenomation.

The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI. METHODS: With input from patients, family members, and clinicians, we developed and piloted a patient-centered, pragmatic intervention (OPTIMIZE) to educate and activate patients, family members, and primary care clinicians about deprescribing as part of optimal medication management for older adults with dementia or MCI and MCC. The clinic-based intervention targets patients on 5 or more medications, their family members, and their primary care clinicians using a pragmatic, cluster-randomized design at Kaiser Permanente Colorado. The intervention has two components: a patient/ family component focused on education and activation about the potential value of deprescribing, and a clinician component focused on increasing clinician awareness about options and processes for deprescribing. Primary outcomes are total number of chronic medications and total number of potentially inappropriate medications (PIMs). We estimate that approximately 2400 patients across 9 clinics will receive the intervention. A comparable number of patients from 9 other clinics will serve as wait-list controls. We have > 80% power to detect an average decrease of - 0.70 (< 1 medication). Secondary outcomes include the number of PIM starts, dose reductions for selected PIMs (benzodiazepines, opiates, and antipsychotics), rates of adverse drug events (falls, hemorrhagic events, and hypoglycemic events), ability to perform activities of daily living, and skilled nursing facility, hospital, and emergency department admissions. DISCUSSION: The OPTIMIZE trial will examine whether a primary care-based, patient- and family-centered intervention educating patients, family members, and clinicians about deprescribing reduces numbers of chronic medications and PIMs for older adults with dementia or MCI and MCC. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Alien limb in the corticobasal syndrome: phenomenological characteristics and relationship to apraxia.

Alien limb refers to movements that seem purposeful but are independent of patients' reported intentions. Alien limb often co-occurs with apraxia in the corticobasal syndrome, and anatomical and phenomenological comparisons have led to the suggestion that alien limb and apraxia may be causally related as failures of goal-directed movements. Here, we characterised the nature of alien limb symptoms in patients with the corticobasal syndrome (n = 30) and their relationship to limb apraxia. Twenty-five patients with progressive supranuclear palsy Richardson syndrome served as a disease control group. Structured examinations of praxis, motor function, cognition and alien limb were undertaken in patients attending a regional specialist clinic. Twenty-eight patients with corticobasal syndrome (93%) demonstrated significant apraxia and this was often asymmetrical, with the left hand preferentially affected in 23/30 (77%) patients. Moreover, 25/30 (83%) patients reported one or more symptoms consistent with alien limb. The range of these phenomena was broad, including changes in the sense of ownership and control as well as unwanted movements. Regression analyses showed no significant association between the severity of limb apraxia and either the occurrence of an alien limb or the number of alien limb phenomena reported. Bayesian estimation showed a low probability for a positive association between alien limb and apraxia, suggesting that alien limb phenomena are not likely to be related to severity apraxia. Our results shed light on the phenomenology of these disabling and as yet untreatable clinical features, with relevance to theoretical models of voluntary action.

Impact of the take ACTION Train-the-Trainer model of opioid overdose education with naloxone distribution- who benefits?

BACKGROUND: Overdose education with naloxone distribution (OEND) is a key national strategy to reduce morbidity and mortality related to opioid overdoses. Train-the-trainer model has been one method to increase the pool of trainers to facilitate greater dissemination of OEND. This exploratory study seeks to (1) evaluate participant's change in knowledge and confidence, (2) examine if pre- and post-training test outcomes differed by occupation and level of experience, and (3) determine if train-the-trainer participants trained others 6 months later. Methods: Fifteen train-the-trainer sessions were delivered to staff from community organizations who served high-risk clients in four counties whose overdose death rates ranged from 11.2 to 32.8 per 100,000. Participants were administered pre- and post-training tests from September 2017 to December 2018. A follow-up survey was conducted 6 months post-training to evaluate outcomes. Final paired pre-and post-training surveys of 109 participants were used for analysis. Paired sample t-tests were used to evaluate changes in the knowledge and confidence in teaching others. One-way ANOVA compared the change scores across groups with different demographic or experiential characteristics. Kruskal-Wallis Test was used for Likert scales. Results: The one and one-half hour train-the-trainer curriculum increased participants' knowledge and confidence to teach others (p < .001). This was particularly true for participants who had no prior experience compared to those who had some experience with naloxone (p = .0003). Changes in confidence to teach others significantly improved among demographic subgroups of participants. At 6 months after completing the train-the-trainer curriculum, 14 participants had trained 243 new trainees. Conclusions: Implementing a train-the-trainer model for OEND increases knowledge and participants' confidence to teach others. This demonstrates the important potential of the train-the-trainer model to respond to the growing opioid overdose epidemic.

The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy.

BACKGROUND: Studies on early-onset presentations of progressive supranuclear palsy (PSP) have been limited to those where a rare monogenic cause has been identified. Here, we have defined early-onset PSP (EOPSP) and investigated its genetic and clinico-pathological profile in comparison with late-onset PSP (LOPSP) and Parkinson's disease (PD). METHODS: We included subjects from the Queen Square Brain Bank, PROSPECT-UK study, and Tracking Parkinson's study. Group comparisons of data were made using Welch's t-test and Kruskal-Wallis analysis of variance. EOPSP was defined as the youngest decile of motor age at onset (≤55 years) in the Queen Square Brain Bank PSP case series. RESULTS: We identified 33 EOPSP, 328 LOPSP, and 2000 PD subjects. The early clinical features of EOPSP usually involve limb parkinsonism and gait freezing, with 50% of cases initially misdiagnosed as having PD. We found that an initial clinical diagnosis of EOPSP had lower diagnostic sensitivity (33%) and positive predictive value (38%) in comparison with LOPSP (80% and 76%) using a postmortem diagnosis of PSP as the gold standard. 3/33 (9%) of the EOPSP group had an underlying monogenic cause. Using a PSP genetic risk score (GRS), we showed that the genetic risk burden in the EOPSP (mean z-score, 0.59) and LOPSP (mean z-score, 0.48) groups was significantly higher (P < 0.05) when compared with the PD group (mean z-score, -0.08). CONCLUSIONS: The initial clinical profile of EOPSP is often PD-like. At the group level, a PSP GRS was able to differentiate EOPSP from PD, and this may be helpful in future diagnostic algorithms. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Effect of caffeinated gum on a battery of rugby-specific tests in trained university-standard male rugby union players.

BACKGROUND: Caffeine has been shown to enhance strength, power and endurance, characteristics that underpin performance in rugby. Caffeinated gum has attracted interest as a novel vehicle for delivering caffeine, because absorption of caffeine from gum is quick. Rapid absorption of caffeine may be useful during rugby matches when there is limited time for supplementation such as at half-time or when substitutes enter play. The purpose of this study was to determine whether a low dose of caffeine in gum improves performance in a battery of rugby-specific tests. METHODS: In a double-blind, randomized, placebo-controlled, crossover design, 17 male university-standard rugby players (mass: 85.6 ± 6.3 kg; height: 179.4 ± 6.2 cm; age: 20.4 ± 1.2 years) chewed caffeinated gum (200 mg caffeine) or a placebo gum on two occasions separated by a week. After a standardized warm-up, gum was chewed for 5 min. Subsequently, participants performed three countermovement jumps, followed by an Illinois agility test, 6 × 30 m repeated sprints, and the Yo-Yo IR-2 test; each test was separated by short rest periods. RESULTS: Caffeinated gum enhanced countermovement jump by 3.6% (caffeine: 43.7 ± 7.6 cm vs. placebo: 42.2 ± 6.2 cm; d = 0.22, 95% CI [0.006, 0.432]; p = 0.044). There was a greater resistance to fatigue during the 6 × 30 m repeated sprint test (fatigue index caffeine: 102.2 ± 0.9% vs. placebo: 103.3 ± 1.2%; d = 1.03, 95% CI [0.430, 1.613]; p = 0.001), and performance on the Yo-Yo IR2 was improved by 14.5% (caffeine: 426 ± 105 m, placebo: 372 ± 91 m; d = 0.55, 95% CI [0.130, 0.957]; p = 0.010). Caffeine gum had no significant effect on the Illinois agility test (caffeine 16.22 ± 1.08 s vs. placebo 15.88 ± 1.09 s; d = - 0.31, 95% CI [- 0.855, 0.240]; p = 0.271). CONCLUSIONS: In university-standard rugby players, a low dose of caffeine (200 mg) supplied in chewing gum enhanced performance on the Yo-Yo IR-2 test and the countermovement jump test and reduced fatigue index during repeated sprints. These improvements in a battery of rugby-specific tests may transfer to enhanced performance in rugby matches.

Quality of care assessment for people with multimorbidity.

Multimorbidity, the simultaneous presence of multiple health conditions in an individual, is an increasingly common phenomenon globally. The systematic assessment of the quality of care delivered to people with multimorbidity will be key to informing the organization of services for meeting their complex needs. Yet, current assessments tend to focus on single conditions and do not capture the complex processes that are required for providing care for people with multimorbidity. We conducted a scoping review on quality of care and multimorbidity in selected databases in June 2018 and identified 87 documents as eligible for review, predominantly original research and reviews from North America, Europe and Australasia and mostly frequently related to primary care settings. We synthesized data qualitatively in terms of perceived challenges, evidence and proposed metrics. Findings reveal that the association between quality of care and multimorbidity is complex and depends on the conditions involved (quality appears to be higher for those with concordant conditions, and lower in the presence of discordant conditions) and the approach used for measuring quality (quality appears to be higher in people with multimorbidity when measured using condition/drug-specific process or intermediate outcome indicators, and worse when using patient-centred reports of experiences of care). People with discordant multimorbidity may be disadvantaged by current approaches to quality assessment, particularly when they are linked to financial incentives. A better understanding of models of care that best meet the needs of this group is needed for developing appropriate quality assessment frameworks. Capturing patient preferences and values and incorporate patients' voices in the form of patient-reported experiences and outcomes of care will be critical towards the achievement of high-performing health systems that are responsive to the needs of people with multimorbidity.