Can we screen for pancreatic cancer? Identifying a sub-population of patients at high risk of subsequent diagnosis using machine learning techniques applied to primary care data.

BACKGROUND: Pancreatic cancer (PC) represents a substantial public health burden. Pancreatic cancer patients have very low survival due to the difficulty of identifying cancers early when the tumour is localised to the site of origin and treatable. Recent progress has been made in identifying biomarkers for PC in the blood and urine, but these cannot be used for population-based screening as this would be prohibitively expensive and potentially harmful. METHODS: We conducted a case-control study using prospectively-collected electronic health records from primary care individually-linked to cancer registrations. Our cases were comprised of 1,139 patients, aged 15-99 years, diagnosed with pancreatic cancer between January 1, 2005 and June 30, 2009. Each case was age-, sex- and diagnosis time-matched to four non-pancreatic (cancer patient) controls. Disease and prescription codes for the 24 months prior to diagnosis were used to identify 57 individual symptoms. Using a machine learning approach, we trained a logistic regression model on 75% of the data to predict patients who later developed PC and tested the model's performance on the remaining 25%. RESULTS: We were able to identify 41.3% of patients 60 years were similarly identified at 17 months, with 65% sensitivity, 57% specificity and, 61% AUC. We estimate that combining our algorithm with currently available biomarker tests could result in 30 older and 400 younger patients per cancer being identified as 'potential patients', and the earlier diagnosis of around 60% of tumours. CONCLUSION: After further work this approach could be applied in the primary care setting and has the potential to be used alongside a non-invasive biomarker test to increase earlier diagnosis. This would result in a greater number of patients surviving this devastating disease

Radiomic markers of intracerebral hemorrhage expansion on non-contrast CT: independent validation and comparison with visual markers

Objective: To devise and validate radiomic signatures of impending hematoma expansion (HE) based on admission non-contrast head computed tomography (CT) of patients with intracerebral hemorrhage (ICH). Methods: Utilizing a large multicentric clinical trial dataset of hypertensive patients with spontaneous supratentorial ICH, we developed signatures predictive of HE in a discovery cohort (n = 449) and confirmed their performance in an independent validation cohort (n = 448). In addition to n = 1,130 radiomic features, n = 6 clinical variables associated with HE, n = 8 previously defined visual markers of HE, the BAT score, and combinations thereof served as candidate variable sets for signatures. The area under the receiver operating characteristic curve (AUC) quantified signatures’ performance. Results: A signature combining select radiomic features and clinical variables attained the highest AUC (95% confidence interval) of 0.67 (0.61–0.72) and 0.64 (0.59–0.70) in the discovery and independent validation cohort, respectively, significantly outperforming the clinical (pdiscovery = 0.02, pvalidation = 0.01) and visual signature (pdiscovery = 0.03, pvalidation = 0.01) as well as the BAT score (pdiscovery < 0.001, pvalidation < 0.001). Adding visual markers to radiomic features failed to improve prediction performance. All signatures were significantly (p < 0.001) correlated with functional outcome at 3-months, underlining their prognostic relevance. Conclusion: Radiomic features of ICH on admission non-contrast head CT can predict impending HE with stable generalizability; and combining radiomic with clinical predictors yielded the highest predictive value. By enabling selective anti-expansion treatment of patients at elevated risk of HE in future clinical trials, the proposed markers may increase therapeutic efficacy, and ultimately improve outcomes

The coronal plane maximum diameter of deep intracerebral hemorrhage predicts functional outcome more accurately than hematoma volume

Background: Among prognostic imaging variables, the hematoma volume on admission computed tomography (CT) has long been considered the strongest predictor of outcome and mortality in intracerebral hemorrhage. Aims: To examine whether different features of hematoma shape are associated with functional outcome in deep intracerebral hemorrhage. Methods: We analyzed 790 patients from the ATACH-2 trial, and 14 shape features were quantified. We calculated Spearman’s Rho to assess the correlation between shape features and three-month modified Rankin scale (mRS) score, and the area under the receiver operating characteristic curve (AUC) to quantify the association between shape features and poor outcome defined as mRS>2 as well as mRS > 3. Results: Among 14 shape features, the maximum intracerebral hemorrhage diameter in the coronal plane was the strongest predictor of functional outcome, with a maximum coronal diameter >∼3.5 cm indicating higher three-month mRS scores. The maximum coronal diameter versus hematoma volume yielded a Rho of 0.40 versus 0.35 (p = 0.006), an AUC[mRS>2] of 0.71 versus 0.68 (p = 0.004), and an AUC[mRS>3] of 0.71 versus 0.69 (p = 0.029). In multiple regression analysis adjusted for known outcome predictors, the maximum coronal diameter was independently associated with three-month mRS (p < 0.001). Conclusions: A coronal-plane maximum diameter measurement offers greater prognostic value in deep intracerebral hemorrhage than hematoma volume. This simple shape metric may expedite assessment of admission head CTs, offer a potential biomarker for hematoma size eligibility criteria in clinical trials, and may substitute volume in prognostic intracerebral hemorrhage scoring systems

Hepatic Sarcoidosis Presenting as Portal Hypertension and Liver Cirrhosis: Case Report and Review of the Literature

Systemic sarcoidosis is a disease of unknown etiology, with the liver being the third most commonly affected organ. Most cases of hepatic sarcoidosis are not clinically apparent, but a few can progress to liver cirrhosis, portal hypertension and ultimately liver failure. The diagnosis of hepatic sarcoidosis is difficult, considering that no single laboratory test or radiographic finding can definitively diagnose this systemic disease. Diagnosis of hepatic sarcoidosis relies heavily on histopathologic evaluation of two or more organs, a diagnostic modality that is invasive and may not be applicable to all patients. The treatment of hepatic sarcoidosis is challenging, with no large randomized controlled trials done to date. Physicians must be aware of the complications of hepatic sarcoidosis, and must include the same in the differential diagnosis of liver cirrhosis. We present a case of hepatic sarcoidosis complicated by portal hypertension and liver cirrhosis

Belonging, social connection and non-clinical care: Experiences of HIV peer support among recently diagnosed people living with HIV in Australia

Effective HIV treatments have transformed the medical needs of people living with HIV (PLHIV) to a chronic condition. However, stigma, poorer mental health outcomes and social isolation remain significant challenges for many PLHIV. HIV peer support programs have assisted PLHIV in navigating the clinical, emotional and social aspects of living with HIV. We draw on semi-structured interviews with 26 recently diagnosed PLHIV in Australia to explore experiences of HIV peer support services. Our thematic analysis identified three overarching themes. First, participants commonly reported that peer support programs offered a sense of belonging and connection to a broader HIV community. This established a network, sometimes separate to their existing social networks, of other PLHIV with whom to share experiences of HIV. Second, peer-based programs provided an opportunity for participants to hear firsthand, non-clinical perspectives on living with HIV. While participants valued the clinical care they received, the perspectives of peers gave participants insights into how others had managed aspects of living with HIV such as disclosure, sex and relationships. Finally, participants highlighted important considerations around ensuring referrals were made to socially and culturally appropriate support programs. Peer support programs fill an important gap in HIV care, working alongside and extending the work of the clinical management of HIV. Incorporating formal referrals to peer support services as part of the HIV diagnosis process could assist recently diagnosed PLHIV in adjusting to a positive diagnosis

Different Patterns of Inappropriate Antimicrobial Use in Surgical and Medical Units at a Tertiary Care Hospital in Switzerland: A Prevalence Survey

Audits of individual patient care provide important data to identify local problems in antimicrobial prescription practice. In our study, antimicrobial prescriptions without indication, and divergence from institutional guidelines were frequent errors. Based on these results, we will tailor education, amend institutional guidelines and further develop the infectious diseases consultation service

Dynamics of HEV viremia, fecal shedding and its relationship with transaminases and antibody response in patients with sporadic acute hepatitis E

<p>Abstract</p> <p>Background</p> <p>There is paucity of data regarding duration of fecal excretion and viremia on sequential samples from individual patients and its correlation with serum transaminases and antibody responses in patients with acute hepatitis E. This prospective study was undertaken at a tertiary care center in Northern India over 15 months. Only those patients of sporadic acute hepatitis E who were in their first week of illness and followed up weekly for liver function tests, IgM anti HEV antibody and HEV RNA in sera and stool were included. HEV RNA was done by RT - nPCR using two pairs of primers from RdRp region of ORF 1 of the HEV genome.</p> <p>Results</p> <p>Over a period of 15 months 60 patients met the inclusion criterion and were enrolled for the final analysis. The mean age of the patients was 29.2 ± 8.92 years, there were 39 males. The positivity of IgM anti HEV was 80% at diagnosis and 18.3% at 7th week, HEV RNA 85% at diagnosis and 6.6% at 7th week and fecal RNA 70% at the time of diagnosis and 20% at 4th week. The maximum duration of viremia detected was 42 days and fecal viral shedding was 28 days after the onset of illness.</p> <p>Conclusion</p> <p>Present study reported HEV RNA positivity in sera after normalization of transaminases. Fecal shedding was not seen beyond normalization of transaminases. However, viremia lasted beyond normalization of transaminases suggesting that liver injury is independent of viral replication.</p

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Effectiveness and cost-effectiveness of a patient-initiated botulinum toxin treatment model for blepharospasm and hemifacial spasm: a study protocol for a randomised controlled trial

Background Blepharospasm and hemifacial spasm are debilitating conditions that significantly impact on patient quality of life. Cyclical treatment with botulinum toxin injections offers temporary relief, but the duration of treatment efficacy is variable. The standard model of patient care defines routine fixed-time based scheduled treatment cycles which may lead to unnecessarily frequent treatment for some patients and experience of distressing symptoms in others, if symptoms return before the scheduled follow-up period. Methods/Design A randomised controlled trial will compare a patient-initiated model of care, where patients determine botulinum toxin treatment timing, to the standard model of care in which care is scheduled by the clinical team. A sample of 266 patients with blepharospasm or hemifacial spasm will be recruited from Moorfields Eye Hospital (MEH), London. The trial will be accompanied by a mixed methods evaluation of acceptability of the new service. Patients who meet eligibility criteria will be assessed at baseline and those in the intervention group will be provided instructions on how to book their own treatment appointments. Patients in both groups will be followed up 3 and 9 months into the trial and all patients will be returned to usual care after 9 months to meet safety protocols. Primary outcome measures include disease severity (questionnaire), functional disability (questionnaire) and patient satisfaction with care (questionnaire). Secondary outcomes include disease-specific quality of life (questionnaire), mood (questionnaire), illness and treatment perceptions (questionnaire and semi-structured interviews), economic impact (questionnaire) and acceptability (questionnaire and semi-structured interviews). Discussion This trial will assess the effectiveness and cost-effectiveness of a patient-led care model for botulinum toxin therapy. If the new model is shown to be effective in reducing distress and disability in these populations and is found to be acceptable to patients, whilst being cost-effective, this will have significant implications for service organisation across the NHS. Trial registration UK Clinical Research Network (UKCRN) Portfolio 18660. Clinicaltrials.gov ID NCT102577224 (registered 29th October 2015

Zinc status and its association with the health of adolescents: a review of studies in India

Background: Zinc is important in adolescence because of its role in growth and sexual maturation. Adolescents from developing countries such as India may be at high risk of zinc deficiency because of unwholesome food habits and poor bioavailability of zinc from plant-based diets. Objectives: (1) to study zinc status and its association with profile of other micronutrients, (2) to construct a simple tool in the form of Adolescent Micronutrient Quality Index (AMQI) to assess quality of diets of the girls and (3) to examine the effect of zinc supplement on health of adolescent girls. Methods: Girls (10&#x2013;16 years) from two secondary schools of Pune, Maharashtra state, in Western India were enrolled in a cross-sectional study (n = 630). Data were collected on dietary intake, cognitive performance, taste acuity, haemoglobin, erythrocyte zinc and plasma levels of zinc, vitamin C, &#x03B2;-carotene and retinol. AMQI was developed using age&#x2013;sex-specific Indian dietary guidelines and healthy foods and habits described in the recent US dietary guidelines. Zinc-rich recipes were developed considering habitual diets of the girls and vegetarian sources of zinc. An intervention trial (n = 180) was conducted to assess the effect of zinc-rich dietary supplements and ayurvedic zinc (Jasad) supplementation. Results: Prevalence of micronutrient deficiencies was high in these girls. Poor cognitive performance was seen in half of the girls, and salt taste perception was affected in 45%. AMQI was correlated with nutrient intakes and blood micronutrient levels (p &#60; 0.01), indicating the potential of AMQI to measure micronutrient quality of diets of adolescent girls. Results of the intervention trial indicated that supplementation of zinc-rich recipes vis-a-vis ayurvedic Jasad zinc has the potential to improve plasma zinc status, cognitive performance and taste acuity in adolescent girls. Conclusion: Review of the studies on Indian adolescent girls demonstrates the necessity of adopting zinc and micronutrient-rich diets for positive health building in adolescents