Implementation of a Maternal Child Knowledgebase.

To advance the application of clinical data to address maternal health we developed and implemented a Maternal Child Knowledgebase (MCK). The MCK integrates data from every pregnancy that received care at the University of Iowa Hospitals & Clinics (UIHC) and links information from the pregnancy episode to the delivery episode and between the mother and child. This knowledgebase contains integrated information regarding diagnoses, medications, mother and child vitals, hospital admissions, depression screenings, laboratory value results, and procedure information. It also collates information from the electronic health record (EPIC), the Social Security Death Index, and the Medication Administration Record into one knowledgebase. To enhance usability, we designed a custom viewer with several pre-designed queries and reports that eliminates the need for users to be proficient in SQL coding. The recent implementation of the MCK has supported multiple projects and reduced the number of Obstetrics-related data queries to the Biomedical Informatics group.

Cancer Trial Impact: Understanding Implementation of the Short Course Oncology Treatment (SCOT) Trial Findings in colorectal cancer at a National Level.

AIMS: The Short Course Oncology Treatment (SCOT) trial indicated that 3 months of adjuvant doublet chemotherapy was non-inferior to 6 months of treatment for patients with colorectal cancer, with considerably less toxicity. The SCOT trial results were disseminated in June 2017. The aim of this study was to understand if SCOT trial findings were implemented in Scotland. MATERIALS AND METHODS: A retrospective analysis was carried out on a dataset derived from a source population of 5.4 million people. Eligible patients were those with stage II or III colorectal cancer who received adjuvant chemotherapy. Logistic regression was applied to understand the extent of practice change to a 3-month adjuvant chemotherapy duration after the SCOT trial results were disseminated. Interrupted time series analysis was used to visualise differences in prescribing trends before and after June 2017 for the overall cohort, and by SCOT trial eligibility. RESULTS: In total, 2310 patients were included in the study; 1957 and 353 treated pre- and post-June 2017, respectively. The median treatment duration decreased from 21 weeks (interquartile range 14-24) prior to June 2017 to 12 weeks (interquartile range 12-21 weeks) after June 2017 (P < 0.001). The proportion of patients receiving over 3 months of adjuvant treatment decreased from 75% to 42% (P < 0.001). This change was most noticeable for patients who met the SCOT trial eligibility criteria, and specifically for those with low-risk stage III disease and those treated with capecitabine and oxaliplatin (CAPOX). Although practice change occurred in all locations, there were differences between regions that could be explained by pre-SCOT trial prescribing trends. DISCUSSION: A significant change in chemotherapy prescribing occurred after dissemination of the SCOT trial results. National, real-world data can be used to capture the extent of implementation of clinical trial results. In this case, implementation was aligned with clinical trial subgroup findings. This type of analysis could be conducted to evaluate the impact of other clinical trials.

Chatbots to Support Mental Wellbeing of People Living in Rural Areas: Can User Groups Contribute to Co-design?

Digital technologies such as chatbots can be used in the field of mental health. In particular, chatbots can be used to support citizens living in sparsely populated areas who face problems such as poor access to mental health services, lack of 24/7 support, barriers to engagement, lack of age appropriate support and reductions in health budgets. The aim of this study was to establish if user groups can design content for a chatbot to support the mental wellbeing of individuals in rural areas. University students and staff, mental health professionals and mental health service users (N = 78 total) were recruited to workshops across Northern Ireland, Ireland, Scotland, Finland and Sweden. The findings revealed that participants wanted a positive chatbot that was able to listen, support, inform and build a rapport with users. Gamification could be used within the chatbot to increase user engagement and retention. Content within the chatbot could include validated mental health scales and appropriate response triggers, such as signposting to external resources should the user disclose potentially harmful information or suicidal intent. Overall, the workshop participants identified user needs which can be transformed into chatbot requirements. Responsible design of mental healthcare chatbots should consider what users want or need, but also what chatbot features artificial intelligence can competently facilitate and which features mental health professionals would endorse.

Maldevelopment of the cranio-facial-respiratory complex: A Darwinian perspective.

AIM: The mammalian Cranio-Facial-Respiratory Complex (CFRC) comprises several different biological tissues that collectively function under coordination from the central nervous and cardiorespiratory systems, primarily to breathe, eat and drink as well as integrating the sensory and motor systems for speech, communication and protective mechanisms. Anthropologists have long recognised that lifelong exposure to modern feeding regimens of readily available and highly processed foods, changes in breastfeeding and weaning, can impact expression of various phenotypic traits affecting the CFRC quite differently than does lifelong exposure to more traditional ancestral feeding regimens, typical of hunter-gather/foraging in non-Western-exposed cultures. The aim of this study is to highlight the role of the paediatric dentist in a multidisciplinary approach in which professionals working in and around the CFRC can actively prevent tooth decay and skeletal-dental malocclusion in the light of evolutionary oral medicine. RESULTS: As a result of changes in the environment, in the food quality, in eating and feeding practices starting from day one, two oral diseases of civilisation, tooth decay and skeletal-dental malocclusion, have both relatively recently reached worldwide epidemic proportions and afflict people of all ages. CONCLUSION: A multidisciplinary approach in which professionals working in and around the CFRC can actively promote prevention or reversal of dento-skeletal and myofunctional disorders, diagnose them when present and coordinate the appropriate therapy and life long maintenance programme.

Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences.

The hippocampus is essential for spatial and episodic memory but is damaged early in Alzheimer's disease and is very sensitive to hypoxia. Understanding how it regulates its oxygen supply is therefore key for designing interventions to preserve its function. However, studies of neurovascular function in the hippocampus in vivo have been limited by its relative inaccessibility. Here we compared hippocampal and visual cortical neurovascular function in awake mice, using two photon imaging of individual neurons and vessels and measures of regional blood flow and haemoglobin oxygenation. We show that blood flow, blood oxygenation and neurovascular coupling were decreased in the hippocampus compared to neocortex, because of differences in both the vascular network and pericyte and endothelial cell function. Modelling oxygen diffusion indicates that these features of the hippocampal vasculature may restrict oxygen availability and could explain its sensitivity to damage during neurological conditions, including Alzheimer's disease, where the brain's energy supply is decreased.

Myofunctional therapy. Part 1: Culture, industrialisation and the shrinking human face.

Culture, industrialisation and the shrinking human face: Why is it important? Over the past 300,000 years, not only has the way we consume food from birth through our lifetime changed, there have also been changes related to the methods of food preparation, availability, processing, and storage. These diet-related factors, along with other epigenetic factors, have led to a widespread increase in orofacial myofunctional disorders (OMDs) and resultant human malocclusion phenotypes (HMPs) worldwide. Currently there is an increasing need for resolution of HMPs in early childhood and associated OMDs. This review will include reports of cases and describe the nature of the problem and strategies for effective solutions.

The key challenges of discussing end-of-life stroke care with patients and families: a mixed-methods electronic survey of hospital and community healthcare professionals.

BACKGROUND: Communication between professionals, patients and families about palliative and end-of-life care after stroke is complex and there is a need for educational resources in this area. METHODS: To explore the key learning needs of healthcare professionals, a multidisciplinary, expert group developed a short electronic survey with open and closed questions, and then distributed it to six UK multiprofessional networks and two groups of local clinicians. RESULTS: A total of 599 healthcare professionals responded. Educational topics that were either definitely or probably needed were: ensuring consistent messages to families and patients (88%); resolving conflicts among family members (83%); handling unrealistic expectations (88%); involving families in discussions without them feeling responsible for decisions (82%); discussion of prognostic uncertainties (79%); likely mode of death (72%); and oral feeding for 'comfort' in patients at risk of aspiration (71%). The free-text responses (n = 489) and 82 'memorable' cases identified similar themes. CONCLUSION: Key topics of unmet need for education in end-of-life care in stroke have been identified and these have influenced the content of an open access, web-based educational resource.

Preliminary validation of a self-efficacy scale for pediatric chronic illness.

BACKGROUND: Tracking self-efficacy may be useful for identifying children at risk for medical noncompliance. We created the Pediatric Rating of Chronic Illness Self-Efficacy (PRCISE) to measure self-efficacy in youth dealing with a chronic illness. METHOD: Data were collected from 217 families where one child aged 7-20 (Mage  = 13.62, SDage  = 2.92; 62.7% Latino, 58.1% female) had a chronic illness. Parent participants provided demographic information. Youth completed a depression measure, the Patient Health Questionnaire for Adolescents and the PRCISE. To determine the underlying latent structure of the scale, an exploratory factor analysis was conducted using parallel analysis. We also carried out two multiple linear regressions to explore the data and establish preliminary predictive validity. RESULTS: The measure was reduced to 15 items, demonstrating a one-factor solution with strong reliability. Predictors of lower self-efficacy included having parents who had not attended college, being African American, and having higher Patient Health Questionnaire for Adolescents scores, R2  = .23, F(11, 174) = 5.62, p < .001. Main effects were qualified by a two-way interaction, such that the decrease in PRCISE scores associated with depressive symptoms was attenuated in children with less educated parents. In terms of predictive validity, higher PRCISE scores unexpectedly predicted more number of emergency room visits, R2  = .12, F(9, 113) = 2.73, p < .01. CONCLUSIONS: The PRCISE appears to be a reliable measure of a single self-efficacy construct. Secondary analyses revealed important health disparities in pediatric chronic illness self-efficacy. Next steps may include validation of the PRCISE using confirmatory factor analysis.

Defective replication stress response inhibits lymphomagenesis and impairs lymphocyte reconstitution.

DNA replication stress promotes genome instability in cancer. However, the contribution of the replication stress response to the development of malignancies remains unresolved. The DNA replication stress response protein SMARCAL1 stabilizes DNA replication forks and prevents replication fork collapse, a cause of DNA breaks and apoptosis. While the fork regression/remodeling functions of SMARCAL1 have been investigated, its in vivo functions in replication stress and cancer are unclear. Using a gamma radiation (IR)-induced replication stress T-cell lymphoma mouse model, we observed a significant inhibition of lymphomagenesis in mice lacking one or both alleles of Smarcal1. Notably, a quarter of the Smarcal1-deficient mice did not develop tumors. Moreover, hematopoietic stem/progenitor cells (HSPCs) and developing thymocytes in Smarcal1-deficient mice showed increased DNA damage and apoptosis during the proliferation burst following IR and an impaired ability to repopulate the thymus after IR. Additionally, mice lacking Smarcal1 showed significant HSPC defects when challenged to respond to other replication stress stimuli. Thus, our data reveal the critical function of the DNA replication stress response and, specifically, Smarcal1 in hematopoietic cell survival and tumor development. Our results also provide important insight into the immunodeficiency observed in individuals with mutations in SMARCAL1 by suggesting that it is an HSPC defect.

Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial.

We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2-26.4%), compared with 6.5% (95% CI 0.2-12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.

Diagnosis and outcome of childhood perineurioma.

INTRODUCTION: Intraneural perineurioma is a rare peripheral nerve tumor of childhood and early adulthood. Patients demonstrate progressive muscle weakness and atrophy largely without sensory complaints. CASE: We report two children with perineurioma affecting the radial and femoral nerves. Electromyography (EMG), ultrasound, and 3-T MR imaging were important tools for localizing perineurioma and permitting its differentiation from other nerve lesions. The first patient underwent surgical excision of the perineurioma and a traditional nerve graft. At 10 months post-operative follow-up, she demonstrated no meaningful recovery of muscle strength compared to her pre-operative assessment. EMG did confirm axonal continuity indicating that reinnervation had occurred via the nerve graft. The second patient underwent a two-staged surgical procedure that included an end-to-side nerve transfer. At 18 months post-operative follow-up, she demonstrated mild improvement in muscle strength and EMG evidence of ongoing reinnervation. CONCLUSION: The surgical management of perineurioma remains controversial, and reports of clinical recovery after nerve grafts and nerve transfers vary. Nerve transfers have been reported to provide superior results to traditional nerve grafting in adults with post-traumatic plexus injuries. The modest gain in strength of our patient who underwent a nerve transfer raises the question if this may also apply to patients with perineurioma. Additional studies will be required, which must also take into consideration that features of long-standing neuropathy (i.e., limb length discrepancy) have the potential to reduce the likelihood of reinnervation and clinical recovery.

A phase II study of capecitabine and oxaliplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract.

BACKGROUND: Advanced biliary tract carcinomas are associated with a poor prognosis, and palliative chemotherapy has only modest benefit. This multi-centre phase II study was conducted to determine the efficacy of capecitabine in combination with oxaliplatin in patients with inoperable gall bladder or biliary tract cancer. METHODS: This was a Phase II, non-randomised, two-stage Simon design, multi-centre study. Ethics approval was sought and obtained by the North West MREC, and then locally by the West Glasgow Hospitals Research Ethics Committee. Eligible patients with inoperable locally advanced or metastatic adenocarcinoma of the gall bladder or biliary tract and with adequate performance status, haematologic, renal, and hepatic function were treated with capecitabine (1000 mg/m(2) po, twice daily, days 1-14) and oxaliplatin (130 mg/m(2) i.v., day 1) every 3 weeks for up to six cycles. The primary objective of the study was to determine the objective tumour response rates (complete and partial). The secondary objectives included assessment of toxicity, progression-free survival, and overall survival. RESULTS: Forty-three patients were recruited between July 2003 and December 2005. The regimen was well tolerated with no grade 3/4 neutropenia or thrombocytopenia. Grade 3/4 sensory neuropathy was observed in six patients. Two-thirds of patients received their chemotherapy without any dose delays. Overall response rate was 23.8% (95% CI 12.05-39.5%). Stable disease was observed in a further 13 patients (31%) and progressive disease observed in 12 (28.6%) of patients. The median progression-free survival was 4.6 months (95% CI 2.8-6.4 months; Fig. 1) and the median overall survival 7.9 months (95% CI 5.3-10.4 months; Fig. 2). Fig. 1 Progression-free survival Fig. 2 Overall survival CONCLUSION: Capecitabine combined with oxaliplatin has a lower disease control and shorter overall survival than the combination of cisplatin with gemcitabine which has subsequently become the standard of care in this disease. However, capecitabine in combination with oxaliplatin does have modest activity in this disease, and can be considered as an alternative treatment option for patients in whom cisplatin and/or gemcitabine are contra-indicated.

Socioeconomic status, human papillomavirus, and overall survival in head and neck squamous cell carcinomas in Toronto, Canada.

BACKGROUND: Despite universal healthcare in some countries, lower socioeconomic status (SES) has been associated with worse cancer survival. The influence of SES on head and neck cancer (HNC) survival is of immense interest, since SES is associated with the risk and prognostic factors associated with this disease. PATIENTS AND METHODS: Newly diagnosed HNC patients from 2003 to 2010 (n=2124) were identified at Toronto's Princess Margaret Cancer Centre. Principal component analysis was used to calculate a composite score using neighbourhood-level SES variables obtained from the 2006 Canada Census. Associations of SES with overall survival were evaluated in HNC subsets and by p16 status (surrogate for human papillomavirus). RESULTS: SES score was higher for oral cavity (n=423) and p16-positive oropharyngeal cancer (OPC, n=404) patients compared with other disease sites. Lower SES was associated with worse survival [HR 1.14 (1.06-1.22), p=0.0002], larger tumor staging (p<0.001), current smoking (p<0.0001), heavier alcohol consumption (p<0.0001), and greater comorbidity (p<0.0002), but not with treatment regimen (p>0.20). After adjusting for age, sex, and stage, the lowest SES quintile was associated with the worst survival only for OPC patients [HR 1.66 (1.09-2.53), n=832], primarily in the p16-negative subset [HR 1.63 (0.96-2.79)]. The predictive ability of the prognostic models improved when smoking/alcohol was added to the model (c-index 0.71 vs. 0.69), but addition of SES did not (c-index 0.69). CONCLUSION: SES was associated with survival, but this effect was lost after accounting for other factors (age, sex, TNM stage, smoking/alcohol). Lower SES was associated with greater smoking, alcohol consumption, comorbidity, and stage.