Microvascular arterial disease of the brain and the heart: a shared pathogenesis.

Microvascular arterial disease in the heart manifest as coronary microvascular dysfunction. This condition causes microvascular angina and is associated increased morbidity and mortality. Microvascular arterial disease in the brain is referred to as cerebrovascular small vessel disease. This is responsible for 45% of dementias and 25% of ischaemic strokes. The heart and brain share similar vascular anatomy and common pathogenic risk factors are associated with the development of both coronary microvascular dysfunction and cerebrovascular small vessel disease. Microvascular disease in the heart and brain also appear to share common multisystem pathophysiological mechanisms. Further studies on diagnostic approaches, epidemiology and development of disease-modifying therapy seem warranted.

Prescribing error at hospital discharge: a retrospective review of medication information in an Irish hospital.

BACKGROUND: Prescribing error may result in adverse clinical outcomes leading to increased patient morbidity, mortality and increased economic burden. Many errors occur during transitional care as patients move between different stages and settings of care. AIM: To conduct a review of medication information and identify prescribing error among an adult population in an urban hospital. METHODS: Retrospective review of medication information was conducted. Part 1: an audit of discharge prescriptions which assessed: legibility, compliance with legal requirements, therapeutic errors (strength, dose and frequency) and drug interactions. Part 2: A review of all sources of medication information (namely pre-admission medication list, drug Kardex, discharge prescription, discharge letter) for 15 inpatients to identify unintentional prescription discrepancies, defined as: "undocumented and/or unjustified medication alteration" throughout the hospital stay. RESULTS: Part 1: of the 5910 prescribed items; 53 (0.9%) were deemed illegible. Of the controlled drug prescriptions 11.1% (n = 167) met all the legal requirements. Therapeutic errors occurred in 41% of prescriptions (n = 479) More than 1 in 5 patients (21.9%) received a prescription containing a drug interaction. Part 2: 175 discrepancies were identified across all sources of medication information; of which 78 were deemed unintentional. Of these: 10.2% (n = 8) occurred at the point of admission, whereby 76.9% (n = 60) occurred at the point of discharge. CONCLUSIONS: The study identified the time of discharge as a point at which prescribing errors are likely to occur. This has implications for patient safety and provider work load in both primary and secondary care.

General practitioner views on the determinants of test ordering: a theory-based qualitative approach to the development of an intervention to improve immunoglobulin requests in primary care.

BACKGROUND: Research suggests that variation in laboratory requesting patterns may indicate unnecessary test use. Requesting patterns for serum immunoglobulins vary significantly between general practitioners (GPs). This study aims to explore GP's views on testing to identify the determinants of behaviour and recommend feasible intervention strategies for improving immunoglobulin test use in primary care. METHODS: Qualitative semi-structured interviews were conducted with GPs requesting laboratory tests at Cork University Hospital or University Hospital Kerry in the South of Ireland. GPs were identified using a Health Service Executive laboratory list of GPs in the Cork-Kerry region. A random sample of GPs (stratified by GP requesting patterns) was generated from this list. GPs were purposively sampled based on the criteria of location (urban/rural); length of time qualified; and practice size (single-handed/group). Interviews were carried out between December 2014 and February 2015. Interviews were transcribed verbatim using NVivo 10 software and analysed using the framework analysis method. Emerging themes were mapped to the theoretical domains framework (TDF), which outlines 12 domains that can enable or inhibit behaviour change. The behaviour change wheel and behaviour change technique (BCT) taxonomy were then used to identify potential intervention strategies. RESULTS: Sixteen GPs were interviewed (ten males and six females). Findings suggest that intervention strategies should specifically target the key barriers to effective test ordering, while considering the context of primary care practice. Seven domains from the TDF were perceived to influence immunoglobulin test ordering behaviours and were identified as 'mechanisms for change' (knowledge, environmental context and resources, social/professional role and identity, beliefs about capabilities, beliefs about consequences, memory, attention and decision-making processes and behavioural regulation). Using these TDF domains, seven BCTs emerged as feasible 'intervention content' for targeting GPs' ordering behaviour. These included instructions on how to effectively request the test (how to perform behaviour), information on GPs' use of the test (feedback on behaviour), information about patient consequences resulting from not doing the test (information about health consequences), laboratory/consultant-based advice/education (credible source), altering the test ordering form (restructuring the physical environment), providing guidelines (prompts/cues) and adding interpretive comments to the results (adding objects to the environment). These BCTs aligned to four intervention functions: education, persuasion, environmental restructuring and enablement. CONCLUSIONS: This study has effectively applied behaviour change theory to identify feasible strategies for improving immunoglobulin test use in primary care using the TDF, 'behaviour change wheel' and BCT taxonomy. The identified BCTs will form the basis of a theory-based intervention to improve the use of immunoglobulin tests among GPs. Future research will involve the development and evaluation of this intervention.

Does contact with a podiatrist prevent the occurrence of a lower extremity amputation in people with diabetes? A systematic review and meta-analysis.

OBJECTIVE: To determine the effect of contact with a podiatrist on the occurrence of Lower Extremity Amputation (LEA) in people with diabetes. DESIGN AND DATA SOURCES: We conducted a systematic review of available literature on the effect of contact with a podiatrist on the risk of LEA in people with diabetes. Eligible studies, published in English, were identified through searches of PubMed, CINAHL, EMBASE and Cochrane databases. The key terms, 'podiatry', 'amputation' and 'diabetes', were searched as Medical Subject Heading terms. Reference lists of selected papers were hand-searched for additional articles. No date restrictions were imposed. STUDY SELECTION: Published randomised and analytical observational studies of the effect of contact with a podiatrist on the risk of LEA in people with diabetes were included. Cross-sectional studies, review articles, chart reviews and case series were excluded. Two reviewers independently assessed titles, abstracts and full articles to identify eligible studies and extracted data related to the study design, characteristics of participants, interventions, outcomes, control for confounding factors and risk estimates. ANALYSIS: Meta-analysis was performed separately for randomised and non-randomised studies. Relative risks (RRs) with 95% CIs were estimated with fixed and random effects models as appropriate. RESULTS: Six studies met the inclusion criteria and five provided data included in meta-analysis. The identified studies were heterogenous in design and included people with diabetes at both low and high risk of amputation. Contact with a podiatrist did not significantly affect the RR of LEA in a meta-analysis of available data from randomised controlled trials (RCTs); (1.41, 95% CI 0.20 to 9.78, 2 RCTs) or from cohort studies; (0.73, 95% CI 0.39 to 1.33, 3 Cohort studies with four substudies in one cohort). CONCLUSIONS: There are very limited data available on the effect of contact with a podiatrist on the risk of LEA in people with diabetes.

Factors associated with staffing provision and medical equipment acquisition in Irish general practice.

GPs form an integral part of Irish primary care provision. However, current information concerning general practice structure, staffing and development in Ireland is quite limited. This report provides a profile of General Practice in Ireland in 2010 drawing on a national survey of practices using a standardised questionnaire. On average, there are 2.7 GPs per practice, although one in four practices remains single-handed. The majority of practices employ nursing 485 (80.7%) and clerical 549 (91.3%) support. A high proportion of practices have the following items of equipment: ECG machine 496 (82.5%), 24 hour blood pressure monitor 481 (80.1%), spirometer 383 (63.8%), cryotherapy equipment 505 (84%), minor surgery equipment 453 (74.3%) and foetal monitor 484 (80.5%). Using chi-square analysis, we find statistically significant positive relationships between nursing support and possession of each of the six items of medical equipment (chi2 = 81.57, p < 0.01; chi2 = 105.4, p < 0.01; 2 = 38.5, p < 0.01; chi2 = 16.6, p < 0.01; chi2 = 39.5, p < 0.01; = 19.5, p < 0.01) and between practice size and possession of each item of medical equipment (chi2 = 26.3, p < 0.01; chi2 = 45, p < 0.01; chi2 = 16.5, p < 0.01; chi2 = 44.4, p < 0.01; chi2 = 13.8, p < 0.01; chi2 = 14.7, p < 0.01).

Experiment-model interaction for analysis of epicardial activation during human ventricular fibrillation with global myocardial ischaemia.

We describe a combined experiment-modelling framework to investigate the effects of ischaemia on the organisation of ventricular fibrillation in the human heart. In a series of experimental studies epicardial activity was recorded from 10 patients undergoing routine cardiac surgery. Ventricular fibrillation was induced by burst pacing, and recording continued during 2.5 min of global cardiac ischaemia followed by 30 s of coronary reflow. Modelling used a 2D description of human ventricular tissue. Global cardiac ischaemia was simulated by (i) decreased intracellular ATP concentration and subsequent activation of an ATP sensitive K⁺ current, (ii) elevated extracellular K⁺ concentration, and (iii) acidosis resulting in reduced magnitude of the L-type Ca²âº current I(Ca,L). Simulated ischaemia acted to shorten action potential duration, reduce conduction velocity, increase effective refractory period, and flatten restitution. In the model, these effects resulted in slower re-entrant activity that was qualitatively consistent with our observations in the human heart. However, the flattening of restitution also resulted in the collapse of many re-entrant waves to several stable re-entrant waves, which was different to the overall trend we observed in the experimental data. These findings highlight a potential role for other factors, such as structural or functional heterogeneity in sustaining wavebreak during human ventricular fibrillation with global myocardial ischaemia.

Organization of ventricular fibrillation in the human heart: experiments and models.

Sudden cardiac death is a major health problem in the industrialized world. The lethal event is typically ventricular fibrillation (VF), during which the co-ordinated regular contraction of the heart is overthrown by a state of mechanical and electrical anarchy. Understanding the excitation patterns that sustain VF is important in order to identify potential therapeutic targets. In this paper, we studied the organization of human VF by combining clinical recordings of electrical excitation patterns on the epicardial surface during in vivo human VF with simulations of VF in an anatomically and electrophysiologically detailed computational model of the human ventricles. We find both in the computational studies and in the clinical recordings that epicardial surface excitation patterns during VF contain around six rotors. Based on results from the simulated three-dimensional excitation patterns during VF, which show that the total number of electrical sources is 1.4 +/- 0.12 times greater than the number of epicardial rotors, we estimate that the total number of sources present during clinically recorded VF is 9.0 +/- 2.6. This number is approximately fivefold fewer compared with that observed during VF in dog and pig hearts, which are of comparable size to human hearts. We explain this difference by considering differences in action potential duration dynamics across these species. The simpler spatial organization of human VF has important implications for treatment and prevention of this dangerous arrhythmia. Moreover, our findings underline the need for integrated research, in which human-based clinical and computational studies complement animal research.

A computational study of mother rotor VF in the human ventricles.

Sudden cardiac death is one of the major causes of death in the industrialized world. It is most often caused by a cardiac arrhythmia called ventricular fibrillation (VF). Despite its large social and economical impact, the mechanisms for VF in the human heart yet remain to be identified. Two of the most frequently discussed mechanisms observed in experiments with animal hearts are the multiple wavelet and mother rotor hypotheses. Most recordings of VF in animal hearts are consistent with the multiple wavelet mechanism. However, in animal hearts, mother rotor fibrillation has also been observed. For both multiple wavelet and mother rotor VF, cardiac heterogeneity plays an important role. Clinical data of action potential restitution measured from the surface of human hearts have been recently published. These in vivo data show a substantial degree of spatial heterogeneity. Using these clinical restitution data, we studied the dynamics of VF in the human heart using a heterogeneous computational model of human ventricles. We hypothesized that this observed heterogeneity can serve as a substrate for mother rotor fibrillation. We found that, based on these data, mother rotor VF can occur in the human heart and that ablation of the mother rotor terminates VF. Furthermore, we found that both mother rotor and multiple wavelet VF can occur in the same heart depending on the initial conditions at the onset of VF. We studied the organization of these two types of VF in terms of filament numbers, excitation periods, and frequency domains. We conclude that mother rotor fibrillation is a possible mechanism in the human heart.

Alcohol--how much is too much?

The aims of this study were to examine perceptions of what a sample of students and graduates consider an excessive alcohol intake to be and it's effect on their health. 115 University College Cork (UCC) students and 133 UCC graduates were questioned about their opinions of an acceptable weekly intake of alcohol. The results reveal dramatic changes in drinking habits over recent decades. Students began drinking earlier than graduates and are far more accepting of greater amounts of alcohol being consumed. The student's average opinion of what constituted an excessive weekly alcohol intake was 26.5 units of alcohol/week whereas the graduates felt over 18 units/week was too much. We concluded that even amongst these highly educated cohorts there is a low level of awareness of safe limits of alcohol consumption.

Targeted nNOS gene transfer into the cardiac vagus rapidly increases parasympathetic function in the pig.

Nitric oxide (NO) derived from neuronal nitric oxide synthase (nNOS) facilitates cardiac vagal neurotransmission and bradycardia in vitro. Here we provide evidence of rapid (within 9 h) protein expression and increased vagal responsiveness in vivo following targeted gene transfer of nNOS into the cardiac vagus of the pig. Right vagi were injected with vector encoding nNOS (Ad.nNOS) or saline, while left vagi received an injection of vector encoding enhanced green fluorescent protein (Ad.eGFP). Enhanced nNOS protein expression was detected exclusively in the right vagus nerve, with no evidence of iNOS expression. This was associated with increased baroreflex sensitivity and greater heart rate responsiveness to right vagal stimulation. In contrast, responsiveness of left vagi, or sham-injected right vagi remained constant over the same time period. Basal heart rate was unchanged following gene transfer, suggesting no change in vagal tone. These results support the pre-/post-ganglionic synapse as a site for NO-mediated facilitation of vagal bradycardia in the pig. In addition they demonstrate in vivo that functional gene expression induced with adenoviral vectors occurs earlier than first thought, and may therefore, provide a novel intervention to acutely modulate the neural control of cardiac excitability.

The computational performance of a high-order coupled FEM/BEM procedure in electropotential problems.

This paper presents a thorough analysis of the computational performance of a coupled cubic Hermite boundary element/finite element procedure. This C1 (i.e., value and derivative continous) method has been developed specifically for electropotential problems, and has been previously applied to torso and skull problems. Here, the behavior of this new procedure is quantified by solving a number of dipole in spheres problems. A detailed set of results generated with a wide range of the various input parameters (such as dipole orientation, location, conductivity, and solution method used in each spherical shell [either finite element or boundary elements]) is presented. The new cubic Hermite boundary element procedure shows significantly better accuracy and convergence properties and a significant reduction in CPU time than a traditional boundary element procedure which uses linear or constant elements. Results using the high-order method are also compared with other computational methods which have had quantitative results published for electropotential problems. In all cases, the high-order method offered a significant improvement in computational efficiency by increasing the solution accuracy for the same, or fewer, solution degrees of freedom.

Prescribing new drugs: qualitative study of influences on consultants and general practitioners.

OBJECTIVE: To explore consultants' and general practitioners' perceptions of the factors that influence their decisions to introduce new drugs into their clinical practice. DESIGN: Qualitative study using semistructured interviews. Monitoring of hospital and general practice prescribing data for eight new drugs. SETTING: Teaching hospital and nearby general hospital plus general practices in Birmingham. PARTICIPANTS: 38 consultants and 56 general practitioners who regularly referred to the teaching hospital. MAIN OUTCOME MEASURES: Reasons for prescribing a new drug; sources of information used for new drugs; extent of contact between consultants and general practitioners; and amount of study drugs used in hospitals and by general practitioners. RESULTS: Consultants usually prescribed new drugs only in their specialty, used few new drugs, and used scientific evidence to inform their decisions. General practitioners generally prescribed more new drugs and for a wider range of conditions, but their approach varied considerably both between general practitioners and between drugs for the same general practitioner. Drug company representatives were an important source of information for general practitioners. Prescribing data were consistent with statements made by respondents. CONCLUSIONS: The factors influencing the introduction of new drugs, particularly in primary care, are more multiple and complex than suggested by early theories of drug innovation. Early experience of using a new drug seems to strongly influence future use.

Giving voice to the lifeworld. More humane, more effective medical care? A qualitative study of doctor-patient communication in general practice.

Mishler (The discourse of medicine. The dialectics of medical interviews. Norwood, NJ: Ablex), applying Habermas's theory of Communicative Action to medical encounters. showed how the struggle between the voice of medicine and the voice of the lifeworld fragmented and suppressed patients' multi-faceted, contextualised and meaningful accounts. This paper investigates and critiques Mishler's premise that this results in inhumane, ineffective medical care. Using a more complex data collection strategy, comprising patient interviews, doctor interviews and transcribed consultations we show more complex relations than emerged from Mishler's analysis. We found four communication patterns across 35 general practice case studies. When doctor and patient both used the voice of medicine exclusively (acute physical complaints) this worked for simple unitary problems (Strictly Medicine). When both doctor and patient engaged with the lifeworld, more of the agenda was voiced (Mutual Lifeworld) and patients were recognised as unique human beings (psychological plus physical problems). Poorest outcomes occurred where patients used the voice of the lifeworld but were ignored (Lifeworld Ignored) or blocked (Lifeworld Blocked) by doctors' use of voice of medicine (chronic physical complaints). The analysis supports the premise that increased use of the lifeworld makes for better outcomes and more humane treatment of patients as unique human beings. Some doctors switched communication strategies in different consultations, which suggests that their behaviour might be open to change. If doctors could be sensitised to the importance of dealing with the concerns of the lifeworld for patients with chronic physical conditions as well as psychological conditions, it might be possible to obtain better care for patients. This would require attention to structural aspects of the healthcare system to enable doctors to work fully within the patient-centred model.

Proton pump inhibitors: a study of GPs' prescribing.

BACKGROUND: There has been a rapid increase in proton pump inhibitor (PPI) prescribing in recent years, and controlling the cost and improving the quality of prescribing is an issue of concern to many GPS: OBJECTIVE: Our aim was to compare GPs' usage of different PPIs and explore how GPs' PPI prescribing changes following the introduction of a cheaper competitor. METHODS: PPI prescribing data (PACT) for 53 GPs, who were selected as regular users of a teaching hospital, were monitored from January 1995 to December 1997. The GPs were located in two adjoining health districts and had been interviewed about influences on their decisions to begin prescribing lansoprazole. The PPI prescribing data were collected for the teaching hospital and the general hospital in the adjoining district. RESULTS: Complete prescribing data were available for 50 GPS: Total PPI prescribing increased throughout the study due mainly to increasing use of the new PPIS: Use of the new PPIs increased from 6 to 24% over 3 years. The proportion of maintenance doses prescribed increased from 3 to 12%. There was a 23-fold difference in total PPI prescribing and an 87-fold difference in lansoprazole prescribing between the highest and lowest prescribers. The uptake of pantoprazole was slower than that of lansoprazole. A rapid increase in the use of lansoprazole by the GPs followed an increase in use in the teaching hospital. CONCLUSION: Hospital prescribing was an important influence on the choice of PPI used by GPS: The wide variation in PPI prescribing suggests that there is scope for improvement in the quality and cost of PPI prescribing.

Noninvasive electrical imaging of the heart: theory and model development.

The aim of this work is to begin quantifying the performance of a recently developed activation imaging algorithm of Huiskamp and Greensite [IEEE Trans. Biomed. Eng. 44:433-446]. We present here the modeling and computational issues associated with this process. First, we present a practical construction of the appropriate transfer matrix relating an activation sequence to body surface potentials from a general boundary value problem point of view. This approach makes explicit the role of different Green's functions and elucidates features (such as the anisotropic versus isotropic distinction) not readily apparent from alternative formulations. A new analytic solution is then developed to test the numerical implementation associated with the transfer matrix formulation presented here and convergence results for both potentials and normal currents are given. Next, details of the construction of a generic porcine model using a nontraditional data-fitting procedure are presented. The computational performance of this model is carefully examined to obtain a mesh of an appropriate resolution to use in inverse calculations. Finally, as a test of the entire approach, we illustrate the activation inverse procedure by reconstructing a known activation sequence from simulated data. For the example presented, which involved two ectopic focii with large amounts of Gaussian noise (100 microV rms) present in the torso signals, the reconstructed activation sequence had a similarity index of 0.880 when compared to the input source.

Effects of material properties and geometry on electrocardiographic forward simulations.

This paper investigates the effect on torso potentials of changes in the material properties of the torso volume conductor and changes in the relative geometry of the heart and torso. The investigations are performed using a number of forward simulations with a high-order coupled finite element/boundary element torso model. This torso model contains descriptions of the epicardium, lungs, skeletal muscle (with a continuously varying fiber field) and subcutaneous fat. The number of nodes, elements and solution degrees-of-freedom used in the computational torso model are considerably smaller than previous torso models of similar complexity. The successful forward simulations in this paper hence demonstrate the use of the high-order coupled approach with realistic problems. The results of the torso simulations show that the torso inhomogeneities do affect the torso potentials but do not affect the distribution or pattern of the torso potentials. The inhomogeneities considered are found to have a varying, but important, effect on the torso potentials. The effect of the subcutaneous fat is found to be more important and the effect of the skeletal muscle is found to be less important than previous reports in the literature. The results also show that the relative geometry of the heart and torso is very important in determining the torso potential magnitudes and distributions.

Patients' unvoiced agendas in general practice consultations: qualitative study.

OBJECTIVE: To investigate patients' agendas before consultation and to assess which aspects of agendas are voiced in the consultation and the effects of unvoiced agendas on outcomes. DESIGN: Qualitative study. SETTING: 20 general practices in south east England and the West Midlands. PARTICIPANTS: 35 patients consulting 20 general practitioners in appointment and emergency surgeries. RESULTS: Patients' agendas are complex and multifarious. Only four of 35 patients voiced all their agendas in consultation. Agenda items most commonly voiced were symptoms and requests for diagnoses and prescriptions. The most common unvoiced agenda items were: worries about possible diagnosis and what the future holds; patients' ideas about what is wrong; side effects; not wanting a prescription; and information relating to social context. Agenda items that were not raised in the consultation often led to specific problem outcomes (for example, major misunderstandings), unwanted prescriptions, non-use of prescriptions, and non-adherence to treatment. In all of the 14 consultations with problem outcomes at least one of the problems was related to an unvoiced agenda item. CONCLUSION: Patients have many needs and when these are not voiced they can not be addressed. Some of the poor outcomes in the case studies were related to unvoiced agenda items. This suggests that when patients and their needs are more fully articulated in the consultation better health care may be effected. Steps should be taken in both daily clinical practice and research to encourage the voicing of patients' agendas.