What proportion of adult allergy referrals to secondary care could be dealt with in primary care by a GP with special interest?

Background: The concept of a General Practitioner with Special Interest (GPwSI) was first proposed in the 2000 National Health Service Plan, as a way of providing specialised treatment closer to the patient’s home and reducing hospital waiting times. Given the patchy and inadequate provision of allergy services in the UK the introduction of GPwSIs might reduce the pressure on existing specialist services. Objectives: This study assessed what proportion of referrals to a specialist allergy clinic could be managed in a GPwSI allergy service with a predefined range of facilities and expertise (accurate diagnosis and management of allergy; skin prick testing; provision of advice on allergen avoidance; ability to assess suitability for desensitisation). Methods: 100 consecutive GP referrals to a hospital allergy clinic were reviewed to determine whether patients could be seen in a community-based clinic led by a general practitioner with special interest (GPwSI) allergy. The documentation relating to each referral was independently assessed by three allergy specialists. The referrals were judged initially on the referral letter alone and then re-assessed with the benefit of information summarised in the clinic letter, to determine whether appropriate triage decisions could be made prospectively. The proportion of referrals suitable for a GPwSI was calculated and their referral characteristics identified. Results: 29 % referrals were judged unanimously appropriate for management by a GPwSI and an additional 30 % by 2 of the 3 reviewers. 18 % referrals were unsuitable for a GPwSI service because of the complexity of the presenting problem, patient co-morbidity or the need for specialist knowledge or facilities. Conclusions and clinical relevance: At least a quarter, and possibly half, of allergy referrals to our hospital-based service could be dealt with in a GPwSI clinic, thereby diversifying the patient pathway, allowing specialist services to focus on more complex cases and reducing the waiting time for first appointments

Environmental bone disease of hitherto undescribed type

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Malacoplakia : case report in tongue and review of the literature

Malakoplakia is a relatively uncommon chronic inflammatory reaction of unknown etiology. It usually affects the genitourinary tract but may rarely involve the tongue. There are many theories that explain this reaction but it seems to be the answer to an infectious agent in a patient with immunologic deficiency. Microscopically, malakoplakia is characterized by the presence of foamy histiocytes with distinctive basophilic inclusions, which are known as MichaelisGutmann bodies due to a partially ingested bacteria and their posterior calcification. There are many alternatives to treat this entity. We report the only case diagnosed in the tongue, in a 15 years-old male in the Maxillofacial Surgery and Stomatology Service of the Hospital San Vicente de Paúl in Medellín, Antioquia, Colombia

Ultra-processed food consumption and risk of obesity: a prospective cohort study of UK Biobank

Objective: To examine the associations between ultra-processed food consumption and risk of obesity among UK adults. Methods: Participants aged 40-69 years at recruitment in the UK Biobank (2006-2019) with dietary intakes collected using 24-hour recall and repeated measures of adiposity - body mass index (BMI), waist circumference (WC) and percentage of body fat (% BF) - were included (N=22,659; median follow-up: 5 years). Ultra-processed foods were identified using the NOVA classification and their consumption was expressed as a percentage of total energy intake. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HR) of several indicators of obesity according to ultra-processed food consumption. Models were adjusted for sociodemographic and lifestyle characteristics. Results: 947 incident cases of overall obesity (BMI≥30 kg/m2) and 1,900 incident cases of abdominal obesity (men: WC≥102cm, women: WC≥88cm) were identified during follow-up. Participants in the highest quartile of ultra-processed food consumption had significantly higher risk of developing overall obesity (HR: 1.79; 95%CI: 1.06─3.03) and abdominal obesity (HR: 1.30; 95%CI: 1.14─1.48). They had higher risk of experiencing a ≥5% increase in BMI (HR: 1.31; 95%CI: 1.20─1.43), WC (HR: 1.35; 95%CI: 1.25─1.45) and %BF (HR: 1.14; 95%CI: 1.03─1.25), than those in the lowest quartile of consumption. Conclusions: Our findings provide evidence that higher consumption of ultra-processed food is strongly associated with a higher risk of multiple indicators of obesity in the UK adult population. Policy makers should consider actions that promote consumption of fresh or minimally processed foods and reduce consumption of ultra-processed foods

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease

Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank

In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 $\beta$-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the $\beta$-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn$^{143}$, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 200

Developing a New Definition and Assessing New Clinical Criteria for Septic Shock For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

IMPORTANCE: Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE: To develop a new definition and clinical criteria for identifying septic shock in adults. DESIGN, SETTING AND PARTICIPANTS: The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28 150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1 309 025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1 847 165) electronic health record (EHR) data sets. MAIN OUTCOMES AND MEASURES: Evidence for and agreement on septic shock definitions and criteria. RESULTS: The systematic review identified 44 studies reporting septic shock outcomes (total of 166 479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock–associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets. CONCLUSIONS AND RELEVANCE: Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation

Semantic aware Bayesian network model for actionable knowledge discovery in linked data

The majority of the conventional mining algorithms treat the mining process as an isolated data-driven procedure and overlook the semantic of the targeted data. As a result, the generated patterns are abundant and end users cannot act upon them seamlessly. Furthermore, interdisciplinary knowledge can not be obtained from domain-specific silo of data. The emergence of Linked Data (LD) as a new model for knowledge representation, which intertwines data with its semantics, has introduced new opportunities for data miners. Accordingly, this paper proposes an ontology-based Semantic-Aware Bayesian network (BN) model. In contrast to the existing mining algorithms, the proposed model does into transform the original format of the LD set. Therefore, it not only accommodates the semantic aspects in LD, but also caters to the need of connecting different data-sets from different domains. We evaluate the proposed model on a Bone Dysplasia dataset, Experimental results show promising performance

Ultra-processed food consumption and obesity in the Australian adult population

Background: Rapid simultaneous increases in ultra-processed food sales and obesity prevalence have been observed worldwide, including in Australia. Consumption of ultra-processed foods by the Australian population was previously shown to be systematically associated with increased risk of intakes of nutrients outside levels recommended for the prevention of obesity. This study aims to explore the association between ultra-processed food consumption and obesity among the Australian adult population and stratifying by age group, sex and physical activity level. Methods: A cross-sectional analysis of anthropometric and dietary data from 7411 Australians aged &ge;20 years from the National Nutrition and Physical Activity Survey 2011&ndash;2012 was performed. Food consumption was evaluated through 24-h recall. The NOVA system was used to identify ultra-processed foods, i.e. industrial formulations manufactured from substances derived from foods and typically added of flavours, colours and other cosmetic additives, such as soft drinks, confectionery, sweet or savoury packaged snacks, microwaveable frozen meals and fast food dishes. Measured weight, height and waist circumference (WC) data were used to calculate the body mass index (BMI) and diagnosis of obesity and abdominal obesity. Regression models were used to evaluate the association of dietary share of ultra-processed foods (quintiles) and obesity indicators, adjusting for socio-demographic variables, physical activity and smoking. Results: Significant (P-trend &le;&thinsp;0.001) direct dose&ndash;response associations between the dietary share of ultra-processed foods and indicators of obesity were found after adjustment. In the multivariable regression analysis, those in the highest quintile of ultra-processed food consumption had significantly higher BMI (0.97&thinsp;kg/m2; 95% CI 0.42, 1.51) and WC (1.92&thinsp;cm; 95% CI 0.57, 3.27) and higher odds of having obesity (OR&thinsp;=&thinsp;1.61; 95% CI 1.27, 2.04) and abdominal obesity (OR&thinsp;=&thinsp;1.38; 95% CI 1.10, 1.72) compared with those in the lowest quintile of consumption. Subgroup analyses showed that the trend towards positive associations for all obesity indicators remained in all age groups, sex and physical activity level. Conclusion: The findings add to the growing evidence that ultra-processed food consumption is associated with obesity and support the potential role of ultra-processed foods in contributing to obesity in Australia