Factor XIII levels, clot strength, and impact of fibrinogen concentrate in infants undergoing cardiopulmonary bypass: a mechanistic sub-study of the FIBCON trial.

BACKGROUND: Acquired factor XIII (FXIII) deficiency after major surgery can increase postoperative bleeding. We evaluated FXIII contribution to clot strength and the effect of fibrinogen concentrate administration on FXIII activity in infants undergoing cardiac surgery using cardiopulmonary bypass. METHODS: We conducted a prospectively planned, mechanistic sub-study, nested within the Fibrinogen Concentrate Supplementation in the Management of Bleeding During Paediatric Cardiopulmonary Bypass: A Phase 1B/2A, Open-Label Dose Escalation Study (FIBCON) trial, which investigated fibrinogen concentrate supplementation during cardiopulmonary bypass (ISRCTN: 50553029) in 111 infants (median age 6.4 months). The relationships between platelet number, fibrinogen concentration, and FXIII activity with rotational thromboelastometry clot strength (EXTEM-MCF) in blood taken immediately before cardiopulmonary bypass and after separation from bypass were estimated using multivariable linear regression. Changes in coagulation variables over time were quantified using a generalised linear model comparing three groups: fibrinogen concentrate-supplemented infants, placebo, and a third cohort with lower bleeding risk. RESULTS: Overall, 48% of the variability (multivariable R2) in EXTEM-MCF clot strength was explained by three factors: the largest contribution was from FXIII activity (partial R2=0.21), followed by platelet number (partial R2=0.14), and fibrinogen concentration (partial R2=0.095). During cardiopulmonary bypass, mean platelet count fell by a similar amount in the three groups (-36% to -41%; interaction P=0.98). Conversely, fibrinogen concentration increased in all three groups: 132% in the fibrinogen concentrate-supplemented group, 26% in the placebo group, and 51% in the low-risk group. A similar increase was observed for FXIII activity (61%, 23%, and 25%, respectively; interaction P<0.0001). CONCLUSIONS: FXIII contribution to clot strength is considerable in infants undergoing cardiac surgery. Fibrinogen concentrate supplementation also increased FXIII activity, and hence clot strength. CLINICAL TRIAL REGISTRATION: ISRCTN: 50553029.

Pediatric Cardiac Anesthesia Training and Staffing in the National Health Service.

BACKGROUND: Considerable importance is attached to the process of training, appointing and retaining highly specialized pediatric anesthetists, such as those with a congenital heart disease practice. AIMS: For the 10-year period from April 2012 to March 2022, we wished to establish changes in the absolute number of consultant pediatric cardiac anesthetic posts in NHS Level 1 Centres, turnover in such posts, and what training appointees had received. METHODS: An email survey was sent to the Centre Representative from the Congenital Cardiac Anesthesia Network in each of the eleven NHS Level 1 Pediatric Congenital Heart Disease Centre. Further follow up was completed in order to confirm accuracy of responses. We defined a pediatric cardiac anesthetist as a consultant with a clinical practice including provision of anesthetic management for children undergoing cardiac surgery incorporating the use of cardiopulmonary bypass. RESULTS: The response rate to our survey was 100%. Over the study period the number of consultants increased from 69 to 81, though three posts were unfilled as at March 2022. There were 55 departures and 65 appointees. Five consultants moved between NHS Units. 52 consultants received formal fellowship training and 13 switched into pediatric cardiac anesthesia from an existing general pediatric anesthetic post, with a period of supplementary training within their institution. Appointees reported extensive additional training variably including fellowships in general pediatric anesthesia, adult cardiac anesthesia and pediatric intensive care, both within and outside the United Kingdom. CONCLUSIONS: There has been both an expansion in the number of posts, as well as considerable turnover in consultant posts in the last 10 years. Training standards which support and guide individuals as they develop a practice in this highly specialized field should reflect different routes into the speciality and could be established with the support and advice of the Congenital Cardiac Anesthesia Network.

Predictive processing and perception: What does imagining have to do with it?

Predictive processing (PP) accounts of perception are unique not merely in that they postulate a unity between perception and imagination, but in claiming that (i) perception should be conceptualised in terms of imagination and (ii) the two involve an identity of neural implementation. This paper argues against these claims, on both conceptual and empirical grounds. Conceptually, the manner in which PP theorists link perception and imagination belies an impoverished account of imagery as cloistered from the external world in its intentionality, akin to a virtual reality, as well as endogenously generated. Yet this ignores a whole class of imagery whose intentionality is directed on the actual environment-projected mental imagery-and also ignores the fact that imagery may be triggered crossmodally in a bottom-up, stimulus-driven way. Empirically, claiming that imagery and perception share neural circuitry ignores relevant clinical results in this area. These evidence substantial perception/imagery neural dissociations, most notably in the case of aphantasia. Taken together, the arguments here suggest that PP theorists should substantially temper, if not outright abandon, their claim to a perception/imagination unity.

A nationwide evaluation study of the quality of care and respect of human rights in mental health facilities in Ghana: results from the World Health Organization QualityRights initiative.

BACKGROUND: In 2012, Ghana ratified the United Nations Convention on the Rights of Persons with Disabilities and enacted a Mental Health Act to improve the quality of mental health care and stop human rights violations against people with mental health conditions. In line with these objectives, Ghanaian stakeholders collected data on the quality of mental health services and respect for human rights in psychiatric facilities to identify challenges and gather useful information for the development of plans aimed to improve the quality of the services offered. This study aimed to assess psychiatric facilities from different Ghanaian regions and provide evidence on the quality of care and respect of human rights in mental health services. METHODS: Assessments were conducted by independent visiting committees that collected data through observation, review of documentation, and interviews with service users, staff, and carers, and provided scores using the World Health Organization QualityRights Toolkit methodology. RESULTS: This study revealed significant key challenges in the implementation of the United Nations Convention on the Rights of Persons with Disabilities principles in Ghanaian psychiatric services. The rights to an adequate standard of living and enjoyment of the highest attainable standard of health were not fully promoted. Only initial steps had been taken to guarantee the right to exercise legal capacity and the right to personal liberty and security. Significant gaps in the promotion of the right to live independently and be included in the community were identified. CONCLUSIONS: This study identifies shortcomings and critical areas that the Ghanaian government and facilities need to target for implementing a human rights-based approach in mental health and improve the quality of mental health care throughout the country.

Enabling precision medicine via standard communication of HTS provenance, analysis, and results.

A personalized approach based on a patient's or pathogen's unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to findable, accessible, interoperable, and reusable (FAIR) guiding principles. Moreover, effective precision medicine requires standardized reporting that extends beyond wet-lab procedures to computational methods. The BioCompute framework (https://w3id.org/biocompute/1.3.0) enables standardized reporting of genomic sequence data provenance, including provenance domain, usability domain, execution domain, verification kit, and error domain. This framework facilitates communication and promotes interoperability. Bioinformatics computation instances that employ the BioCompute framework are easily relayed, repeated if needed, and compared by scientists, regulators, test developers, and clinicians. Easing the burden of performing the aforementioned tasks greatly extends the range of practical application. Large clinical trials, precision medicine, and regulatory submissions require a set of agreed upon standards that ensures efficient communication and documentation of genomic analyses. The BioCompute paradigm and the resulting BioCompute Objects (BCOs) offer that standard and are freely accessible as a GitHub organization (https://github.com/biocompute-objects) following the "Open-Stand.org principles for collaborative open standards development." With high-throughput sequencing (HTS) studies communicated using a BCO, regulatory agencies (e.g., Food and Drug Administration [FDA]), diagnostic test developers, researchers, and clinicians can expand collaboration to drive innovation in precision medicine, potentially decreasing the time and cost associated with next-generation sequencing workflow exchange, reporting, and regulatory reviews.

Risk associated with anesthesia for noncardiac surgery in children with congenital heart disease.

Database analysis has indicated that perioperative cardiac arrest occurs with increased frequency in children with congenital heart disease. Several case series and large datasets from ACS NSQIP have identified subgroups at the highest risk. Consistently, patients with single ventricle physiology (especially prior to cavopulmonary anastomosis), severe/supra-systemic pulmonary hypertension, complex lesions, and cardiomyopathy with significantly reduced ventricular function have been shown to be at increased risk for adverse events. Based on these results, algorithms for assessing risk have been proposed. How hospitals and health care systems apply these guidelines to provide safe care for these challenging patient groups requires the application of modern quality improvement techniques. Each institution should develop a system which reflects local expertise and resources.

Inverting the deficit model in global mental health: An examination of strengths and assets of community mental health care in Ghana, India, Occupied Palestinian territories, and South Africa.

Global mental health [GMH] scholarship and practice has typically focused on the unmet needs and barriers to mental health in communities, developing biomedical and psychosocial interventions for integration into formal health care platforms in response. In this article, we analyse four diverse settings to disrupt the emphasises on health system weaknesses, treatment gaps and barriers which can perpetuate harmful hierarchies and colonial and medical assumptions, or a 'deficit model'. We draw on the experiential knowledge of community mental health practitioners and researchers working in Ghana, India, the Occupied Palestinian Territory and South Africa to describe key assets existing in 'informal' community mental health care systems and how these are shaped by socio-political contexts. These qualitative case studies emerged from an online mutual learning process convened between 39 academic and community-based collaborators working in 24 countries who interrogated key tenets to inform a social paradigm for global mental health. Bringing together diverse expertise gained from professional practice and research, our sub-group explored the role of Community Mental Health Systems in GMH through comparative country case studies describing the features of community care beyond the health and social care system. We found that the socio-political health determinants of global economic structures in all four countries exert significant influence on local community health systems. We identified that key assets across sites included: family and community care, and support from non-profit organisations and religious and faith-based organisations. Strengthening community assets may promote reciprocal relationships between the formal and informal sectors, providing resources for support and training for communities while communities collaborate in the design and delivery of interventions rooted in localised expertise. This paper highlights the value of informal care, the unique social structures of each local context, and resources within local communities as key existing assets for mental health.

Aphantasia and psychological disorder: Current connections, defining the imagery deficit and future directions.

Aphantasia is a condition characterized by a deficit of mental imagery. Since several psychopathologies are partially maintained by mental imagery, it may be illuminating to consider the condition against the background of psychological disorder. After outlining current findings and hypotheses regarding aphantasia and psychopathology, this paper suggests that some support for defining aphantasia as a lack of voluntary imagery may be found here. The paper then outlines potentially fruitful directions for future research into aphantasia in general and its relation to psychopathology in particular, including rethinking use of the SUIS to measure involuntary imagery, whether aphantasia offers protection against addiction, and whether hyperphantasia is a potential risk factor for maladaptive daydreaming, among others.

SnappySonic: An Ultrasound Acquisition Replay Simulator.

SnappySonic provides an ultrasound acquisition replay simulator designed for public engagement and training. It provides a simple interface to allow users to experience ultrasound acquisition without the need for specialist hardware or acoustically compatible phantoms. The software is implemented in Python, built on top of a set of open source Python modules targeted at surgical innovation. The library has high potential for reuse, most obviously for those who want to simulate ultrasound acquisition, but it could also be used as a user interface for displaying high dimensional images or video data.

The influence of hyperchloraemia on acid base interpretation in diabetic ketoacidosis.

OBJECTIVES: During the acute treatment of diabetic ketoacidosis we (a) determined the temporal incidence of hyperchloraemia, and (b) quantified the influence of hyperchloraemia on interpretation of common blood gas derived acid base parameters, namely base deficit and bicarbonate. DESIGN AND SETTING: Retrospective chart review in two regional paediatric intensive care units. MEASUREMENTS AND RESULTS: Stewart's physicochemical theory was used to develop regression equations quantifying the acidifying effect of hyperchloraemia on both base deficit and bicarbonate. These were then applied retrospectively to blood chemistry results from 18 children (median age 12.7 years, weight 43 kg) with diabetic ketoacidosis. Plasma ketonaemia was estimated using the albumin-corrected anion gap. The incidence of hyperchloraemia, as documented by a ratio of plasma chloride to sodium of greater than 0.79, increased from 6% at admission to 94% after 20 h of treatment. Correction for chloride produced a dramatic improvement in the relationship between changes in the anion gap vs. both base deficit (from R(2)=0.55 to R(2)=0.95) and bicarbonate (from R(2)=0.51 to R(2)=0.96) during treatment. After 20 h of treatment the mean base deficit had decreased from 24.7 mmol/l to 10.0 mmol/l however, the proportion that was due to hyperchloraemia increased from 2% to 98%. CONCLUSIONS: It is now possible using a simple correction factor to quantify the confounding effect of hyperchloraemia on both base deficit and bicarbonate in diabetic ketoacidosis. This bedside tool may be a useful adjunct to guide therapeutic interventions.

Early application of generic mortality risk scores in presumed meningococcal disease.

OBJECTIVE: Mortality from meningococcal disease typically occurs within 24 hrs of intensive care unit (ICU) admission. An early, accurate mortality-risk tool may aid in trial design for novel therapies. We assessed the performance of two generic scores that assign mortality risk within 1 hr of ICU admission: the Preintensive Care Pediatric Risk of Mortality (Pre-ICU PRISM) and Pediatric Index of Mortality (PIM). DESIGN: Prospective, observational study over 21 months. SETTING: Two tertiary pediatric ICUs accepting referrals from southeast England. PATIENTS: Patients were 165 consecutive children with meningococcal disease. Ages ranged from 0.1 to 17 yrs (median 2.3 yrs). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PIM demonstrated greater sensibility, with complete data collected in 93% of cases, compared with 35% for the pre-ICU PRISM. Both scores discriminated well. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval, 0.81-1.00) for PIM and 0.94 (95% confidence interval, 0.88-0.98) for Pre-ICU PRISM; this did not change when applied to the subgroup of patients with complete data. Both scores calibrated poorly, overestimating mortality in the medium-risk strata (and also in the high-risk stratum in the case of Pre-ICU PRISM). When used as a stratification tool for a hypothetical trial (60% reduction in mortality, 80% power), the scores allowed for a reduction in study size by 50% (PIM) and 43% (pre-ICU PRISM). CONCLUSIONS: Pre-ICU PRISM and PIM both discriminate well but calibrate poorly when applied to a cohort of children with meningococcal sepsis. Both scores provide an effective means of stratification for clinical trial purposes. The main advantage for PIM appears to be ease of data collection.

Application of the core competencies after unexpected patient death: consolation of the grieved.

OBJECTIVES: To review and assess educational strategies and formats regarding communication with families/survivors in the aftermath of unexpected and untimely patient death. To propose an integrated curriculum designed and intended to foster proficiency, competence, confidence, and composure in relaying catastrophic information in the context of the professional experience of a cohort of seasoned surgeons. BACKGROUND: Unexpected and untimely patient death is emotionally and psychologically wrenching for families, surgeons, and healthcare providers. We have previously proffered that 2 distinct, but interactive, phases of response are relevant when communicating with a family before and after the event: a proactive phase intended to establish a positive therapeutic relationship with the family; and a reactive phase intended to respond to the family in a compassionate and respectful manner and to ensure self-care for the physicians and health care providers. STUDY DESIGN: Survey of a cohort of senior surgeons (membership of the Southern Surgical Association) and Surgical Residency Program Directors (membership of the Association of Program Directors in Surgery). RESULTS: Sixty percent of the senior surgeons surveyed had experienced unexpected patient death. They advised strategies to cope with that clinical situation commensurate with the core competencies of the Accreditation Council for Graduate Medical Education: Medical Knowledge: maximize objective information/data and minimize subjective opinion; Patient Care: critique the events and conduct postmortem analyses; Interpersonal and Communication Skills: honesty, empathy, and patience; Professionalism: provide emotional and psychological support to family and personnel with privacy and in a nonaccusatory manner; Practice-Based Learning and Improvement: preoperative discussion and documentation in the context of informed consent and advanced directives vis-á-vis risk-benefit, effort-yield, and benefit-burden analyses; and Systems-Based Practice: involve chaplains and hospital personnel. Thirty-six percent of the graduate surgical educational programs surveyed allegedly provided educational venues to enable surgical residents to cope with unexpected patient death, although the formats were not specified. CONCLUSIONS: Graduate, postgraduate, and continuing educational programs aspire to prepare physicians and surgeons for independent professional practice-scientifically, humanistically, and artistically. Incorporating educational strategies to enable graduates to cope with the emotional and psychological turmoil of unexpected patient death is relevant.

The temporal relationship between glucose-corrected serum sodium and neurological status in severe diabetic ketoacidosis.

OBJECTIVE: Cerebral oedema is a potentially devastating complication of diabetic ketoacidosis (DKA). The relationship between osmolar changes, acid-base changes and development of cerebral oedema during therapy is unclear. DESIGN: Retrospective cohort study on 53 children with severe DKA (mean pH at presentation 6.92±0.08). Cerebral oedema was diagnosed using neurological status, response to osmotherapy, and neuroimaging, and classified as: early (occurring ≤1 h after presentation, n=15), late (1-48 h, n=17) or absent (controls, n=21). The temporal profiles for various osmolar and acid-base profiles were examined using a random coefficients fractional polynomial mixed model, adjusted for known risk factors. RESULTS: The three groups could not be differentiated by demographic, osmolar or acid-base variables at presentation. All osmolar and acid-base variables showed non-linear temporal trajectories. Children who developed late onset oedema showed dramatically different temporal profiles for effective osmolality and glucose-corrected serum sodium (both p<0.001). Glucose-corrected sodium provided better qualitative discrimination, in that it typically fell in children who developed late oedema and rose in controls. The maximum between-group difference for both variables approximated the median time of clinical cerebral oedema onset. Blood glucose and acid-base temporal profiles did not differ between the groups. Late onset oedema patients received more fluid in the first 4 h, but this did not influence the osmolar or glucose-corrected sodium trajectories in a predictable fashion. CONCLUSIONS: Glucose-corrected serum sodium may prove a useful early warning for the development of cerebral oedema in DKA.

Spirituality within the patient-surgeon relationship.

OBJECTIVE: To assess the attitudes of general and orthopaedic surgical outpatients regarding inquiry into their religious beliefs, spiritual practices, and personal faith. DESIGN: Prospective, voluntary, self-administered, and anonymously-completed questionnaire, regarding religious beliefs, spiritual practices, and personal faith, March-August, 2009. SETTING: General and orthopaedic surgical outpatient settings, Health Services Foundation, College of Medicine, University of South Alabama, a tertiary care academic medical center in Mobile, Alabama. PARTICIPANTS: All patients referred for evaluation and management of general and orthopaedic surgical conditions, pre- and postoperatively, were approached. METHODOLOGY: The questionnaire solicited data regarding patient: (1) demographics; (2) religious beliefs, spiritual practices, and personal faith; and (3) opinions regarding inquiry into those subjects by their surgeon. The latter opinions were stratified on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree." Statistical analysis was conducted using software JMP(®) 8 Statistical Discovery Software (S.A.S. Institute Inc., Cary, North Carolina) and a 5% probability level was used to determine significance of results. RESULTS: Eighty-three percent (83%) of respondents agreed or strongly agreed that surgeons should be aware of their patients' religiosity and spirituality; 63% concurred that surgeons should take a spiritual history; and 64% indicated that their trust in their surgeon would increase if they did so. Nevertheless, 17%, 37%, and 36% disagreed or strongly disagreed with those perspectives, respectively. CONCLUSIONS: By inference to the best explanation of the results, we would argue that religiosity and spirituality are inherent perspectives of patient-surgeon relationships. Consequently, those perspectives are germane to the therapeutic milieu. Therefore, discerning each patient's perspective in those regards is warranted in the context of an integrative and holistic patient-surgeon relationship, the intent of which is to restore a patient to health and well-being.

The quality of reporting and publication status of vaccines trials presented at veterinary conferences from 1988 to 2003.

Conference proceedings, although an importance source to learn about new interventions, are brief and not subject to external evaluation prior to publication. Studies in human medicine suggest that trial results from conference proceedings may be poorly reported. The primary objective of this study was to evaluate characteristics of veterinary vaccine studies published in conference proceedings. 154 cattle or swine vaccine trials presented at veterinary practitioner conferences held in the United States from 1988 to 2003 were the test base to evaluate the following: abstract-to-publication ratio, positive-outcome ratios, differences between proceeding and subsequent journal articles, and compliance with the CONSORT Statement extension for abstracts. The abstract-to-publication ratio was 5/89 for swine trials and 6/65 for cattle trials. The positive-outcome ratio for swine conference proceeding and journal articles was 57/89 and 4/5 respectively. The positive-outcome ratio for bovine conference proceeding and journal articles was 34/65 and 4/6 respectively. No major differences were found between conference proceedings and matching journal articles. Fewer than 10% of conference proceedings included: identification of the trials as randomized in the title, study design as field or challenge; the primary outcome; trial status; results for primary outcome; information about harms and funding source (2/89). When conference proceedings are subsequently published in journals; there is no significant difference in the data, however subsequent publication is uncommon. For many conference proceedings it would be difficult to assess the internal and external validity of the trial based on the information reported.