Integrated Care in Neurology: The Current Landscape and Future Directions.

The rising burden of neurological disorders poses significant challenges to healthcare systems worldwide. There has been an increasing momentum to apply integrated approaches to the management of several chronic illnesses in order to address systemic healthcare challenges and improve the quality of care for patients. The aim of this paper is to provide a narrative review of the current landscape of integrated care in neurology. We identified a growing body of research from countries around the world applying a variety of integrated care models to the treatment of common neurological conditions. Based on our findings, we discuss opportunities for further study in this area. Finally, we discuss the future of integrated care in Canada, including unique geographic, historical, and economic considerations, and the role that integrated care may play in addressing challenges we face in our current healthcare system.

Characterization of patients with brain metastases referred to palliative care.

PURPOSE: In this study, we aimed to assess the clinical characteristics, reasons for referral, and outcomes of patients with brain metastases (BM) referred to the supportive care center. METHODS: Equal numbers of patients with melanoma, breast cancer, and lung cancer with (N = 90) and without (N = 90) BM were retrospectively identified from the supportive care database for study. Descriptive statistics were used to analyze demographic, disease, and clinical data. Kaplan Meier method was used to evaluate survival outcomes. RESULTS: While physical symptom management was the most common reason for referral to supportive care for both patients with and without BM, patients with BM had significantly lower pain scores on ESAS at time of referral (p = 0.002). They had greater interaction with acute care in the last weeks of life, with higher rates of ICU admission, emergency room visits, and hospitalizations after initial supportive care (SC) visit. The median survival time from referral to Supportive Care Center (SCC) was 0.90 years (95% CI 0.73, 1.40) for the brain metastasis group and 1.29 years (95% CI 0.91, 2.29) for the group without BM. CONCLUSIONS: Patients with BM have shorter survival and greater interaction with acute care in the last weeks of life. This population also has distinct symptom burdens from patients without BM. Strategies to optimize integration of SC for patients with BM warrant ongoing study.

Cycle Threshold Values as Indication of Increasing SARS-CoV-2 New Variants, England, 2020-2022.

Early detection of increased infections or new variants of SARS-CoV-2 is critical for public health response. To determine whether cycle threshold (Ct) data from PCR tests for SARS-CoV-2 could serve as an early indicator of epidemic growth, we analyzed daily mean Ct values in England, UK, by gene target and used iterative sequential regression to detect break points in mean Ct values (and positive test counts). To monitor the epidemic in England, we continued those analyses in real time. During September 2020-January 2022, a total of 7,611,153 positive SARS-CoV-2 PCR test results with Ct data were reported. Spike (S) gene target (S+/S-)-specific mean Ct values decreased 6-29 days before positive test counts increased, and S-gene Ct values provided early indication of increasing new variants (Delta and Omicron). Our approach was beneficial in the context of the first waves of the COVID-19 pandemic and can be used to support future infectious disease monitoring.

Characterization of industry relationships in oncology.

BACKGROUND: Collaborative relationships between academic oncology and industry (pharmaceutical, biotechnology, "omic," and medical device companies) are essential for therapeutic development in oncology; however, limited research on engagement in and perceptions of these relationships has been done. METHODS: Survey questions were developed to evaluate relationships between academic oncology and industry. An electronic survey was delivered to 1000 randomly selected members of the American Society of Clinical Oncology, a professional organization for oncologists, eliciting respondents' views around oncology-industry collaborations. The responses were analyzed according to prespecified plans. RESULTS: There were 225 survey respondents. Most were from the United States (70.0%), worked at an academic institution (60.1%), worked in medical oncology (81.2%), and had an active relationship with industry (85.8%). One quarter (26.7%) of respondents reported difficulty establishing a relationship with industry collaborators, and most respondents (75%) did not report having had mentorship in developing these relationships. The majority (85.3%) of respondents considered these collaborations important to their careers. Respondents generally thought that scientific integrity was preserved (92%), and most respondents (95%) had little concern over the quality of the collaborative product. Many (60%) shared concerns over potential conflict of interest if an individual with a compensated relationship promoted an industry product for clinical care/research, yet most respondents (67%) stated these relationships did not shape their interactions with patients. CONCLUSIONS: This study provides novel data characterizing the nature of collaborative relationships between clinicians, researchers, and industry in oncology. Although respondents considered these collaborations an important part of clinical and academic oncology, formal education or mentorship around these relationships was rare. Conflicting findings around conflict of interest highlight the importance of more dedicated research in this area. PLAIN LANGUAGE SUMMARY: Business enterprises in health care play a central role in cancer research and care, driving the development of new medical testing, drugs, and devices. Effective working relationships among clinicians, researchers, and these industry partners can promote innovative research and enhance patient care. Study of these collaborations has been limited to date. Through distribution of a questionnaire to cancer clinicians and researchers, we found that most participants consider these relationships valuable, though they find establishing such relationships challenging partly because of gaps in educational programs in this area. Our findings also highlight the need for further policy around the potential bias these relationships can introduce.

The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

Assessing Student Readiness to Work with People Who Use Drugs: Development of a Multi-disciplinary Addiction Educational Survey.

BACKGROUND: As health profession schools implement addiction curricula, they need survey instruments to evaluate the impact of the educational interventions. However, existing measures do not use current non-stigmatizing language and fail to capture core concepts. OBJECTIVE: To develop a brief measure of health profession student readiness to work with people who use drugs (PWUDs) and establish its content validity. METHODS: We conducted a literature review of existing instruments and desired clinical competencies related to providing care to PWUD and used results and expert feedback to create and revise a pool of 72 items. We conducted cognitive interviews with ten pre-clinical health profession students from various US schools of nursing, pharmacy, and medicine to ensure the items were easy to understand. Finally, we used a modified Delphi process with twenty-four health professions educators and addiction experts (eight each from nursing, pharmacy, and medicine) to select items for inclusion in the final scale. We analyzed expert ratings of individual items and interdisciplinary agreement on ratings to decide how to prioritize items. We ultimately selected 12 attitudes and 12 confidence items to include in the REadiness to Discuss Use, Common Effects, and HArm Reduction Measure (REDUCE-HARM). Experts rated their overall assessment of the final scale. RESULTS: Twenty-two of twenty-four experts agreed or strongly agreed that the attitudes scale measures student attitudes that impact readiness to work with PWUDs. Twenty-three of twenty-four experts agreed or strongly agreed that the confidence scale measures student self-efficacy in competencies that impact readiness to work with PWUDs. Seven of 72 initial items and none of the 24 selected items had statistically significant differences between disciplines. CONCLUSIONS: The REDUCE-HARM instrument has strong content validity and may serve as a useful tool in evaluating addiction education. Additional research is needed to establish its reliability, construct validity, and responsiveness to change.

Patient and health-care provider experience of a person-centred, multidisciplinary, psychosocial support and harm reduction programme for patients with harmful use of alcohol and drug-resistant tuberculosis in Minsk, Belarus.

BACKGROUND: Tuberculosis (TB) often concentrates in groups of people with complex health and social issues, including alcohol use disorders (AUD). Risk of TB, and poor TB treatment outcomes, are substantially elevated in people who have AUD. Médecins sans Frontières and the Belarus Ministry of Health have worked to improve treatment adherence in patients with multi-drug or rifampicin resistant (MDR/RR)-TB and harmful use of alcohol. In 2016, a person-centred, multidisciplinary, psychosocial support and harm reduction programme delivered by TB doctors, counsellors, psychiatrists, health-educators, and social workers was initiated. In 2020, we described patient and provider experiences within the programme as part of a wider evaluation. METHODS: We recruited 12 patients and 20 health-care workers, using purposive sampling, for in-depth individual interviews and focus group discussions. We used a participant-led, flexible, exploratory approach, enabling participants and the interviewer to shape topics of conversation. Qualitative data were coded manually and analysed thematically. As part of the analysis process, identified themes were shared with health-care worker participants to enable their reflections to be incorporated into the findings. RESULTS: Key themes related to the patients' and practitioners experience of having and treating MDRTB with associated complex health and social issues were: fragility and despair and guidance, trust and health. Prejudice and marginalisation were global to both themes. Counsellors and other health workers built a trusting relationship with patients, enabling guidance through a multi-disciplinary approach, which supported patients to achieve their vision of health. This guidance was achieved by a team of social workers, counsellors, doctors and health-educators who provided professional and individualised help for patients' illnesses, personal or interpersonal problems, administrative tasks, and job searches. CONCLUSIONS: Patients with MDR/RR-TB and harmful use of alcohol faced complex issues during treatment. Our findings describe how person-centred, multi-disciplinary, psychosocial support helped patients in this setting to cope with these challenges and complete the treatment programme. We recommend that these findings are used to: i) inform programmatic changes to further boost the person-centred care nature of this program; and ii) advocate for this type of person-centred care approach to be rolled out across Belarus, and in contexts that face similar challenges.

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

Neurocognitive Impairment After Hematopoietic Stem Cell Transplant for Hematologic Malignancies: Phenotype and Mechanisms.

Hematopoietic stem cell transplant (HSCT) plays a central role in the treatment of hematologic cancers. With the increasing survival of patients after HSCT, survivorship issues experienced by this population have become an important outcome. Cognitive impairment is an established sequela of HSCT, with studies to date establishing its presence, associated risk factors, and clinical phenotype. There are multiple potential contributors to cognitive impairment after HSCT. Efforts are ongoing to further characterize its clinical phenotype, associated biomarkers, and biologic underpinnings. A fundamental knowledge of post-HSCT cognitive impairment is of value for all clinicians who interface with this population, and further academic efforts are needed to more fully understand the impact of this cancer treatment on brain health. IMPLICATIONS FOR PRACTICE: As survival outcomes after hematopoietic stem cell transplant (HSCT) improve, an awareness of the post-treatment challenges faced by this population has become central to its care. HSCT can have a sustained and broad impact on brain health, causing cognitive dysfunction, fatigue, disturbed mood, and sleep. In affected patients, autonomy, return to work, relationships, and quality of life may all be affected. A fundamental fluency in this area is important for clinicians interfacing with HSCT survivors, facilitating the identification and management of cognitive dysfunction and concurrent symptom clusters, and stimulating interest in these sequelae as areas for future clinical research.

Development of the pupillary light reflex from 9 to 24 months: association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis.

BACKGROUND: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. METHODS: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD ) were calculated for 190 infants. RESULTS: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (ß = -.16, 95% CI = -0.31, -0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative 'catch-up') between 14 and 24 months relative to those with other outcomes (typical: ß = .54, 95% CI = 0.08, 0.99; other: ß = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (ß = .08, 95% CI = 0.01, 0.14) and RRB (ß = .05, 95% CI = 0.004, 0.11) traits. CONCLUSIONS: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.

"It's a secret between us": a qualitative study on children and care-giver experiences of HIV disclosure in Kinshasa, Democratic Republic of Congo.

BACKGROUND: It is estimated that 64,000 children under 15 years of age are living with HIV in the Democratic Republic of Congo (DRC). Non-disclosure - in which the child is not informed about their HIV status - is likely to be associated with poor outcomes during adolescence including increased risk of poor adherence and retention, and treatment failure. Disclosing a child's HIV status to them can be a difficult process for care-givers and children, and in this qualitative study we explored child and care-giver experiences of the process of disclosing, including reasons for delay. METHODS: A total of 22 in-depth interviews with care-givers and 11 in-depth interviews with HIV positive children whom they were caring for were conducted in one health-care facility in the capital city of Kinshasa. Care-givers were purposively sampled to include those who had disclosed to their children and those who had not. Care-givers included biological parents, grandmothers, siblings and community members and 86% of them were female. Interviews were conducted in French and Lingala. All interviews were translated and/or transcribed into French before being manually coded. Thematic analysis was conducted. Verbal informed consent/assent was taken from all interviewees. RESULTS: At the time of interview, the mean age of children and care-givers was 17 (15-19) and 47 (21-70) years old, respectively. Many care-givers had lost family members due to HIV and several were HIV positive themselves. Reasons for non-disclosure included fear of stigmatisation; wanting to protect the child and not having enough knowledge about HIV or the status of the child to disclose. Several children had multiple care-givers, which also delayed disclosure, as responsibility for the child was shared. In addition, some care-givers were struggling to accept their own HIV status and did not want their child to blame them for their own positive status by disclosing to them. CONCLUSIONS: Child disclosure is a complex process for care-givers, health-care workers and the children themselves. Care-givers may require additional psycho-social support to manage disclosure. Involving multiple care-givers in the care of HIV positive children could offer additional support for disclosure.

Patterns of care for pediatric patients with newly-diagnosed grade II gliomas.

PURPOSE: We describe large-scale demographic, initial treatment, and outcomes data for pediatric grade II gliomas included in the National Cancer Database from 2004 to 2014. METHODS: Our cohort included cases less than 21 years of age with pathology-confirmed disease. Logistic regressions were used to evaluate the use of chemotherapy (CT) and radiation therapy (RT). Overall survival (OS) rates were determined using Kaplan-Meier estimates and the log-rank test. RESULTS: We identified 803 cases with astrocytoma (56.2%), oligodendroglioma (26.0%), and mixed glioma/glioma NOS (17.8%) histologies. Most cases underwent surgical resection (n = 661). Whereas cases 16 to 21 years of age were more likely than cases 0 to 5 years to receive RT (OR = 7.38, 95% CI 3.58-15.21, p < 0.001), they were less likely to receive CT (OR = 0.34, 95% CI 0.22-0.52, p < 0.001). The 5-year OS rates for all cases, cases that underwent surgical resection, and cases managed with biopsy were 87.5%, 92.7%, and 63.6%, respectively. CONCLUSION: In one of the largest series of pediatric grade II gliomas, astrocytoma was the most common histology. Patterns of care and OS outcomes were similar to grade I gliomas, with surgical resection being the most common initial treatment and associated with a favorable rate of OS. Younger patients were more likely to receive post-operative CT and the use of RT increased with age.

Neurologic Toxicities of Immunotherapy.

Immunotherapy has revolutionized treatment of cancer over the past two decades. The antitumor effects of immunotherapy approaches are at the expense of growing spectrum of immune-related adverse events (irAEs) due to cross-reactivity between the tumor and normal host tissue. These adverse events can happen in any organ and range from mild to severe and even life-threatening conditions. While neurological irAEs associated with immune checkpoint inhibitors (CPIs) are rare, they pose a significant challenge in management as the clinical phenotypes are heterogenous and frequently necessitate cessation of therapy and systemic immune suppression and lead to transient functional decline. On the other hand, immune effector cell-associated neurotoxicity (ICANS) is common, frequently occurs in conjunction with cytokine release syndrome (CRS), and poses a significant clinical challenge to the development and widespread use of these effective therapies. Early recognition of these neurological syndromes, timely diagnosis, and thoughtful management are key for further clinical development of these effective therapies in cancer patients. Here, we describe clinical phenotypes of CPI-induced neurological complications and ICANS and discuss steps in clinical monitoring, diagnosis, and effective management.

Personal Agency and Community Resilience: Narratives of Women Navigating Health Care With Chronic Lyme Disease.

Chronic Lyme disease can manifest as a debilitating illness with symptoms that change over time. With its varied presentation, timeline variation, diagnostic difficulty, and lack of definitive treatment, clinical recognition of chronic Lyme disease remains controversial. At the same time, patients face challenges in finding a provider who is supportive and knowledgeable about diagnosing and treating Lyme. We examined the ways the medical system may have affected the lived experiences of chronic Lyme patients. In this article, we communicate the personal, health care, and community illness experiences of 14 women navigating the medical system with chronic Lyme disease through a qualitative community-based participatory research study using interviews and narrative reflection in a rural community setting. The women were interviewed by a researcher living with chronic Lyme disease and the transcripts were analyzed for themes. All participants described navigating multiple allopathic and nonallopathic care modalities to find satisfactory care. They struggled with physical and emotional burdens of chronic, nonlinear illness, as well as disbelief and discrimination by medical providers. Their lives followed patterns of illness and wellness, trust and mistrust of medical treatment, and community connection and disengagement. They learned to become their own advocates to seek affirmative care. They are aware of the controversial nature of their illness, and many have channeled their frustrations into caring for one another through their Lyme community. Women living with controversial diagnoses like chronic Lyme disease experience increased challenges navigating the medical system to find satisfactory care and thus create communities with each other for mutual aid and support. In understanding these challenges, the medical community can improve care for people living with contested chronic illnesses.

Peptide Isolation via Spray Drying: Particle Formation, Process Design and Implementation for the Production of Spray Dried Glucagon.

PURPOSE: Spray drying plays an important role in the pharmaceutical industry for product development of sensitive bio-pharmaceutical formulations. Process design, implementation and optimisation require in-depth knowledge of process-product interactions. Here, an integrated approach for the rapid, early-stage spray drying process development of trehalose and glucagon on lab-scale is presented. METHODS: Single droplet drying experiments were used to investigate the particle formation process. Process implementation was supported using in-line process analytical technology within a data acquisition framework recording temperature, humidity, pressure and feed rate. During process implementation, off-line product characterisation provided additional information on key product properties related to residual moisture, solid state structure, particle size/morphology and peptide fibrillation/degradation. RESULTS: A psychrometric process model allowed the identification of feasible operating conditions for spray drying trehalose, achieving high yields of up to 84.67%, and significantly reduced levels of residual moisture and particle agglomeration compared to product obtained during non-optimal drying. The process was further translated to produce powders of glucagon and glucagon-trehalose formulations with yields of >83.24%. Extensive peptide aggregation or degradation was not observed. CONCLUSIONS: The presented data-driven process development concept can be applied to address future isolation problems on lab-scale and facilitate a systematic implementation of spray drying for the manufacturing of sensitive bio-pharmaceutical formulations.

Neurologic Toxicities of Cancer Immunotherapies: a Review.

PURPOSE OF REVIEW: This review provides clinical characterization and approach to management of neurotoxicities associated with checkpoint inhibitor therapy and chimeric antigen receptor T cell (CAR T cell) therapy. RECENT FINDINGS: Immuno-oncology has revolutionized cancer treatment. The immunomodulatory effect of these treatments extends beyond the targeted cancers; however, with a range of immune-mediated toxicities being associated with these therapies. Both the peripheral and central nervous system are vulnerable to these toxicities, with several distinct clinical syndromes strongly associated with specific immunotherapies. Neurologic immune-related adverse events are significant sequelae of both checkpoint inhibitors and CAR T cell therapy. In addition to clinical characterization of these syndromes, an understanding of the biologic underpinnings of these sequelae is essential. This will facilitate identification of patients at risk of these toxicities, develop treatments to prevent them and identify more effective clinical treatment when they occur.

Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer.

Being able to predict who will likely experience cancer related cognitive impairment (CRCI) could enhance patient care and potentially reduce economic and human costs associated with this adverse event. We aimed to determine if post-treatment patient reported CRCI could also be predicted from baseline resting state fMRI in patients with breast cancer. 76 newly diagnosed patients (n = 42 planned for chemotherapy; n = 34 not planned for chemotherapy) and 50 healthy female controls were assessed at 3 times points [T1 (prior to treatment); T2 (1 month post chemotherapy); T3 (1 year after T2)], and at yoked intervals for controls. Data collection included self-reported executive dysfunction, memory function, and psychological distress and resting state fMRI data converted to connectome matrices for each participant. Statistical analyses included linear mixed modeling, independent t tests, and connectome-based predictive modeling (CPM). Executive dysfunction increased over time in the chemotherapy group and was stable in the other two groups (p < 0.001). Memory function decreased over time in both patient groups compared to controls (p < 0.001). CPM models successfully predicted executive dysfunction and memory function scores (r > 0.31, p < 0.002). Support vector regression with a radial basis function (SVR RBF) showed the highest performance for executive dysfunction and memory function (r = 0.68; r = 0.44, p's < 0.001). Baseline neuroimaging may be useful for predicting patient reported cognitive outcomes which could assist in identifying patients in need of surveillance and/or early intervention for treatment-related cognitive effects.

What can we learn from the last 20 years: A review of litigation trends in otolaryngology.

INTRODUCTION: Litigation in healthcare is a large financial burden to the NHS and can be a cause of great stress to clinicians. The overall number of claims across specialities, from the years 1995-2017 have increased. Despite being one of the smaller surgical specialities, litigation costs are still significant within Otolaryngology. In this piece we sought to analyse the available data to identify trends within litigation and therefore which areas of practise could be improved. METHODS: A freedom of information request was submitted to NHS Resolution for summarised data on claims coded under 'Otolaryngology' or 'ENT' between 1996 and 2017. Information was collected on the total number of claims, the number of successful claims and details on the reasons for making claims. RESULTS: The total number of claims made against Otolaryngology departments from 1996/97 to 2016/17 was 1952. The overall number of claims have increased during this time period. The total amount of money paid out between 1996 and 2017 was £108, 240, 323. The top causes of claim by injury were unnecessary pain and unnecessary operations. The highest number of claims by cause were for failure or delay in diagnosis and intraoperative problems. CONCLUSION: These results highlight areas that local units can focus on to reduce their litigation burden. Targeted initiatives aimed at improving patient-clinician communication, the consent process and improving local organisational efficiency will address a significant proportion of claims. Re-examination of this data on a regular basis can serve as a useful adjunct in assessing the impact of quality improvement initiatives and implementation of best practiseswithin the speciality.

Surgical Emphysema in a Pediatric Tertiary Referral Center.

BACKGROUND: Laryngeal trauma in pediatrics is extremely rare; however, because of the smaller pediatric larynx, it can have catastrophic consequences. Following laryngeal trauma, surgical emphysema is a relatively common presentation. In pediatrics, it can be a life-threatening condition. Here we describe 2 cases of laryngeal trauma resulting in extensive surgical emphysema. CASES: The first case described involves bilateral pneumothoraces, airway compromise, and respiratory arrest and was managed with bilateral chest drains, intubation, and tracheostomy. The second case resulted in widespread surgical emphysema in a stable patient and was managed conservatively. Both cases were monitored closely for a period of time to ensure there were no further sequelae. DISCUSSION: Patients with laryngeal trauma resulting in surgical emphysema have the potential to deteriorate rapidly. Furthermore, surgical emphysema degrades the quality of ultrasound images, which may delay the diagnosis. If there are any concerns about the safety of the airway, then it should be secured definitively with either endotracheal intubation or emergency tracheostomy depending on clinical judgment. It is acceptable to monitor patients closely in a high-dependency unit setting if they are stable and do not show any evidence of laryngeal edema. CONCLUSIONS: We present 2 cases of laryngeal trauma that were dealt with effectively so that both patients made a full recovery. It is important to act quickly to secure the airway if there are any concerns about its patency. Stable patients with no evidence of laryngeal edema can be managed conservatively. Close monitoring is essential to prevent any potential airway compromise.

Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial.

BACKGROUND: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus. METHODS: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77. FINDINGS: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events. INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus. FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.