Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

BACKGROUND: Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). METHODS: De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N = 2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N = 1098 (48%)] were identified to create longitudinal data for N = 204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. RESULTS: In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. CONCLUSIONS: Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

Blood Product Utilization in Patients With COVID-19 on ECMO.

INTRODUCTION: Although extracorporeal membrane oxygenation (ECMO) has been associated with improved outcomes in COVID patients with respiratory failure, data regarding the need for blood product utilization in this population is inadequate. METHODS: We conducted a retrospective review of all COVID patients requiring ECMO support at our facility. Patient demographics, co-morbidities, measures of acuity, and blood product utilization were identified. Patients were stratified by the presence of a major bleed and the need for dialysis. The primary outcome was blood product utilization. Linear regression models were used to assess predictors of the need for blood products. RESULTS: From 2020 to 2021, 41 patients with COVID-19 were included in our study. Overall 1601 d of support, COVID ECMO patients received 755 units of packed red blood cells (PRBC), 51 units of fresh frozen plasma (FFP), 326 platelets, and 1702 cryoprecipitate, amounting to 18.4 units PRBC per patient or 3.30 units per week of ECMO support. Both major bleeding and the need for dialysis were associated with higher rates of transfusion of PRBC, FFP, and platelets. The average non-bleeding COVID ECMO patient who did not need dialysis required 2.17 units of PRBC, 0.12 units of FFP, 0.76 platelets, and 8.36 of cryoprecipitate per week of ECMO support. On multivariable linear regression analysis, each day on ECMO was associated with 0.30 [0.19-0.42, P < 0.01] units of PRBC. CONCLUSIONS: In conclusion, COVID ECMO is associated with a significant need for blood and blood products. Major bleeding and dialysis are important drivers of blood product requirements.

Early mobilization in coronavirus-19 patients treated with extracorporeal membrane oxygenation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia can be associated with refractory respiratory failure requiring extracorporeal membrane oxygenation(ECMO). Although ECMO has helped many COVID patients, optimal management strategies for these patients remain unknown. METHODS: We conducted a retrospective review of all COVID patients requiring ECMO at our hospital. Six months into the pandemic, we changed our management strategy to focus on early mobilization. The early mobilization effort included tracheostomy within 48 h of cannulation, decreasing sedation, and an aggressive physical and occupational therapy program progressing toward early ambulation while on ECMO. The primary outcome measured was survival to discharge. The primary stratification was based on the mobilization strategy. RESULTS: From 2020 to 2021, 47 COVID patients have been supported with ECMO at our institution. Five are still in the hospital on ECMO. 39 (83%) were supported with venovenous ECMO while 8 (17%) were supported with venoarterial or a right ventricular assist device type configuration. All 47 (100%) were cannulated at bedside with transesophageal echocardiographic guidance. The average age was 47 ± 9 years; 36(77%) were male; and 20 (43%) were Hispanic. The median duration of support was 22 (11-44) days. Excluding those who remain in the hospital and on support, overall survival to discharge was 24/42 (57%). When stratified by mobilization strategy, early tracheostomy and mobilization were associated with significantly improved survival (74% [17/23] vs. 37% [7/19], p = .02). There were no changes in patient acuity or duration of support throughout the study period. CONCLUSION: In conclusion, early tracheostomy, decreased sedation, and aggressive mobilization of COVID-19 ECMO patients is associated with improved survival.

Intermediate-term survival and functional outcomes of COVID-19 extracorporeal membrane oxygenation patients.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been associated with acceptable short-term survival in patients with refractory respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia. Previous studies have demonstrated acceptable long-term outcomes in patients supported with ECMO for respiratory failure of other etiologies. However, long-term survival and functional outcomes in COVID ECMO patients remain unknown. METHODS: We conducted a retrospective review of all COVID patients requiring ECMO at our hospital. The primary outcomes measured were survival to discharge and contemporary survival. Secondary outcomes included two simple functional assessments: the ongoing need for oxygen supplementation and the ability to return to work. Survival was calculated using the Kaplan-Meier method. Hazard ratios were calculated using Cox hazards regression models. RESULTS: From 2020 to 2021, 48 COVID patients have been supported with ECMO at our hospital. Four patients remain on support and were excluded from further analysis. The average age was 47 ± 8 years, 34 (77%) were males, and the plurality (19, 43%) were Hispanic. Median duration of support was 23 (12-51) days. Median follow-up was 106 (29-226) days. Survival to discharge was 59%. Kaplan-Meier 180-day survival was 51%. Long-term survival conditioned on survival to discharge was 89%. In evaluating functional outcomes, the overwhelming majority of patients no longer required oxygen supplementation (74%), and most had returned to work (52%). CONCLUSION: In conclusion, COVID ECMO patients have acceptable intermediate-term survival with adequate functional recovery.

Social-emotional processing in nonverbal individuals with Angelman syndrome: evidence from brain responses to known and novel names.

BACKGROUND: The combination of intellectual, communicative and motor deficits limits the use of standardised behavioural assessments in individuals with Angelman syndrome (AS). The current study aimed to objectively evaluate the extent of social-emotional processing in AS using auditory event-related potentials (ERPs) during passive exposure to spoken stimuli. METHODS: Auditory ERP responses were recorded in 13 nonverbal individuals with the deletion subtype of AS, age 4-45 years, during the name recognition paradigm, in which their own names and names of close others (relative or friend) were presented among novel names. No behavioural responses were required. RESULTS: Contrary to findings in typical children and adults, there was no significant evidence of differential neural response to known vs. novel names in participants with AS. Nevertheless, greater amplitude differences between known and unknown names demonstrated the predicted association with better interpersonal relationships and receptive communication abilities. CONCLUSIONS: These findings indicate good tolerability of ERP procedures (85% success rate). The lack of own name differentiation is consistent with increased incidence of the autism-related symptoms in AS. Strong associations between the caregiver reports of adaptive functioning and neural indices of known name recognition support the utility of brain-based measures for objectively evaluating cognitive and affective processes in nonverbal persons with neurodevelopmental disorders.

Processing of stimulus content but not of emotional valence is altered in persons with Williams syndrome.

BACKGROUND: Individuals with Williams syndrome (WS) exhibit hypersociability and may respond atypically to emotional information in social and nonsocial stimuli. It is not yet clear whether these difficulties are specific to emotional content or stimulus type. This study examined the neural processes supporting social and emotional information processing in WS. METHOD: Visual event-related potentials were recorded in 19 adults with WS and 10 typical peers during a picture-viewing task requiring detection of smiling faces among other social and nonsocial images with positive and negative emotional content. RESULTS: The participant groups were not significantly different in affective processing of positive and negative stimuli and perceived faces as different from nonsocial images. Participants with WS showed subtle differences in face-specific perceptual processes (e.g. face inversion, N170 lateralisation), suggesting a more feature-based processing. They also demonstrated reduced attention and arousal modulation (P3, late positive potential) in response to faces vs. nonsocial images. These differences were independent of intelligence quotient. CONCLUSIONS: There was no evidence of greater than typical perceptual, attentional or affective processing of social information in WS. The results support the idea that altered face perception processes and not the increased salience of social stimuli or difficulties with emotion discrimination may contribute to the hypersocial phenotype in WS.

Consonant differentiation mediates the discrepancy between non-verbal and verbal abilities in children with ASD.

BACKGROUND: Many children with autism spectrum disorder (ASD) demonstrate verbal communication disorders reflected in lower verbal than non-verbal abilities. The present study examined the extent to which this discrepancy is associated with atypical speech sound differentiation. METHODS: Differences in the amplitude of auditory event-related potentials elicited by contrasting consonant-vowel syllables during a passive listening paradigm were used to assess speech sound differentiation in 24 children with ASD and 18 chronological age-matched children with typical development (TD), M age 6.90 years (SD = 1.39). RESULTS: Results revealed that compared with TD peers, children with ASD showed reduced consonant differentiation in the 84- to 308-ms period. Brain responses indexing consonant differentiation were negatively related to the degree of discrepancy in non-verbal and verbal abilities and mediated the relationship between diagnostic group membership and the greater discrepancy. CONCLUSIONS: We discuss the theoretical and clinical implications of the brain's response to speech sound contrasts possibly explaining the greater non-verbal versus language ability in children with ASD compared with that in typically developing children.

The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms--A blinded interventional study.

BACKGROUND: Perioperative beta-blockade is widely used, especially before vascular surgery; however, its impact on exercise performance assessed using cardiopulmonary exercise testing (CPET) in this group is unknown. We hypothesized that beta-blocker therapy would significantly improve CPET-derived physical fitness in this group. METHODS: We recruited patients with abdominal aortic aneurysms (AAA) of <5.5 cm under surveillance. All patients underwent CPET on and off beta-blockers. Patients routinely prescribed beta-blockers underwent a first CPET on medication. Beta-blockers were stopped for one week before a second CPET. Patients not routinely taking beta-blockers underwent the first CPET off treatment, then performed a second CPET after commencement of bisoprolol for at least 48 h. Oxygen uptake (.VO2) at estimated lactate threshold and .VO2 at peak were primary outcome variables. A linear mixed-effects model was fitted to investigate any difference in adjusted CPET variables on and off beta-blockers. RESULTS: Forty-eight patients completed the study. No difference was observed in .VO2 at estimated lactate threshold and .VO2 at peak; however, a significant decrease in .VE/.VCO2 at estimated lactate threshold and peak, an increase in workload at estimated lactate threshold., O2 pulse and heart rate both at estimated lactate threshold and peak was found with beta-blockers. Patients taking beta-blockers routinely (chronic group) had worse exercise performance (lower .VO2 ). CONCLUSIONS: Beta blockade has a significant impact on CPET-derived exercise performance, albeit without changing .VO2 at estimated lactate threshold and.VO2 at peak. This supports performance of preoperative CPET on or off beta-blockers depending on local perioperative practice. CLINICAL TRIAL REGISTRATION: NCT 02106286.

'Hungry Eyes': visual processing of food images in adults with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder associated with intellectual disabilities, compulsivity, hyperphagia and increased risks of life-threatening obesity. Food preferences in people with PWS are well documented, but research has yet to focus on other properties of food in PWS, including composition and suitability for consumption. It is also unclear how food perceptions differ across the two major genetic subtypes of PWS. METHODS: This study examined neural responses to food stimuli in 17 adults with PWS, nine with paternal deletions and eight with maternal uniparental disomy (UPD), and in nine age-matched typical controls. Visual event-related potentials (ERPs) were recorded in response to food images varying in food composition and suitability for consumption during a passive viewing paradigm. RESULTS: Group differences were observed for the N1 and P3 responses reflecting perceptual categorisation and motivational relevance respectively. The deletion group categorised food stimuli in terms of composition while the UPD group performed more similar to the controls, and focused on the suitability of food for consumption. Individual differences in N1 amplitude correlated with body mass index and scores on the Hyperphagia Questionnaire. CONCLUSION: Differences are seen in how people with PWS because of deletion or UPD perceive visual food stimuli even within the first milliseconds of stimuli exposure. Implications are discussed for in vivo food behaviours and for future ERP or neuroimaging studies on hunger, satiety and food perception in PWS.

Clinical reasoning of an experienced physiotherapist: insight into clinician decision-making regarding low back pain.

BACKGROUND AND PURPOSE: Investigation of the clinical reasoning skills of experienced clinicians provides insight into decision-making in the practice of physiotherapy. The purpose of the present study was to analyse the clinical reasoning skills of an experienced physiotherapist during her assessment and treatment of clients with low back pain. METHOD: Deconstruction of the physiotherapist's reasoning process was accomplished through observation of encounters between her and each of six patient subjects. Reconstruction and analysis of the physiotherapist's decision-making process was performed through retrospective interviews and reflective analysis of her clinical reasoning during each encounter. RESULTS: A working model of the physiotherapist's clinical reasoning was created from an integration of theoretical elements in the literature and the data. Through analysis of this framework, two core dimensions of her clinical reasoning were revealed: the influence of clinical experience and the influence of advanced training in a specific philosophy of treating the spine. CONCLUSIONS: The construction of these themes has contributed to the growing understanding of clinical reasoning strategies and skills used in orthopaedic physical therapy practice. Detailed description of the physiotherapist's reasoning process provides more meaningful understanding of physiotherapy treatments. In this case the physiotherapist employed a pattern recognition strategy and forward reasoning process in making a diagnosis. Further research is necessary to expand knowledge on the development of clinical reasoning skills.

Cervical spine dislocations with unilateral facet interlocking.

From this series it would appear that 17-5 per cent (92 cases from a series of 525) of all cervical lesions associated with spinal cord trauma are dislocations with unilateral facet interlocking. This type of dislocation is often missed but nevertheless with suitable radiographs the very characteristic radiographic appearances are well demonstrated. Two-thirds of these cases are initially incomplete neurological lesions which carry a good neurological prognosis directly proportional to the degree of initial neurological escape. A significant percentage reduce easily on traction alone--51 per cent of the entire series. Taking the year 1973, with 17 cases on a standardised regime of treatment and disregarding the two cases reduced by immediate manipulation under general anaesthesia, ten out of 15 (66 per cent) reduced easily on skull traction alone-possibly a more realistic figure.

Social reintegration of paraplegics and tetraplegics in the Cape Province of the Republic of South Africa.

Rehabilitation of the disabled is a dynamic process which should start from the first day post-injury. Total rehabilitation should include, not only attaining maximum function, but also, satisfaction with life in one's own environment. The obstacles created by able-bodied society, are problems that face the disabled person. The right to participate in, and contribute to, all aspects of economic, social and political life is theirs too, as is the right to make decisions about the future. This should not be overlooked, as decision making sows the seeds of motivation. This in turn dictates the measure of success of social reintegration. Assistance is provided in South Africa by various organisations of central government, provincial and local authorities and private welfare organisations. The Cripple Care Association is a private welfare organisation which provides assistance and acts as a link with other relevant organisations. In the Western Cape the number of successfully rehabilitated persons increases and their presence in the community creates an awareness of their needs. This in turn initiates the process of positive change and action.

Urological management of the patient with spinal cord injury.

A total of 515 patients with spinal cord injuries were admitted to the Conradie Hospital's Spinal Cord Injuries Centre during a 3-year period from September 1974 to September 1977. Intermittent catheterization was used for urinary drainage in all patients with incomplete lesions as initially assessed neurologically, and indwelling catheterization in those with complete lesions. Transcutaneous suprapubic Bonnano (stab) continuous catheter drainage was used in a random group of 24 male patients with complete neurological lesions. The majority of the patients were admitted within 24 hours of injury. The follow-up period varied from 1 to 4 years. At 3 months more than 50% of patients had a balanced neurogenic bladder and were catheter-free. At 12 months 19% of patients were still catheter-dependent for reasons explained. Bladder outlet operations were more frequent among patients with thoracic lesions and were indicated 3 times more often in patients with complete neurological lesions. Bladder outlet operations were performed on 8.6% of patients. Only 5 patients (1%) required permanent urinary diversion. A urodynamic work-up is no longer regarded as merely a research tool in the investigation of patients with neurogenic bladder dysfunction. Both urodynamic and videoradiological techniques are a prerequisite to proper management of the neurogenic urinary tract.

The effect of the Trendelenburg position on lower oesophageal sphincter tone.

Measurements were made of gastric, lower oesophageal and barrier pressures in the supine, moderate and steep Trendelenburg positions in 10 healthy female patients during balanced anaesthesia. Adoption of the Trendelenburg position resulted in no significant changes in any measurement, with the exception of a small increase (0.1 kPa) in intragastric pressure in the steep head-down position. We conclude that the steep Trendelenburg position should not predispose to regurgitation in healthy patients.

Pressure redistribution in wheelchair cushion for paraplegics: its application and evaluation.

A survey of the first 200 cases supplied with a "Paracare" pressure redistribution wheelchair cushion. The rationale of the design and material used is discussed. The method of application and follow-up studies are given and a total evaluation of the results achieved to date are presented.

Comparison of the combined effects of atropine and neostigmine with atropine and edrophonium on the lower oesophageal sphincter.

In two groups (n = 11) of healthy patients, we have measured gastric, lower oesophageal and barrier pressures before and after antagonism of neuromuscular block during anaesthesia with nitrous oxide and isoflurane. In one group, atropine 1.2 mg and neostigmine 2.5 mg were given and in the second group atropine 0.6 mg with edrophonium 1 mg/kg. One minute after administration of the reversal agents, there was a significantly greater reduction in barrier pressures in the neostigmine and atropine group than in the edrophonium and atropine group, but subsequently, there was no significant difference between the two groups. We conclude that there is no clinical difference between the two reversal mixtures in terms of the risk of regurgitation in the immediate period after reversal.

A functional splint for the C5 tetraplegic arm.

An orthosis for a C5 complete tetrapletic providing active extension and pronation of the forearm is presented. It overcomes and prevents the occurrence of the flexed and supinated C5 tetraplegic arms. Technical data and a case report is included.

The prevention and treatment of pressure sores in the sitting paraplegic.

Pressure sores in the sitting paraplegic patient can delay rehabilitation by weeks or months, or can lead to the patient's permanent confinement to bed. This paper describes a method of redistributing the pressure loading on the sitting area so that pressure sores are unlikely to occur. In addition, a clinical approach which increases the patient's awareness of the problem is outlined and case histories and clinical results are described.