The Tip of the Iceberg: Finding Patients with Heart Failure with Preserved Ejection Fraction in Primary Care

Background: Heart failure with preserved ejection fraction (HFpEF) is under-identified in primary care. Aim: The aim of this study was to determine what information is available in patients’ primary care practice records that would identify patients with HFpEF. Design and Setting: Record review in two practices in East of England. Methods: Practices completed a case report form on each patient on the heart failure register and sent anonymised echocardiography reports on patients with an ejection fraction (EF) > 50%. Reports were reviewed and data analysed using SPSS. Results: 148 patients on the HF Registers with mean age 77 + 12 years were reviewed. Fifty-three patients (36%) had possible HFpEF based on available information. These patients were older and multi-morbid, including high prevalence of overweight and obesity. Confirmation of diagnosis was not possible as recommended HFpEF diagnostic information (natriuretic peptides, echocardiogram parameters of structural heart disease and diastolic function) was widely inconsistent or absent in these patients. Conclusion: Without correct identification of HFpEF, patient management may be sub-optimal or inappropriate, and lack the needed focus on comorbidities and lifestyle that can improve patient outcomes. We have described in detail the characteristics of many of the patients who probably have HFpEF in a real-world sample, and the improvements and diagnostic information required to better identify them. Identifying more than the tip of the iceberg that is the HFpEF population will allow us to improve the quality of their management, prevent ineffective healthcare and recruit patients into research.This paper presents independent research funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR)

Mapping Epileptic Networks Using Simultaneous Intracranial EEG-fMRI

Background: Potentially curative epilepsy surgery can be offered if a single, discrete epileptogenic zone (EZ) can be identified. For individuals in whom there is no clear concordance between clinical localization, scalp EEG, and imaging data, intracranial EEG (icEEG) may be needed to confirm a predefined hypothesis regarding irritative zone (IZ), seizure onset zone (SOZ), and EZ prior to surgery. However, icEEG has limited spatial sampling and may fail to reveal the full extent of epileptogenic network if predefined hypothesis is not correct. Simultaneous icEEG-fMRI has been safely acquired in humans and allows exploration of neuronal activity at the whole-brain level related to interictal epileptiform discharges (IED) captured intracranially. Methods: We report icEEG-fMRI in eight patients with refractory focal epilepsy who had resective surgery and good postsurgical outcome. Surgical resection volume in seizure-free patients post-surgically reflects confirmed identification of the EZ. IEDs on icEEG were classified according to their topographic distribution and localization (Focal, Regional, Widespread, and Non-contiguous). We also divided IEDs by their location within the surgical resection volume [primary IZ (IZ1) IED] or outside [secondary IZ (IZ2) IED]. The distribution of fMRI blood oxygen level-dependent (BOLD) changes associated with individual IED classes were assessed over the whole brain using a general linear model. The concordance of resulting BOLD map was evaluated by comparing localization of BOLD clusters with surgical resection volume. Additionally, we compared the concordance of BOLD maps and presence of BOLD clusters in remote brain areas: precuneus, cuneus, cingulate, medial frontal, and thalamus for different IED classes. Results: A total of 38 different topographic IED classes were identified across the 8 patients: Focal (22) and non-focal (16, Regional = 9, Widespread = 2, Non-contiguous = 5). Twenty-nine IEDs originated from IZ1 and 9 from IZ2. All IED classes were associated with BOLD changes. BOLD maps were concordant with the surgical resection volume for 27/38 (71%) IED classes, showing statistical global maximum BOLD cluster or another cluster in the surgical resection volume. The concordance of BOLD maps with surgical resection volume was greater (p < 0.05) for non-focal (87.5%, 14/16) as compared to Focal (59%, 13/22) IED classes. Additionally, BOLD clusters in remote cortical and deep brain areas were present in 84% (32/38) of BOLD maps, more commonly (15/16; 93%) for non-focal IED-related BOLD maps. Conclusions: Simultaneous icEEG-fMRI can reveal BOLD changes at the whole-brain level for a wide range of IEDs on icEEG. BOLD clusters within surgical resection volume and remote brain areas were more commonly seen for non-focal IED classes, suggesting that a wider hemodynamic network is at play

Facile one-pot synthesis of amoxicillin-coated gold nanoparticles and their antimicrobial activity

Nanomaterials have been the object of intense study due to promising applications in a number of different disciplines. In particular, medicine and biology have seen the potential of these novel materials with their nanoscale properties for use in diverse areas such as imaging, sensing and drug vectorisation. Gold nanoparticles (GNPs) are considered a very useful platform to create a valid and efficient drug delivery/carrier system due to their facile and well-studied synthesis, easy surface functionalization and biocompatibility. In the present study, stable antibiotic conjugated GNPs were synthesised by a one-step reaction using a poorly water soluble antibiotic, amoxicillin. Amoxicillin, a member of the penicillin family, reduces the chloroauric acid to form nanoparticles and at the same time coats them to afford the functionalised nanomaterial. A range of techniques including UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) were used to ascertain the gold/drug molar ratio and the optimum temperature for synthesis of uniform monodisperse particles in the ca. 30-40 nm size range. Amoxicillin-conjugated gold showed an enhancement of antibacterial activity against Escherichia coli compared to the antibiotic alone

Preliminary study of proton magnetic resonance spectroscopy to assess bone marrow adiposity in the third metacarpus or metatarsus in Thoroughbred racehorses

Background: Magnetic resonance spectroscopy (MRS) has been used to investigate metabolic changes within human bone. It may be possible to use MRS to investigate bone metabolism and fracture risk in the distal third metacarpal/tarsal bone (MC/MTIII) in racehorses. Objectives: To determine the feasibility of using MRS as a quantitative imaging technique in equine bone by using the 1H spectra for the MC/MTIII to calculate fat content (FC). Study Design: Observational cross-sectional study Methods: Limbs from Thoroughbred racehorses were collected from horses that died or were subjected to euthanasia on racecourses. Each limb underwent magnetic resonance imaging (MRI) at 3T followed by single-voxel MRS at 3 regions of interest (ROI) within MC/MTIII (lateral condyle, medial condyle, proximal bone marrow (PBM)). Percentage FC was calculated at each ROI. Each limb underwent computed tomography (CT) and bone mineral density (BMD) was calculated for the same ROIs. All MR and CT images were graded for sclerosis. Histology slides were graded for sclerosis and proximal marrow space was calculated. Pearson or Spearman correlations were used to assess the relationship between BMD, FC and marrow space. Kruskall-Wallis tests were used to check for differences between sclerosis groups for BMD or FC. Results: Eighteen limbs from 10 horses were included. A negative correlation was identified for mean BMD and FC for the lateral condyle (correlation coefficient =-0.60, p=0.01) and PBM (correlation coefficient =-0.5, p=0.04). There was a significant difference between median BMD for different sclerosis grades in the condyles on both MRI and CT. A significant difference in FC was identified between sclerosis groups in the lateral condyle on MRI and CT . Main Limitations: Small sample size. Conclusions: 1H Proton MRS is feasible in the equine MC/MTIII. Further work is required to evaluate the use of this technique to predict fracture risk in racehorses

Sensing distress – towards a blended method for detecting and responding to problematic customer experience events

Excellent Customer Experience (CE) is a strategic priority for many large service organisations in a competitive marketplace. CE should be seamless, and in most cases it is, with customers ordering, paying for and receiving services that align with their expectations. However, in rare cases, an exceptional process event leads to service delivery delay or failure, and both the customer and organ-isation end up in complex recovery situations as a result. Unless this recovery is handled effectively inefficiency, avoidable costs and brand damage can result. So how can organisations sense when these problems are occurring and how can they respond to avoid these negative consequences? Our paper proposes a blended methodology where process mining and qualitative user research com-bine to give a holistic picture of customer experience issues, derived from a par-ticular customer case study. We propose a theoretical model for detecting and responding to customer issues, and discuss the challenges and opportunities of such a model when applied in practice in large service organisations

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, &lt;72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Quality and effectiveness of different approaches to primary care delivery in Brazil

BACKGROUND: Since 1994, Brazil has developed a primary care system based on multidisciplinary teams which include not only a physician and a nurse, but also 4–6 lay community health workers. This system now consists of 26,650 teams, covering 46% of the Brazilian population. Yet relatively few investigations have examined its effectiveness, especially in contrast with that of the traditional multi-specialty physician team approach it is replacing, or that of other existing family medicine approaches placing less emphasis on lay community health workers. Primary health care can be defined through its domains of access to first contact, continuity, coordination, comprehensiveness, community orientation and family orientation. These attributes can be ascertained via instruments such as the Primary Care Assessment Tool (PCATool), and correlated with the effectiveness of care. The objectives of our study are to validate the adult version of this instrument in Portuguese, identify the extent (quality) of primary care present in different models of primary care services, and correlate this extent with measures of process and outcomes in patients with diabetes, hypertension and coronary heart disease (CHD). METHODS/DESIGN: We are conducting a population-based cross-sectional study of primary care in the municipality of Porto Alegre. We will interview a random sample totaling 3000 adults residing in geographic areas covered by four distinct models of primary care of the Brazilian national health system or, alternatively, by one nationally prominent complementary health care service, as well as the physicians and nurses of the health teams of these services. Interviews query perceived quality of care (PCATool-Adult Version), patient satisfaction, and process indicators of management of diabetes, hypertension and known CHD. We are measuring blood pressure, anthropometrics and, in adults with known diabetes, glycated hemoglobin. DISCUSSION: We hope to contribute not only by validating the PCATool-Adult Version for use in Brazil, but also by furnishing ample data concerning the appropriate mix of health care professionals in the primary care team, a question of international import. Once validated, future use of this instrument should help direct advances aiming at improving the quality of primary care in Brazil

Measuring Strategic Uncertainty in Coordination Games

Lecture on the first SFB/TR 15 meeting, Gummersbach, July, 18 - 20, 2004This paper explores predictability of behavior in coordination games with multiple equilibria. In a laboratory experiment we measure subjects' certainty equivalents for three coordination games and one lottery. Attitudes towards strategic uncertainty in coordination games are related to risk aversion, experience seeking, gender and age. From the distribution of certainty equivalents among participating students we estimate probabilities for successful coordination in a wide range of coordination games. For many games success of coordination is predictable with a reasonable error rate. The best response of a risk neutral player is close to the global-game solution. Comparing choices in coordination games with revealed risk aversion, we estimate subjective probabilities for successful coordination. In games with a low coordination requirement, most subjects underestimate the probability of success. In games with a high coordination requirement, most subjects overestimate this probability. Data indicate that subjects have probabilistic beliefs about success or failure of coordination rather than beliefs about individual behavior of other players