HLA-A, -B, -DR allele group frequencies in 7007 kidney transplant list patients in 27 UK centres.

This observational study aims to determine the HLA specificity frequencies of patients on the UK renal transplant list, which can be used as a resource for those laboratories that support the UK renal transplant programme. Whilst the HLA specificity frequencies may differ from that of the general population, it is the individuals on the transplant list who are in need of a new kidney, which has to be provided from the general population. Any differences in protein allele frequencies between this patient population and the general population are likely to be minimal because of the very large number of patients included. The HLA-A, -B and -DR allele group frequencies from 7007 patients on the UK kidney transplant list (August, 2009) were analysed. HLA types had been submitted to NHSBT to register patients on the UK deceased donor kidney waiting list. The data were submitted from 27 different registering centres throughout the UK. Within this data set, 25 different HLA-A, 50 HLA-B and 18 HLA-DR allele groups were present. The most common allele groups at each locus were -A2 (phenotype frequency 42.6%), -B44 (phenotype frequency 23.3%) and -DR4 (phenotype frequency 29.8%). The least common allele groups at each locus were -A19, - A43, -B16, -B21, -B22, -B83 and -DR5. Reports of HLA frequency (protein allotype) data from populations as large as this are not readily available adding value to this observational study.

Is length of stay in hospital a stable proxy for injury severity?

RESEARCH QUESTION: Is length of stay (LoS) in hospital a stable proxy for severity of injury when monitoring time trends in serious injury incidence? OBJECTIVE: To investigate whether LoS metrics (mean, median and proportion exceeding several LoS thresholds) have changed over time for injury diagnoses with known severity. DESIGN: Time series investigation. SUBJECTS AND SETTING: New Zealand population admitted to hospital for injury and discharged during the period 1989 to 1998. MAIN OUTCOME MEASURES: Interpolated median and geometric mean lengths of stay, as well as the proportion of cases that have an LoS greater than or equal to 3, 4, 7 and 14 days in hospital. METHODS: ICD-9-CM diagnoses that are approximately homogeneous in regard to severity of injury (ICD-HS diagnoses) were identified. Trends were investigated in the LoS statistics for: injury and non-injury diagnoses combined; all injury diagnoses; major body sites of injury; severity strata; and ICD-HS diagnoses. RESULTS: Almost without exception, there was a decline in the LoS statistics over time for all diagnoses, all injury diagnoses, each body site of injury investigated, severity strata, and the ICD-HS diagnoses. CONCLUSIONS: Reductions in median and geometric mean LoS over time, as well as reductions in the proportion exceeding selected LoS thresholds, were due to factors other than reductions in the incidence of serious injury; for example, changes in service delivery over time. An LoS threshold should not be used as a proxy for severity of injury if the goal is to monitor time trends in injury incidence.

Improving the predictive ability of the ICD-based Injury Severity Score.

OBJECTIVE: To assess whether the use of integrated hospitalization and mortality data sources and/or the inclusion of comorbidity improve the predictive ability of the International Classification of Disease (ICD)-based Injury Severity Score (ICISS). DESIGN: Models using either the ICISS based solely on hospital discharge data or one of nine modified ICISSs as the predictor variable were assessed on their ability to predict survival using logistic regression modeling. SETTING: New Zealand. Patients or SUBJECTS: Inpatients, with an S00-T89 ICD-10-AM principal diagnosis, and fatalities, with any S00-T89 ICD-10-AM diagnosis, occurring in 2000-2003. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Models were compared in terms of their discrimination (concordance), calibration, and goodness-of-fit. RESULTS: 186 835 cases including 9968 deaths met the inclusion criterion. The modified ICISS that included both mortality data and Charlson comorbid conditions at the ICD-10-AM level had the best concordance and high calibration. Calibration curves indicated that scores using hospital discharge data only to calculate survival risk ratios underestimated mortality, whereas scores using hospital discharge and mortality data overestimated mortality. CONCLUSIONS: Valid measurement of injury severity is important for both meaningful research and surveillance and to assist in classifying information to meet specific injury policy, prevention, and control needs. This study suggests that the predictive ability of ICISS would be improved if both mortality and comorbidity data were included in its calculation.

Late ventricular structure after partial left ventriculectomy.

Nine months after partial ventriculectomy, a 53-year-old man died of progressive heart failure. His heart was examined to determine the alignment of the muscle fibers around the ventricular scar, which was 11 cm long, 1.3 cm thick and 4 cm wide. The scar reached 2 to 12 mm beyond the surgical suture line. The fibers in the middle and subendocardial layers were malaligned, resulting in convergence, compression and regional necrosis.

The effect of a special nurse on patients' knowledge of epilepsy and their emotional state. Epilepsy Evaluation Care Group.

BACKGROUND: People with epilepsy often report being given insufficient information and support. However, there is little evidence from general practice about how much they know and how they feel. AIM: To describe social differences in the knowledge of epilepsy of people with the condition and test the potential effect of a nurse intervention in general practice on patients' knowledge and depression levels. METHOD: A questionnaire that included measures of knowledge, anxiety, and depression was sent to people with epilepsy aged over 15 years who were registered with 37 general practitioners. Responders were randomized to a controlled trial, offering either two appointments with an epilepsy nurse or usual care. Six months later they were reassessed. RESULTS: Two hundred and fifty-one out of 283 (89%) of the patients with epilepsy completed questionnaires and entered the study at Stage 1. One hundred and ninety-six out of 232 (84%) of those who entered the study, who remained in the practices and were eligible, returned questionnaires at Stage 2. The average duration of epilepsy was 23 years (range 2-79 years). There were significant differences in patients' levels of knowledge of epilepsy at Stage 1. Younger people, those who had left school after 16 years of age, those with GCSEs, and people who belonged to self-help groups had higher knowledge levels, and these were independent effects. Older people and those with a recent epilepsy attack had significantly higher depression scores. Knowledge scores did not differ significantly after the nurse intervention (Stage 2). At Stage 2, the risk of depression was less in the group randomized to be offered nurse input; the effect was mainly in a subgroup of patients with no recent epilepsy attack; their risk of depression was a third of the risk in the control group. CONCLUSIONS: Knowledge of epilepsy differs significantly, with social factors and self-help group membership having independent effects. A nurse-run clinic reduced the risk of depression for people with no recent epilepsy attack, but knowledge levels were not affected. This does not exclude the potential for patients learning more about epilepsy; it may be useful to suggest that patients join self-help groups early on.

Mass spectrometry of beta-lactam antibiotics with special reference to ionization by fast atom bombardment (FAB).

The mass spectral characteristics of the majority of penicillin and cephalosporin beta-lactam antibiotics in world-wide clinical use are presented and reviewed. Special attention is given to the spectra recorded under fast atom bombardment (FAB) conditions and novel data on many penicillins and cephalosporins are included. Mass spectrometry features of common degradation products of benzylpenicillin and of some synthetic intermediates are also presented. The data illustrate the value of FAB mass spectrometry in identifying members of this closely related group of antibiotics without need for derivatization.

Head injuries to bicyclists and the New Zealand bicycle helmet law.

The purpose of this study was to examine the effect of helmet wearing and the New Zealand helmet wearing law on serious head injury for cyclists involved in on-road motor vehicle and non-motor vehicle crashes. The study population consisted of three age groups of cyclists (primary school children (ages 5-12 years), secondary school children (ages 13-18 years), and adults (19+ years)) admitted to public hospitals between 1988 and 1996. Data were disaggregated by diagnosis and analysed using negative binomial regression models. Results indicated that there was a positive effect of helmet wearing upon head injury and this effect was relatively consistent across age groups and head injury (diagnosis) types. We conclude that the helmet law has been an effective road safety intervention that has lead to a 19% (90% CI: 14, 23%) reduction in head injury to cyclists over its first 3 years.

On the significance of fiber branching in the human myocardium.

Myocardial tissue exhibits a high degree of organization in that the cardiac muscle fibers are both systematically aligned and highly branched. In this study, the influence and significance of fiber branching is analyzed mathematically. In order to allow for analytic solutions, a regular geometry and simplified constitutive relations are considered. It is found that branching is necessary to stabilize the ventricular wall.

Hip fractures: a future epidemic?

Recent studies from the United Kingdom and Sweden have demonstrated a dramatic rise in the number of people with hip fractures. It is our hypothesis that New Zealand is experiencing a similar rise in the number of hip fractures. The number of elderly people (over age 65 years) admitted to public hospitals in New Zealand over a 38-year period was reviewed. In people over age 75 years, we observed a disproportionate increase in the number of fractures compared with the increase in population. The highest risk group was women over age 85 years. Because of the differing age-specific fracture rates, the proportion of females over age 85 increased from 17% in 1950 to 40% by 1987. Through weighted regression analysis of fracture rate and population predictions, the projected number of fractures in the year 2001 and 2011 was predicted. By 2011 the number of people sustaining hip fractures will more than double. The proportion of the very elderly (85+) will increase from 40 to 65%.

The work-related fatal injury study: numbers, rates and trends of work-related fatal injuries in New Zealand 1985-1994.

AIMS: To determine the number and rates of work-related fatal injuries by employment status, occupation, industry, age and gender in New Zealand 1985-1994. METHODS: Potential cases of work-related injury deaths of persons aged 15-84 years were identified from the national electronic mortality data files. Main exclusions were deaths due to suicide and deaths due to motor vehicle crashes. The circumstances of the deaths of each fatal incident meeting inclusion criteria were then reviewed directly from coronial files to determine work-relatedness. RESULTS: The rate of work-related fatal injury in New Zealand was 5.03/100000 workers per year for the study period. There was a significant decline in crude rate over the study period. However, this was in substantial part accounted for by changes in occupation and industry mix. Older workers, male workers, self-employed workers, and particular occupational groups, all had substantially elevated rates. Agricultural and helicopter pilots, forestry workers and fishery workers had the highest rates. Farmers, forestry workers, and fishery workers also had high numbers of deaths, together accounting for nearly 40% of all deaths. CONCLUSIONS: This study has demonstrated that work-related fatal injury remains a pressing problem for New Zealand. Several areas in urgent need of prevention efforts were highlighted.

Feasibility and effects of nurse run clinics for patients with epilepsy in general practice: randomised controlled trial. Epilepsy Care Evaluation Group.

OBJECTIVE: To test the feasibility and effect of nurse run epilepsy clinics in primary care. DESIGN: A randomised controlled trial of nurse run clinics versus "usual care." SETTING: Six general practices in the South Thames region. SUBJECTS: 251 patients aged over 15 years who were taking anti-epileptic drugs or had a diagnosis of epilepsy and an attack in the past two years who met specified inclusion criteria and had responded to a questionnaire. MAIN OUTCOME MEASURES: Questionnaire responses and recording of key variables extracted from the clinical records before and after the intervention. RESULTS: 127 patients were randomised to a nurse run clinic, of whom 106 (83%) attended. The nurse wrote 28 letters to the general practitioners suggesting changes in epilepsy management. For this intervention group compared with the usual care group there was a highly significant improvement in the level of advice recorded as having been given on drug compliance, adverse drug effects, driving, alcohol intake, and self help groups. CONCLUSIONS: Nurse run clinics for patients with epilepsy were feasible and well attended. Such clinics can significantly improve the level of advice and drug management recorded.

Computation of the alignment of myocardial contractile pathways using a magnetic tablet and an optical method.

The computation of the inclination angle of myocardial contractile pathways, based on the data from (1) optically and (2) manually digitized hearts is described. The measured raw data comprised: (1) A list epi of points on an "epicardial' surface S. (2) For each selected contractile pathway f, a list of points along the contractile pathway. For any point p on a contractile pathway f, the angle of inclination alpha p = alpha p (p,f,S) is defined to be the angle (in degrees) between the tangent tp = tp(f) to the contractile pathway f at the point p and the tangent plane Tvp to the surface S at the surface point up = v(p,S) which is nearest to p. Thus alpha p is a generalization of the imbrication angle of Streeter. The angle of inclination was computed using two separate numerical methods: (1) A discrete method, applying finite differences to the raw data, to compute the tangents tp and the tangent planes Tvp, after which the results were smoothed. (2) A smoothing method in which the data was first smoothed to obtain an approximation Scpi to the epicardial surface and spline approximations to the contractual pathways f. We describe the results for two typical hearts: a manually digitized dilated pig heart and an optically digitized constricted cow heart. For each heart we first present the depths and angles of inclination of typical contractual pathways and then summarize the results in the form of histograms. The results are discussed in detail in the accompanying paper of Lunkenheimer. Redmann et al. [5], where the digitization methods are also described.

The heart muscle's putative "secondary structure'. Functional implications of a band-like anisotropy.

Opinions are divided as to whether the rope-like secondary structure, which Torrent-Guasp dissected out of the myocardial body by the blunt unwinding technique (BUT) reveals some kind of functional compartmentation of the heart muscle. The myocardial fibres are aligned parallel to the fibre disruption (cleavage) plane, along which the band has been prepared but they are not necessarily aligned parallel to the long axis of the band. Inconsistencies in the myocardial rope model arise from the obligatory zones of transmural inflection, which are obvious in the base and the apex of both ventricles. They are, however, merely discernible in the midzone of the left ventricular cone. The investigator experienced in BUT knows that the cleavage plane is not unique. We doubt the assumption that the rope structure is the predominant stress transmission pathway, because the fibre strand peel-off technique (SPOT) delivers irregular fibre disruption planes which are definitely different from those which Torrent-Guasp prepares. The rope-like fibre arrangement could be just a redundant structure, a remnant of past developmental steps without, however, any functional implication to the human heart. On the other hand, peeling-off fibre strands from the ventricular wall produces deeply perforating, i.e., oblique transmurally grooved surfaces. Putative functions of force transmission in an oblique transmural direction are (1) ventricular dilation as a function of the variable inclination angle with respect to the epicardial surface, (2) monitoring of ventricular wall stress and ventricular size and (3) segmental stiffening which could serve other dependent segments as a punctum fixum.

The heart's fibre alignment assessed by comparing two digitizing systems. Methodological investigation into the inclination angle towards wall thickness.

Myocardial contractile pathways which are not aligned strictly parallel to the heart's epicardial surface, give rise to forces which also act in the ventricular dilating direction. We developed a method which allows us to assess any fibre orientation in the three-dimensional myocardial weave. Decollagenized hearts were prepared by peeling-off fibre strands, following their main fibre orientation down to near the endocardium. In the subepicardium the strands followed a course more or less parallel to the epicardium, whereas from the mid-wall on they tended to dive progressively deeper into the wall. The preparation displays more or less rugged surfaces rather than smooth layers. The grooves and crests on the exposed surfaces were sequentially digitized by two methods: (1) Using a magnet tablet (3 Draw Digitizer System, Polhemus, Cochester VTO 5446, USA) on a dilated pig heart we manually followed the crests using a stylus, handling each groove and crest as an individual contractile pathway. (2) A constricted cow heart was digitized using a contact-free optical system (opto TOP, Dr. Breuckmann, Meersburg, Germany), which is based on the principle of imaging triangulation. Using specially developed software the inclination angles of selected crests and grooves with respect to the epicardial surface were calculated. The two digitizing methods yield comparable results. We found a depth- and side-specific weave component inclined to the epi-endocardial direction. This oblique netting component was more pronounced in the inner 1/3 of the wall than in the subepicardium. The inclination angle probably increases with increasing wall thickness during the ejection period. Manual digitizing is an easy and fast method which delivers consistent results comparable with those obtained by the cumbersome high resolution optical method. The rationales for the assessment of transmural fibre inclination are (1) the putative existence of dilating forces inherent in the myocardial weave and (2) the possible overproportional increase in the oblique transmural weave component during myocardial hypertrophy, which would entail a reduction in efficiency of ventricular performance in terms of haemodynamic work.

The assessment of intramural stress alignment on the beating heart in situ using micro-ergometry: functional implications.

The main local stress transmission pathways in the left ventricular base, midportion and apex in up to seven layers have been assessed in normal dog and porcine hearts, in hypertrophied dog hearts, and in three pig hearts having undergone a temporary left ventricular outflow stricture. The rotational sensitivity of needle force probes was used to determine the focal surface-parallel direction of the myocardial tension vector. In all places investigated the orientation of the force transmission pathways differs slightly from the morphologically determined fibre alignment. Vector rotation upon an axis normal to the epicardial surface is definitely tempered as compared to fibre rotation. Alterations in the force transmission pathways assessed in hypertrophied dog hearts by micro-ergometry qualitatively confirm structural remodelling in so far as an irregularity in the transmural rotation of the main stress vector was found. The measured disparities between the alignment of the myocardial fibre weave and the direction of stress transmission both in the normal and the diseased heart is widely individual, and hence, scattering of the data is marked. However, it must also be called into consideration that the measured orientation of force vectors is that at the moment of highest developed force, only. Further investigations will elucidate if discrepancies between that force vector and morphology are less pronounced when the vector is averaged over the entire heart cycle.

Inhomogeneities in wall stress measured by microergometry in the heart muscle in situ.

Microergometry is a method which we have developed as a tool to measure local mesh-tension within the myocardial weave at any measuring site of both ventricles and the septum on the beating heart in situ. In a mapping procedure on pig and dog hearts, both in control conditions and in the hypertrophied state after aortic banding, local mesh-tension was measured in several areas and in up to eight depths proceeding from the epicardium to the endocardium: Probe-to-fibre coupling is definitely more stable in the canine myocardium than in the porcine heart muscle, probably due to a more effective connective tissue fettering of the canine myocardial weave. The observed longitudinal gradient, with the highest tension in the base, of control dog hearts was levelled out in the hypertrophied hearts. Furthermore, in control dog hearts mesh-tension in the subepi- and subendocardial layers was higher than in the midlayers. This pronounced midlayerhypotension was smoothed in the hypertrophied hearts. Further studies will be dedicated to the question of whether the impact of ventricular size and shape on intersegmental stress transmission is determined by the Frank-Starling mechanism alone or whether protracted remodelling processes on the level of the local fibre weave cause slow coupling alterations.

The difficult access to morphology of the heart: clinical implications.

The literature on the morphology of the heart is reviewed within the context of recent histological findings. There is strong evidence for a dualistic myocardial function, whereby both ventricular constricting and expanding forces are supposed to act synchronously although with variable effect over the heart cycle.The morphological basis of this dualistic myocardial function is the contorted rope-like structure worn into the bulk of the heart muscle. Opinions are divided about the invasiveness of blunt preparation on the heat denatured heart by which the fascicular architecture is carved out of the muscle. Histology confirms the existence of a fascicular substructure. It results from an inhomogeneous repartition of myocardial fibre branchings and the arrangement of the delicate connective tissue netting by which myocardial strands are bundled and wrapped. One important feature of the fascicular structure of the heart muscle is an oblique transmurally arranged element which yields a force vector opposing systolic wall thickening. This structural element which acts in the direction of ventricular dilation probably gains pathological import in some cases of architectural remodelling, namely in myocardial fibrosis and hypertrophy.

The composition of drinking water and the prevalence of anencephalus and spina bifida in New Zealand.

A study was conducted in a cohort of New Zealand births on the prevalence of anencephalus and spina bifida in relation to various chemical elements in the drinking water. Cases were ascertained from national infant mortality and late fetal death records, and public hospital records and consisted of still and live births (of 28 or more weeks gestation) during 1978-1982 with anencephalus or spina bifida diagnosed either at birth or during the first year of life. The 460 cases were matched with their official birth registration records and a sample of 5000 control births was randomly selected from all non-NTD still- and livebirths. Drinking water data were obtained from a national surveillance program. Iron was the only water element to be included in the stepwise multiple logistic regression model of anencephalus prevalence, and magnesium, sulphate, and nitrate nitrogen were retained in the spina bifida model. This indicates a statistically significant association between these elements and the respective outcome. The results for iron and nitrate nitrogen were contrary to findings from previous studies. Despite the methodological problems associated with such ecological studies, there are indications that the constituents of a water supply may have an impact on the risk of NTDs.

Use of alcohol intoxication codes for serious non-fatal hospitalised injury.

AIM: To determine the extent to which ICD-10 alcohol intoxication codes are used for serious hospitalised injury and the distribution of these codes according to gender, age, injury mechanism and intent, severity of injury, and whether the patient was treated in an Intensive Care Unit. DESIGN: Cross-sectional study. SETTING: New Zealand. PARTICIPANTS: All injury hospital discharges in 2010 that met specified severity criteria. MEASUREMENTS: Cases which had a measurement of BAC (Y90) coded, or only a subjective assessment of alcohol intoxication (F10.0). FINDINGS: 2.5% had a blood alcohol recorded (Y90) and a further 3% were coded as being intoxicated but there was no blood alcohol code. All factors investigated were shown to be independently associated with the assignation of codes. Notable findings were the elevated odds of an alcohol code for males, assault and the more severe injuries. CONCLUSIONS: Assessment of alcohol intoxication among seriously injured persons appears to be very uncommon. The development of a standardised instrument for clinical judgement of intoxication would be highly desirable.