Reducing Unnecessary Noninvasive Testing for Inpatients With Unstable Angina: The RUNIT Protocol.

BACKGROUND: Routine inpatient transthoracic echocardiography (TTE) for patients with unstable angina is common, but it anecdotally adds little value to clinical care. A practice audit at our academic hospital demonstrated that 61.5% of patients with troponin-negative chest pain (TNCP) had normal left ventriculography (LVG) during coronary angiography and normal TTE on the same admission (duplicate testing). METHODS: We developed the Reducing Non-Invasive Testing (RUNIT) protocol, a clinical algorithm applied by clinical nurses to patient with TNCP. We performed a prospective assessment of rate of duplicate testing before and after intervention. If patients met certain simple clinical criteria, their TTE was cancelled (RUNIT positive). Patients then proceeded to have either coronary angiography with LVG or noninvasive risk stratification. We aimed to reduce duplicate testing by 25% over a 1-year period. Balancing measures included pathology on ordered TTEs, 30-day readmission, length of stay, and number of LVG. RESULTS: Among 254 patients admitted with TNCP over 12 months, we reduced duplicate testing from 61.5% (before intervention) to 34% (P = 0.001). There was no clinical difference in 30-day readmission (0.9% vs 0.7%), and length of stay was significantly shorter in RUNIT positive (3.48 vs 4.16 days, P = 0.02). The majority of duplicate TTEs did not reveal any management-informing pathology. RUNIT-positive patients underwent more LVG than RUNIT-negative patients (78.3% vs 62.8%, P = 0.008). CONCLUSION: We achieved a sustained reduction in reflexive TTE ordering in patients with TNCP, and we discuss the potential of nursing-led interventions to address other areas of low value care in cardiology.

CONTEXTE: La réalisation systématique d'une échocardiographie transthoracique (ETT) chez les patients hospitalisés pour angine instable est une pratique courante, qui n'apporte toutefois qu'une valeur anecdotique aux soins cliniques. Un audit des pratiques en vigueur dans l'hôpital universitaire auquel nous sommes rattachés a révélé que 61,5 % des patients ayant une douleur thoracique sans élévation de la troponine (DTST) présentaient une ventriculographie gauche (VGG) normale à la coronarographie et une ETT normale lors de la même admission (tests effectués en double). MÉTHODOLOGIE: Nous avons mis au point le protocole RUNIT ( R ed u cing N on- I nvasive T esting, réduction des tests non invasifs), un algorithme clinique appliqué par le personnel infirmier clinicien aux patients présentant une DTST. Nous avons ensuite mené une évaluation prospective du taux de réalisation de tests en double avant et après l'intervention. Si les patients répondaient à certains critères cliniques simples, l'ETT n'était pas effectuée (score RUNIT positif). Les patients ont par la suite été soumis soit à une coronarographie et à une VGG, soit à une stratification du risque associé aux méthodes non invasives. Notre objectif était de réduire de 25 % la réalisation de tests en double sur une période de 1 an. Les mesures de compensation comprenaient une évaluation pathologique des résultats des ETT demandées, la réadmission à 30 jours, la durée de l'hospitalisation et le nombre de VGG. Résultats : Parmi les 254 patients admis en raison d'une DTST sur une période de 12 mois, nous avons réduit la réalisation de tests en double de 61,5 % (avant l'intervention) à 34 % (p = 0,001). Il n'y avait pas de différence clinique quant au taux de réadmission à 30 jours (0,9 % vs 0,7 %), et l'hospitalisation a été beaucoup plus courte chez les patients ayant obtenu un score RUNIT positif (3,48 vs 4,16 jours, P = 0,02). La majorité des ETT réalisées en double n'ont mis au jour aucune caractéristique pathologique permettant d'éclairer la prise en charge. Les patients qui ont obtenu un score RUNIT positif ont par ailleurs subi un plus grand nombre de VGG que ceux qui ont obtenu un score négatif (78,3 % vs 62,8 %, p = 0,008). CONCLUSION: Nous avons réussi à réduire de manière soutenue la réalisation systématique d'ETT chez les patients présentant une DTST, et nous traitons de la possibilité de mettre en place des protocoles à appliquer par le personnel infirmier afin de réduire l'exécution d'autres interventions n'apportant que peu de valeur aux soins en cardiologie.

Author Correction: Establishment and equilibrium levels of deleterious mutations in large populations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Establishment and equilibrium levels of deleterious mutations in large populations.

Analytical and statistical stochastic approaches are used to model the dispersion of monogenic variants through large populations. These approaches are used to quantify the magnitude of the selective advantage of a monogenic heterozygous variant in the presence of a homozygous disadvantage. Dunbar's results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic effective community size from which an individual can select mates. By envisaging human community structure as a network where social proximity rather than physical geography predominates, a significant simplification is achieved, implicitly accounting for the effects of migration and consanguinity, and with population structure and genetic drift becoming emergent features of the model. Effective community size has a dramatic effect on the probability of establishing beneficial alleles. It also affects the eventual equilibrium values that are reached in the case of variants conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific allele in a population, without requiring prior information regarding its phenotypic manifestation.

Stacking disorder in silicon carbide supported cobalt crystallites: an X-ray diffraction, electron diffraction and high resolution electron microscopy study.

Supported cobalt Fischer-Tropsch catalysts are characteristically nanoparticulate and the reduced SiC supported catalyst was found to contain both HCP and FCC polymorphs. This is reflected in the powder XRD patterns and generally there is a poor fit between the experimental and calculated diffractograms. This was ascribed to small crystallite sizes and the occurrence of disorder, manifested as peak broadening and peak shifts. Selected area electron diffraction data of suitably oriented cobalt catalyst grains on silicon carbide supports show non-periodic disorder in the zone axis orientations that contain the common (001) (HCP) and (111) (FCC) reciprocal lattice planes. Both FCC and HCP polymorphs are present in the same grains and these show disorder mainly in the HCP component. The disorder is further examined using high angle annular dark field (HAADF) scanning transmission electron microscopy at atomic resolution and the stacking sequences elucidated. Random sequences of mainly FCC are interrupted by HCP sequences and twin surfaces with reverse stacking sequences are also present. This study highlights the presence of significant disorder in cobalt catalyst grains confirmed by HAADF microscopy.

Efficiency of a closed-coupled solar pasteurization system in treating roof harvested rainwater.

Many studies have concluded that roof harvested rainwater is susceptible to chemical and microbial contamination. The aim of the study was thus to conduct a preliminary investigation into the efficiency of a closed-coupled solar pasteurization system in reducing the microbiological load in harvested rainwater and to determine the change in chemical components after pasteurization. The temperature of the pasteurized tank water samples collected ranged from 55 to 57°C, 64 to 66°C, 72 to 74°C, 78 to 81°C and 90 to 91°C. Cations analyzed were within drinking water guidelines, with the exception of iron [195.59 µg/L (55°C)-170.1 µg/L (91°C)], aluminum [130.98 µg/L (78°C)], lead [12.81 µg/L (55°C)-13.2 µg/L (91°C)] and nickel [46.43 µg/L (55°C)-32.82 µg/L (78°C)], which were detected at levels above the respective guidelines in the pasteurized tank water samples. Indicator bacteria including, heterotrophic bacteria, Escherichia coli and total coliforms were reduced to below the detection limit at pasteurization temperatures of 72°C and above. However, with the use of molecular techniques Yersinia spp., Legionella spp. and Pseudomonas spp. were detected in tank water samples pasteurized at temperatures greater than 72°C. The viability of the bacteria detected in this study at the higher temperature ranges should thus be assessed before pasteurized harvested rainwater is used as a potable water source. In addition, it is recommended that the storage tank of the pasteurization system be constructed from an alternative material, other than stainless steel, in order for a closed-coupled pasteurization system to be implemented and produce large quantities of potable water from roof harvested rainwater.

Altered homeostasis of systemic glucocorticoids as related to obesity, glucose tolerance, and smoking.

The hypothalamic-pituitary-adrenal axis is supposed to be involved in the pathogenesis of the metabolic disorders. Differences in adipose tissues and parameters of insulin resistance are linked to steroid homeostasis. We assessed the correlation of fat tissue distribution, gender, and glucose control with levels of systemic corticosteroid-binding globulin (CBG), free cortisol (FuF), and total cortisol (FuM). Data of 1 114 patients with overweight, lipid disorders, and impaired glucose tolerance were collected. Blood samples were sorted according to gender and anthropometric measures. Variable-association was calculated using the Spearman Rank Correlation coefficient and tested for significance (p<0.05 and p<0.01). CBG and FuF were consistently negatively correlated to each weight parameter. Especially in women, fat mass index (FMI) was significantly negatively correlated with CBG-levels. While CBG levels dropped with increasing age, FuF showed an inverse behavior. Glycohemoglobin levels showed negative correlations with CBG while fasting glucose did not. Both changes were associated with significant increases in FuF. All negative correlations to cortisol and its binding globulin with regards to weigh- and glucose-control parameters were absent in smokers compared to nonsmokers. Our observations suggest that different weight parameters correspond to adrenal steroids and their buffer systems. Especially in women, CBG levels might serve as prognostic marker for the fat mass. In addition, CBG levels may predict long term blood glucose control more reliably than FG. However, the value of CBG as an indirect surrogate-marker for obesity and glucose is limited in smokers.

Tactical treatment with copper oxide wire particles and symptomatic levamisole treatment using the FAMACHA(©) system in indigenous goats in South Africa.

Haemonchosis is considered to be the most economically important gastrointestinal disease of small ruminants in the tropics and subtropics. However, chemical anthelmintics, which were the mainstay of control, have been compromised by a high prevalence of resistance worldwide. Copper oxide wire particles (COWP) have been shown to have anthelmintic effects, but few studies have examined their use under field conditions. The use of COWP was therefore evaluated as a tactical anthelmintic treatment in indigenous goats raised under communal farming conditions in Bergville, KwaZulu-Natal Province, South Africa. At the beginning of the summer rainfall season (October 2007), the faecal egg counts of 172 female goats belonging to 15 farmers were determined and this sampling continued every four weeks until the second week of January 2008. The goats within each of the 15 herds were ranked according to their faecal egg counts for this week. The goats were sequentially paired off within each ranking starting with those goats with the highest counts. One goat from each pair was randomly allocated to a treated or control group. Two weeks later, a 4 g COWP bolus was randomly administered to each goat in the treated group. Faecal egg counts were carried out on the goats two weeks following treatment, and the sampling of the goats then proceeded every four weeks until October 2008. Except for the six-week period prior to the administration of the COWP, the goats were examined according to the FAMACHA(©) system and symptomatically treated with 12 mg/kg levamisole when anaemic. The percentage reduction in faecal egg count due to the COWP treatment was 89.0%. Mean pre- and post-treatment faecal egg counts for the COWP-treated group (n=73) were 2347 eggs per gram of faeces (epg) and 264 epg, respectively. The corresponding values for the untreated controls (n=66) were 2652 epg and 2709 epg. The prevalence of Haemonchus spp. larvae in pre- and post-treatment faecal cultures was 72% and 46%, respectively. Symptomatic anthelmintic treatments in combination with mid-summer tactical treatments with COWP appear to be useful strategies for the control of Haemonchus contortus in indigenous goats in this farming system and this approach could have application in other similar agro-ecological zones.

Rietveld and pair distribution function study of Hägg carbide using synchrotron X-ray diffraction.

Fischer-Tropsch (FT) synthesis is an important process in the manufacturing of hydrocarbons and oxygenated hydrocarbons from mixtures of carbon monoxide and hydrogen (syngas). The reduced iron catalyst reacts with carbon monoxide and hydrogen to form bulk Fe(5)C(2) Hägg carbide (χ-HC) during FT synthesis. Arguably, χ-HC is the predominant catalyst phase present in the working iron catalyst. Deactivation of the working catalyst can be due to oxidation of χ-HC to iron oxide, a step-wise decarburization to cementite (θ-Fe(3)C), carbon formation or sintering with accompanying loss of catalytic performance. It is therefore critical to determine the precise crystal structure of χ-HC for the understanding of the synthesis process and for comparison with the first-principles ab initio modelling. Here the results of high-resolution synchrotron X-ray powder diffraction data are reported. The atomic arrangement of χ-HC was confirmed by Rietveld refinement and subsequent real-space modelling of the pair distribution function (PDF) obtained from direct Fourier transformation. The Rietveld and PDF results of χ-HC correspond well with that of a pseudo-monoclinic phase of space group Pi [a = 11.5661 (6) Å, b = 4.5709 (1) Å, c = 5.0611 (2) Å, α = 89.990 (5)°, ß = 97.753 (4)°, γ = 90.195 (4)°], where the Fe atoms are located in three distorted prismatic trigonal and one octahedral arrangement around the central C atoms. The Fe atoms are distorted from the prismatic trigonal arrangement in the monoclinic structure by the change in C atom location in the structure.

Emerging norovirus GII.4 2008 variant detected in hospitalised paediatric patients in South Africa.

BACKGROUND: Noroviruses (NoVs) are important enteric pathogens that cause gastroenteritis worldwide. The first documented NoV outbreaks in South Africa (SA) were described in 1993. The current NoV prevalence and circulating genotypes are unknown. SA lacks NoV outbreak reporting systems and therefore the number and impact of NoV infections is underestimated. OBJECTIVES: This study aimed to determine the prevalence and genetic diversity of NoV infections in hospitalised paediatric patients with gastroenteritis in SA during 2008. STUDY DESIGN: Stool specimens referred for virological analysis from hospitalised children ≤13 years, with gastroenteritis, were screened for rotavirus, human adenovirus and human astrovirus by enzyme immunoassay and for NoV genogroup I (GI), II (GII) and sapovirus by real-time RT-PCR. NoV strains were genotyped, and variants identified, based on sequence and phylogenetic analyses of the 5' end or the full length of the capsid gene, respectively. RESULTS: Rotavirus was the most prevalent virus detected in 24.2% (61/252) of specimens, followed by NoV in 14.3% (35/245) and adenovirus, astrovirus and sapovirus in 9.6%, 6.7% and 4% of specimens, respectively. NoVs were only detected in children ≤2 years. The GII NoVs (89%) predominated and eight types were identified with GII.4 (43%) detected most frequently. The emerging 2008 GII.4 variant represented 80% of the GII.4 strains. CONCLUSIONS: A diverse range of NoV genotypes were identified in hospitalised children with gastroenteritis. The 2008 GII.4 variant was the most frequently detected strain in the study. This is the first report of NoV GII.4 viruses in SA.

Benefits of urea-molasses block supplementation and symptomatic and tactical anthelmintic treatments of communally grazed indigenous goats in the Bulwer area, Kwazulu-Natal Province, South Africa.

This study was carried out with the cooperation of farmers owning communally grazed indigenous goats in southwestern KwaZulu-Natal Province, South Africa, where farmers had identified poor reproductive performance in their herds as one of their major problems. The aim was to quantify the effects of 3 interventions and the interaction between these interventions on goat productivity and gastrointestinal nematode infection. The interventions were: urea-molasses block supplementation during the dry winter seasons of 2004 and 2005, tactical anthelmintic treatment with ivermectin (400 microg/kg) during the wet summer period (on 3 January 2005) and symptomatic treatment with ivermectin (400 microg/kg) of all goats judged anaemic throughout the entire study period. The FAMACHA system was used as a gauge of anaemia. It was noted that goats considered anaemic tended to remain so throughout the study period. The tactical anthelmintic treatment was effective as it markedly reduced (P = 0.066) the summer peak in faecal egg counts and is therefore recommended. By contrast, while the urea-molasses block supplementation appeared to reduce the faecal egg counts immediately following the 2004 supplementation (P < 0.05), this did not hold true in 2005. Interestingly, in the tactically treated anaemic goats, the improvement in the number of kids suckled per doe year-on-year tended to be greater than in the non-anaemic goats. It is considered that the routine symptomatic treatment of anaemic goats may have been a key factor. More detailed investigations into the routine symptomatic treatment of anaemic goats are therefore recommended.

Analysis of viral and genetic factors in South African patients with multiple sclerosis.

A significant association was previously demonstrated between multiple sclerosis (MS) and the functional 5'-(GT)n polymorphism in the promoter region of the SLC11A1 gene, which has been implicated in both autoimmune and infectious disease susceptibility. In the present study the role of viral infection was investigated in South African MS patients in relation to specific SLC11A1 genotypes. Serum and peripheral blood mononuclear cells (PBMC) of 49 MS patients, 33 close relatives and 39 unrelated controls previously genotyped for SLC11A1 were screened for the presence of MS-associated retrovirus (MSRV) and two herpes virus (HHV-6 and EBV) sequences. Expression of the pol gene of MSRV was detected in the serum RNA of 34/49 (69%) MS patients whilst absent in the serum of 39 unrelated healthy control individuals (p < 0.001) but was also present in 23/33 (70%) of the unaffected close relatives of the patients. HHV-6 and EBV sequences were detected in both MS patients and control individuals. The viral sequences were not confined to a specific SLC11A1 genotype. Infection with these viruses is excluded as the primary cause for MS in the South African population since no significant differences were detected between MS patients and their unaffected close family members.

Lack of clinical manifestation of hereditary haemochromatosis in South African patients with multiple sclerosis.

Caucasian South African patients with multiple sclerosis (MS) were screened for the most common hereditary haemochromatosis (HH) mutations, H63D and C282Y, in order to determine the impact of iron overload on clinical outcome of MS. DNA screening for mutations H63D and C282Y in 118 apparently unrelated MS patients did not reveal significant differences in allele frequencies in comparison with a control group from the same population. Of 17 MS patients heterozygous for C282Y, 3 had below normal and none had above normal transferrin saturation levels. One of the index MS patients, and subsequently also her sister who also has MS, tested positive for two copies of mutation C282Y. Determination of iron status revealed high serum ferritin and transferrin saturation levels in both patients. However, the index patient, being unaware of her C282Y status, had received treatment for iron deficiency in the past and her MS symptoms were less severe than those of her sister who has been wheelchair bound for the past 12 years and who did not take iron supplements. Lack of clinical manifestation of HH without any signs of organ damage in the C282Y homozygous MS patients is in accordance with a role of iron dysregulation in the aetiology of MS.

Overrepresentation of the founder PPOX gene mutation R59W in a South African patient with severe clinical manifestation of porphyria.

A patient, who presented with abdominal pain and severe photosensitivity that resulted in scarring and mutilation of the fingers, nose and ears, was referred for biochemical assessment of porphyria and DNA screening. Although these clinical manifestations were suggestive of both acute porphyria and congenital erythropoietic porphyria, the biochemical profile was consistent with variegate porphyria (VP). Analysis of the protoporphyrinogen oxidase (PPOX) gene underlying VP resulted in the identification of the founder mutation R59W in a heterozygous state in this patient. Despite extensive mutation analysis, no other potential disease-causing genetic alterations could be detected in the PPOX gene or the uroporphyrinogen III synthase gene. Slight overrepresentation of the mutant PPOX allele was however, observed repeatedly in DNA of the proband compared to other R59W heterozygotes, including his mother who also tested positive for mutation R59W using restriction enzyme analysis and direct DNA sequencing. Confirmation of this phenomenon by real-time polymerase chain reaction analysis and microsatellite analysis, using highly informative markers flanking the PPOX gene, raised the possibility of partial homozygosity for VP in this patient. This study represents the first report of overrepresentation of mutation R59W in a patient with a severe form of VP. A homozygote for the R59W mutation has never been detected, and the severe clinical manifestation observed in our patient is consistent with the hypothesis that such a genotype will not be compatible with life.

Evaluation of clinical teaching and professional development in a problem- and community-based nursing module.

In South Africa the main focus is on primary health care. This affects the education and training of nurses, and training schools must respond by developing appropriate teaching modules. A school of nursing developed, implemented and revised a problem- and community-based learning module over a period of three years (1996-1998). This student-centered module focuses on students' needs, active participation, collaboration, accountability, self-assessment, self-study, life-long learning and appropriate skills. In the formal clinical teaching environment PBL was the main approach. However, this approach was also supported by a variety of strategies, for example group discussions and scenarios. The knowledge, attitudes and professional development skills acquired in the PBL approach were then applied informally in the community setting (CBE). The purpose of the study was to evaluate a first year clinical teaching module as part of an extensive programme. A quantitative research method, a descriptive design, and a variety of data collection techniques were used. Conclusions were that clinical teaching was effective within the problem- (PBL) and community-based (CBE) approaches; 78% of respondents were positive about the clinical learning environment; 61% stated that expectations were met; 81% preferred group activities, and 67% indicated that they had developed professional skills. Facilitators agreed that clinical teaching met the requirements of PBL & CBE. The pass rate also improved.

Molecular diagnosis of hereditary hemochromatosis: application of a newly-developed reverse-hybridization assay in the South African population.

A recently developed strip-assay for hemochromatosis provides a rapid method for simultaneous detection of multiple mutations, which among others includes the HFE gene mutations V53M, V59M, H63D, H63H, S65C, Q127H, E168Q, and C282Y, previously detected in the general South African population using gel-based mutation-screening methods. The objective of the study was to determine the frequency of the relatively rare mutations in samples selected for altered iron parameters or a family history of hereditary hemochromatosis (HH) as part of the validation process of the assay for routine diagnostic purposes. The study population consisted of 451 individuals previously screened for mutations C282Y and H63D by restriction enzyme analysis in order to confirm or possibly exclude a diagnosis of HH. These individuals were subjected to mutation screening using the commercially available hemochromatosis strip-assay. Previous positive results for mutations C282Y and H63D in 233 individuals confirmed the accuracy of the reverse-hybridization assay. Mutation S65C was detected in 13 Caucasians, including three compound heterozygotes. These constituted 2% (13/600) of the chromosomes without mutations C282Y or H63D. The African-specific HFE mutation V53M was detected in one out of 11 (9%) African subjects screened. Mutation E168Q was detected in a single Caucasian individual together with mutation H63D. Our data demonstrate the value of the strip-based technology in providing a rapid and reliable comprehensive test for simultaneous analysis of multiple mutations.