Understanding and improving the care pathway for children with autism

Purpose: To describe current care pathways for children with autism including enablers and barriers, as experienced by health professionals, education professionals, and families in South Wales, UK. Design/methodology/approach: A mixed-methods approach using focus group discussions, creative writing workshops and visualisation using rich pictures. Findings: The experiences of the care pathways differed significantly across the three groups. Health professionals described the most rigidly-structured pathways, with clear entry points and outcomes. Education professionals and parents described more complex and confusing pathways, with parents assuming the responsibility of coordinating the health and education activity in a bid to link the two independent pathways. All three groups identified enablers, although these differed across the groups. The barriers were more consistent across the groups (e.g. poor communication, missing information, lack of transparency, limited post diagnosis services and access to services based on diagnosis rather than need). Practical implications: This research could inform the design of new services which are premised on multi-agency and multi-disciplinary working to ensure children with ASD receive joined up services and support. Originality/value: Although this study did not represent all professional groups or all experiences of autism, we examined three different perspectives of the ASD pathway. In addition, we triangulated high-level process maps with rich pictures and creative writing exercises, which allowed us to identify specific recommendations to improve integration and reduce duplication and gaps in provision

Oral Hydration Before and After Hip Replacement: The Notion Behind Every Action.

Introduction: Even though nearly 20 patients undergo hip replacement every hour just in Italy and the United Kingdom, it is unclear what are the most appropriate oral hydration practices that patients should follow before and after surgery. Improper administration can cause postoperative fluid disturbances or exacerbate pre-existing conditions, which are not an uncommon find in older subjects. Significance: Considering that the number of hip operations is expected to increase in the next years as well as the age of patients, it is important to recall the notions behind water balance, especially in light of modern surgical and anesthetic practices. This technical perspective discusses the perioperative changes in the hydration status that occur during hip replacement and provides the concepts that help clinicians to better manage how much water the patient can drink. Results: The points of view of the surgeon, the anesthetist, and the nurse are offered together with the description of mineral waters intended for human consumption. Before surgery, water should be always preferred over caffeinated, sugar-sweetened, and alcoholic beverages. The drinking requirements on the day of surgery should consider the water output from urine, feces, respiration, exudation, and bleeding along with the water input from metabolic production and intravenous administration of fluids and medications. Healthy eating habits provide water and should be promoted before and after surgery. Conclusions: The judgment on which is the most appropriate approach to oral hydration practices must be the responsibility of the multidisciplinary perioperative team. Nevertheless, it is reasonable to argue that, in the presence of a patient with no relevant illness and who follows a healthy diet, it is more appropriate to stay closer to dehydration than liberalizing water intake both prior to surgery and in the early postoperative hours until the resumption of normal physiological functions

Using Neural Networks with Routine Health Records to Identify Suicide Risk: Feasibility Study

Background: Each year, approximately 800,000 people die by suicide worldwide, accounting for 1-2 in every 100 deaths. It is always a tragic event with a huge impact on family, friends, the community and health professionals. Unfortunately, suicide prevention and the development of risk assessment tools have been hindered by the complexity of the underlying mechanisms and the dynamic nature of a person's motivation and intent. Many of those who die by suicide had contact with health services in the preceding year but identifying those most at risk remains a challenge. Objective: To explore the feasibility of using artificial neural networks with routinely collected electronic health records to support the identification of those at high risk of suicide when in contact with health services. Methods: Using the Secure Anonymised Information Linkage Databank UK, we extracted the data of those who died by suicide between 2001 and 2015 and paired controls. Looking at primary (general practice) and secondary (hospital admissions) electronic health records, we built a binary feature vector coding the presence of risk factors at different times prior to death. Risk factors included: general practice contact and hospital admission; diagnosis of mental health issues; injury and poisoning; substance misuse; maltreatment; sleep disorders; and the prescription of opiates and psychotropics. Basic artificial neural networks were trained to differentiate between the suicide cases and paired controls. We interpreted the output score as the estimated suicide risk. System performance was assessed with 10x10-fold repeated cross-validation, and its behavior was studied by representing the distribution of estimated risk across the cases and controls, and the distribution of factors across estimated risks. Results: We extracted a total of 2604 suicide cases and 20 paired controls per case. Our best system attained a mean error rate of 26.78% (SD 1.46; 64.57% of sensitivity and 81.86% of specificity). While the distribution of controls was concentrated around estimated risks <0.5, cases were almost uniformly distributed between 0 and 1. Prescription of psychotropics, depression and anxiety, and self-harm increased the estimated risk by similar to 0.4. At least 95% of those presenting these factors were identified as suicide cases. Conclusions: Despite the simplicity of the implemented system, the proposed methodology obtained an accuracy like other published methods based on specialized questionnaire generated data. Most of the errors came from the heterogeneity of patterns shown by suicide cases, some of which were identical to those of the paired controls. Prescription of psychotropics, depression and anxiety, and self-harm were strongly linked with higher estimated risk scores, followed by hospital admission and long-term drug and alcohol misuse. Other risk factors like sleep disorders and maltreatment had more complex effects

Benthic and Hyporheic Macroinvertebrate Distribution Within the Heads and Tails of Riffles During Baseflow Conditions

The distribution of lotic fauna is widely acknowledged to be patchy reflecting the interaction between biotic and abiotic factors. In an in-situ field study, the distribution of benthic and hyporheic invertebrates in the heads (downwelling) and tails (upwelling) of riffles were examined during stable baseflow conditions. Riffle heads were found to contain a greater proportion of interstitial fine sediment than riffle tails. Significant differences in the composition of benthic communities were associated with the amount of fine sediment. Riffle tail habitats supported a greater abundance and diversity of invertebrates sensitive to fine sediment such as EPT taxa. Shredder feeding taxa were more abundant in riffle heads suggesting greater availability of organic matter. In contrast, no significant differences in the hyporheic community were recorded between riffle heads and tails. We hypothesise that clogging of hyporheic interstices with fine sediments may have resulted in the homogenization of the invertebrate community by limiting faunal movement into the hyporheic zone at both the riffle head and tail. The results suggest that vertical hydrological exchange significantly influences the distribution of fine sediment and macroinvertebrate communities at the riffle scale

Characterization of an Nmr Homolog That Modulates GATA Factor-Mediated Nitrogen Metabolite Repression in Cryptococcus neoformans

Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570