Breast papilloma is a term that describes an intraductal papillary configuration of the mammary epithelium on macroscopic or microscopic examination. It includes solitary intraductal papillomas, multiple papillomas, papillomatosis, and juvenile papillomatosis (JP).Recent advances in mammary ductoscopy (MD) have raised new possibilities in the diagnosis and treatment of breast papillomas. This technique represents an important diagnostic adjunct in patients with pathological nipple discharge (PND) by allowing direct visualisation and biopsy of intraductal lesions and guiding duct excision surgery.Treatment of breast papillomas often entails surgical duct excision for symptomatic relief and histopathological examination. Recently, more conservative approach has been adapted. MD-assisted microdochectomy should be considered the procedure of choice for a papilloma-related single duct discharge. Furthermore, there is increasing evidence that MD has the potential to reduce the number of duct excision procedures and minimise the extent of surgical resection. Imaging-guided vacuum-assisted core biopsy can be diagnostic and therapeutic for papillomas seen on mammography and/or ultrasound.Patients with multiple papillomas do have an increased risk of developing cancer and should be kept under annual review with regular mammography  if treated conservatively. Magnetic resonance (MR) can be also used in surveillance in view of its high sensitivity. Because the risk is small, long term and affects both breasts, long-term follow-up is more appropriate than prophylactic mastectomy. Patients who prove to have solitary duct papilloma have insufficient increase in the risk of subsequent malignancy to justify routine follow-up. Breast papillomas are a variety of lesions in the breast that are characterized by a papillary configuration on gross or microscopic examination (or both). Papillomas consist of a few broad fronds, abundant stroma, and an epithelium containing both luminal and myoepithelial cells . These iMultiple intraductal papillomas occur in approximately 10% of cases of intraductal papillomas. Compared to solitary intraductal papillomas, multiple intraductal papillomas tend to occur in the younger patients, are less often associated with nipple discharge, more frequently peripheral, and more often bilateral. Essentially, these lesions appear to be susceptible to the development of carcinoma  reportedPapillomatosis is a term used to describe microscopic foci of intraductal hyperplasia that have papillary architecture and are, therefore included by Dupont and Page in the category of proliferative lesions without atypia . JP is aIntraductal papillary lesions of the breast continue to be one of the most difficult diagnostic and therapeutic problems for the surgeon as they may be histologically benign, borderline, or malignant. Subsequent surgical treatment depends largely on the histological appearance of the lesion.In patients with PND who do not exhibit palpable tumours, the localization of intraductal papilloma should be confirmed by localizing the orifice of the affected duct on the surface of the nipple and applying pressure with the fingertip to the circumference of the areola. The secretion of serous or bloody nipple discharge does not distinguish intraductal papilloma from cancer . When a Simple mammography should be performed in all patients complaining of bloody or serous PND before ductography especially if they are aged 35 years or over . IntraduDuctography is a safe, simple technique for the visualization of the affected duct system in patients with PND. Intraductal papilloma may be demonstrated by filling defects within dilated ducts. Solitary papilloma is usually observed in the collecting ducts, while multiple papillomas are frequently observed in the branching ducts in a segmental or sub-segmental distribution leading in some cases to cystic dilatation of the ductal system. Distortion, narrowing or obstruction of the ducts may indicate the presence of malignancy. Ductography, however, is a painful procedure and has considerable limitations in detecting lesions that do not completely obstruct the ductal lumen, and also in detecting multiple lesions in the same duct . TherefoWhen the physical examination reveals a palpable abnormality in a localized area of the breast, ultrasonography may be useful in determining its characteristics; whether it is a cyst, an intracystic growth or a solid tumour. Modern high-resolution ultrasound techniques with 3-dimensional views  are helpAlthough magnetic resonance imaging (MRI) seems to be superior to both mammography and ultrasound for screening young women who are at high risk of developing breast cancer, its role in the management of papillomas is currently limited -24. IntrMore recently, MR-galactography has been shown to be of diagnostic value .Nipple discharge obtained by squeezing the nipple should be examined by means of papanicolaou or May-Giemsa staining in all patients. Cytology smears of the discharge material provide information about normality, atypia and malignancy and also about papillary formation of the exfoliated cells. Tests such as Hemoccult help to detect occult blood in the secreted fluid. Modern immunological tests can be performed on cytology smears where occurrence of high levels of carcinoembryonic antigen could indicate a latent malignancy . Intraduet al described new mini-endoscope with 0.55 mm external diameter [Mammary ductoscopy (MD) is a new endoscopic technique that has been evolving over the last 15 years ,28-30. Tdiameter . InserteThese scopes also provide working channels for insufflation, irrigation, ductal lavage, and possible therapeutic intervention . The shaMD offers the advantages of accurate localisation of pathology, ductal lavage under direct visualization, and intra-operative guidance especially for lesions deep within the ductal system . In addiDespite these potential benefits of MD in the management of papillomas, this new technique is still not widely used in clinical practice due to the high cost and limited expertise. This position is likely to change in the near future.Deciding on the appropriate surgery for intraductal papilloma is problematic due to the difficulty in discriminating between intraductal papilloma and breast cancer. Moreover, the significance of intraductal papilloma as a pre-cancerous lesion is controversial to surgeons. Patients with multiple papillomas do have an increased risk of developing breast cancer and should be kept under annual review with regular digital mammography if treated conservatively. In view of the high sensitivity of MRI, the absence of enhancement typical of malignancy in women with multiple papillomas can be reassuring and supportive of conservative management . BecauseFrom a historical perspective the philosophy of management of serous or sero-sanguineous nipple discharge changed radically in the last 50 years. Opinion regarding the likelihood of it being due to cancer was sharply divided early in the last century. Judd,  in 1917,However, in the last 30 years, a more conservative approach has become accepted, resulting particularly from the studies of Haagensen in the USA and Atkins and Wolff  in the UMD has recently revolutionised the management of PND and breast papillomas. The only reliable way to both establish the diagnosis and control the discharge is ductal excision, the success of which is dependant on identifying the correct origin of the discharge. When a specific duct cannot be identified then blind excision of the retro-areolar ductal system is usually performed. MD offers the advantages of accurate localisation of pathology, ductal lavage under direct visualization figure , and intSimple light trans-illumination through the skin during MD can be used to guide duct excision. We have recently described a new technique involving ductoscopy and the use of a blue dye to perform microdochectomy . The proDietz et al  reportedNevertheless, MD has recognised limitations. MD examines 1 – 2 ducts per breast and leaves the remaining 13 – 18 ducts that open at or just below the nipple surface unexamined. MD is also incapable of reaching the peripheral small branches of the ducts due to the scopes' diameter ,30. ThusIf the papilloma is detectable on mammography and/or ultrasonography, then imaging-guided vacuum-assisted biopsy can be both diagnostic and curative Figure .Dennis et al evaluated the role of imaging-guided vacuum-assisted core biopsy as a minimally invasive method of obtaining a satisfactory diagnosis and eliminating the bothersome symptoms in patients presenting with nipple discharge. This study concluded that this technique allows safe and accurate tissue analysis and a high probability of terminating the symptomatic nipple discharge .Finally if the discharge is not troublesome and all investigations show no evidence of malignancy, then the discharge can be managed conservatively with no need for surgical intervention.Figure Current biopsy tools used with MD need further evaluation and validation, as the challenge of verifying endoscopic appearances with a histological diagnosis has not yet been overcome. The future development of reliable intraductal biopsy tools capable of obtaining tissue sample under direct visualisation sufficient for histological diagnosis can enhance further the role of MD in the management of PND and papillomas. The potential therapeutic role of MD-guided intraductal biopsy  requiresMoreover, the addition of radiofrequency  to MD asCAD: Computer-aided detectionDCIS: Ductal Carcinoma In-situJP: Juvenile PapillomatosisMCC: Micro-calcificationsMD: Mammary DuctoscopyMRI: Magnetic Resonance ImagingPND: Pathological Nipple Discharge


Spontaneous germ cell death by apoptosis occurs during normal spermatogenesis in mammals and is thought to play a role in the physiological mechanism limiting the clonal expansion of such cell population in the male gonad. In the prepubertal rat testis, the most conspicuous dying cells are pachytene spermatocytes, which are also the primary target of the apoptosis experimentally induced by the methoxyacetic acid (MAA). Since we have recently reported that Sertoli cells, the somatic component of the seminiferous epithelium, regulate not only germ cell viability and differentiation but also their death, we have further investigated the mechanism involved in such a control.In this paper we have used the protein clusterin, produced by Sertoli cells and associated with tissue damage or injury, as indicator of germ cell apoptosis in rat seminiferous tubules treated with MAA in the presence or in the absence of omega-agatoxin, a specific inhibitor of P/Q type voltage-operated calcium channels (VOCC's). We performed both a qualitative analysis of clusterin content and germ cell apoptosis by immunofluorescence experiments and a quantitative analysis by in situ end labelling of apoptotic germ cells followed by flow cytometry. The results obtained demonstrate that Sertoli cells modulate germ cell apoptosis induced by methoxyacetic acid also throughout the P/Q-type VOCC's. Ca++ entering the cells through VOCC's serves as second messenger of electric signalling, initiating intracellular events such as contraction, secretion, synaptic transmission, and gene expression.Spermatogenesis in mammals is a complex process dependent upon the hormonal stimulation as well as the dynamic interactions between the Sertoli cells, the somatic component of the seminiferous epithelium, and the germ cells. In fact, in the mammalian testis germ cells, differentiating from spermatogonia to mature spermatozoa, are in close contact with Sertoli cells which supply the nutrients and the hormonal signals essential for successful spermatogenesis. Spontaneous death of germ cells occurs normally during spermatogenesis by the process of apoptosis , leading++ influx in rat Sertoli cells [++]i raise in Sertoli cells and in Sertoli cell secretory process  in the culture medium [The previous identification of P/Q channels on the plasma membrane of Sertoli cells in the zone adjacent to the basal lamina and their involvement in the modulation of protein secretion , suggeste medium . In the The decrease of intracytoplasmic Sertoli cell clusterin and the inhibition of its accumulation into pachytene spermatocytes, following P/Q channels block, suggest that calcium channels control germ cell apoptosis throughout an indirect mechanism. The protective effect of calcium channel blockers against MAA-induced spermatocyte apoptosis is probably mediated by the inhibition of clusterin transfer from Sertoli cells to germ cells. This hypothesis agrees with recent data from literature which demonstrate that the intracellular form of clusterin could be cytotoxic -34. Clus++ channels attenuates neuronal apoptosis while the block of N- and P/Q type channels has no effect [Furthermore, in this paper we demonstrate a role of P/Q-type VOCC's specific for the control of male germ cell death. In other cell types, i.e. cultured cortical neurons, exposed to amyloid β protein in order to induce apoptosis, the block of L-type voltage-sensitive Cao effect .Our work confirm and extend previous data showing that the VOCC's localized exclusively on Sertoli cell plasma membrane modulate Sertoli cell response to injuries that could damage germ cell differentiation. Such intratesticular regulatory mechanism controlling germ cell apoptosis adds a further piece of the puzzle concerning the knowledge of the apoptotic program in the testis .FB was responsible for experimental activity. She performed cell cultures, immunofluorescence and flow cytometry analysis, partecipated in the analysis of data and in drafting the manuscript. SA collaborated in the immunofluorescence analysis of seminiferous tubule cryosections and provided valuable suggestions during writing the manuscript. AD was responsible for design and coordination of the study. She analyzed the data and drafted the manuscript. All authors read and approved the final manuscript.


PrP gene polymorphisms. To test the hypothetical linkage between PrP gene expression and genetic susceptibility, PrP mRNA levels were measured by real-time RT-PCR in six ovine tissues of animals with different genotypes.Cellular prion protein expression is essential for the development of transmissible spongiform encephalopathies (TSEs), and in sheep, genetic susceptibility to scrapie has been associated to PrP gene expression analysis the stability of several housekeeping (HK) genes was assessed in order to select the best ones for relative quantification. The normalisation of gene expression was carried out using a minimum of three HK genes in order to detect small expression differences more accurately than using a single control gene. The expression stability analysis of six HK genes showed a large tissue-associated variation reflecting the existence of tissue-specific factors. Thereby, a specific set of HK genes was required for an accurate normalisation of the PrP gene expression within each tissue. Statistical differences in the normalised PrP mRNA levels were found among the tissues, obtaining the highest expression level in obex, followed by ileum, lymph node, spleen, cerebellum and cerebrum. A tendency towards increased PrP mRNA levels and genetic susceptibility was observed in central nervous system. However, the results did not support the hypothesis that PrP mRNA levels vary between genotypes.Previous to the PrP gene expression presented here provide valuable baseline data for future studies on scrapie pathogenesis. On the other hand, the results on stability data of several HK genes reported in this study could prove very useful in other gene expression studies carried out in these relevant ovine tissues.The results on  The norPrP gene (nPrP) was calculated as the ratio between the Q values of PrP gene amplification and the NF calculated for each sample.Finally, the normalised expression level of the -1) as recommended for use of parametric tests on relative data. Then nPrP values along with all available independent variables  and their interactions were submitted to the GLM procedure of SAS statistical package version 8 . This analysis showed that sex and age had no significant effects and therefore, only tissue and genetic susceptibility and their interactions as independent variables for effects on nPrP were included in the final model. Genetic susceptibility was considered as risk levels [In order to compare among tissues, analysis of variance of the reference values (NF) was carried out with the GLM procedure of the SAS statistical package version 8 . Once the results of this model showed no significant differences among tissues, the PrP/NF ratios (nPrP) were transformed according to the formula arc sin √ (nPrPx100k levels . CompariThe author(s) declare that they have no competing interests.DG carried out the design of the study, the experimental work and drafting of the manuscript. RJ performed the statistical analysis and participated in the critical reading of the publication. AH participated in the design and coordination of the study and drafting of the manuscript. All authors read and approved the final manuscript.


In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group.Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes.The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome. HoweverChromatin landscape of a region plays a major role in determining and modulating the expression status of its neighbouring genes . The rolcis-regulatory regions of genes further demonstrates their role in transcriptional regulation . t-test for the number of repeats and the repeat content in terms of length in base pairs in each sequence set  content, SINES and genes with short introns . Eisenbein-silico observations and strengthens the domain concept for concerted expression of clustered genes. The role of nucleosome formation potential is apparent from the present analysis in both the housekeeping genes as well as tissue specific genes but with an opposing correlation. Housekeeping genes apparently discourage nucleosome formation to match their expression profile in space and time by ensuring accessibility to transcription machinery. In addition, they also show a significant enrichment in poly (dA.dT) stretches, which are known to destabilise nucleosomes. On the other hand, the tissue specific genes show higher scores for nucleosome formation potential through which they perhaps provide selective accessibility to the transcriptional machinery. Further, our analysis suggests that tissue specific genes resort to additional global regulatory features such as matrix association, which would facilitate maintenance of functionally distinct domains to insulate themselves from both silencing and activating regulatory influence of adjacent domains. The differential distribution of repetitive sequences in housekeeping and tissue specific genes might also play an important role in maintaining distinct chromatin landscape over these regions.The paradigm for regulation of gene expression in human tissues has shifted the focus from involvement of a battery of transcription regulators to global regulatory mechanisms . These mWe have demonstrated that the regulatory regions of housekeeping and tissue specific genes have differential chromatin architecture with respect to S/MAR binding, nucleosome positioning potential and repetitive sequences. This has potential implications for regulation of gene expression in eukaryotic genomes.[In this study, the 5' and 3' flanking regions of genes were analysed for various attributes of chromatin organisation. The list of human housekeeping genes (Hkg) was retrieved from ,36. 532 MAR Finder was used for prediction of S/MAR regions ,38. All 2–5 using in-house programs. Recon was used for evaluating nucleosome formation potential in the sequences [The upstream regions 2000 bp) were scanned for nucleosome exclusion elements ,20 – pol00 bp werequences . The scoThe Recon scores at 400 bp were used to draw correlation between the nucleosome formation potential and expression levels in the two sets of genes. In each sequence set, genes with expression levels <500 and >5000 affymetrix expression units were classified as low and high expression genes respectively. We considered a minimum ten fold difference in the expression levels of genes as a relevant criterion for classifying them as high and low expression genes. In Hkg, this criterion yielded 33 low expression and 35 high expression genes. In Tsg, we categorised 416 low expression genes and 24 high expression genes.RepeatMasker version: 20040306-web was used to calculate the repeat content in 2000 bp upstream sequences of the two groups of genes .S/MAR: scaffold/matrix attachment regionsHkg: housekeeping genesTsg: tissue specific genesdf: degree of freedomMG, VB and SKB contributed to the study design, analyses and in drafting the manuscript. MG, PS, SKDS, DD, KK and GP were involved in the data retrieval and analyses. All authors read and approved the final manuscript.gene list and expression levels of housekeeping genes, gene list and expression levels of tissue specific genes. 'supplementaryfile1.xls' contains the list of housekeeping and tissue specific genes and their expression levels used for the analysis.Click here for file


Accurate tools for assessing household wealth are essential for many health studies in developing countries. Household survey and participatory wealth ranking (PWR) are two approaches to generate data for this purpose.A household survey and PWR were conducted among eight villages in rural South Africa. We developed three indicators of household wealth using the data. One indicator used PWR data only, one used principal components analysis to combine data from the survey, while the final indicator used survey data combined in a manner informed by the PWR. We assessed internal consistency of the indices and assessed their level of agreement in ranking household wealth.Food security, asset ownership, housing quality and employment were important indicators of household wealth. PWR, consisting of three independent rankings of 9671 households, showed a high level of internal consistency . Data on 1429 households were available from all three techniques. There was moderate agreement in ranking households into wealth tertiles between the two indicators based on survey data , but only limited agreement between these techniques and the PWR data .Both PWR and household survey can provide a rapid assessment of household wealth. Each technique had strengths and weaknesses. Reasons for differences might include data inaccuracies or limitations in the methods by which information was weighted. Alternatively, the techniques may measure different things. More research is needed to increase the validity of measures of socioeconomic position used in health studies in developing countries. Research into the socioeconomic determinants of health requires accurate tools for assessing socioeconomic position. While in developed countries pre-existing data are often available, these resources rarely exist in developing countries and original data must be collected . EconomiA variety of proxy measures of socioeconomic position have been developed. These have included shortened income or expenditure questionnaires, and measures of housing quality, education or nutritional status  RecentlyAn alternative technique is to use participatory wealth ranking (PWR), in which community members rank the wealth of households in their community. This approach is widely used in development practice , but rarWe conducted a household survey and PWR in rural South Africa. We constructed three indicators of household wealth, using the data from each of the two techniques separately and also by combining them. We assessed internal validity where this was possible, assessed agreement between the results of the techniques in their ranking of household wealth, and investigated the reasons for any differences.The study was conducted in eight rural villages of Limpopo Province, South Africa. The province is among the most deprived in the country, with nearly 50% of the population under 15 years old, unemployment in excess of 40%, and high levels of labour migration -20. The PWR was conducted in the local language by specialised facilitators from a local development NGO . Data were recorded on pre-designed data collection forms ,23.general statements". Households were then ranked from the poorest to the wealthiest according to these definitions and piles of households of comparable wealth generated. Participants were then asked to describe the characteristics of the households in each ranking pile ("pile statements"). Neither the number of wealth ranks nor the number of households in each rank was determined in advance, although at least four separate piles had to be generated during the process.Community members residing in the same village section, most often women from poor households, drew a map of their residential area and listed the households on cards. Following this, groups of 4–6 residents were asked to characterise households that were "very poor", "poor, but a bit better off", and "doing OK". The proceedings of this discussion were captured by the facilitator in the form of "The ranking process was then repeated twice more with different groups of four to six community members, so that statements were collected and each household ranked on three separate occasions.A random sample of approximately 200 dwellings from each village  was visited at least three times where necessary to collect data. Interviews were conducted in the local language. Interviewers received extensive training and data entry was validated through data cleaning procedures. Questionnaires captured salient aspects of socioeconomic well-being including household members' education and employment status, details of the dwelling construction, ownership of a small number of assets, details of the most important household incomes and information on food security.Three approaches were used to generate a measure of relative household wealth. The first used data only from the participatory wealth ranking; the second used data from the household survey, but with their selection and weighting informed by PWR; the third used only data from the survey, employing principal components analysis (PCA) to determine the weights.Score for pile n = 100*((N-n)/(N-1)), where n was the pile number and N was the total number of ranking piles.Details of the scoring method used are provided in detail elsewhere . Brieflypile statements made in relation to the piles generated were assigned the numeric score allocated to the pile. An average pile statement score was calculated as the mean of the pile scores to which that statement was associated, covering the full PWR process in all eight villages  and a minimum score of -10 (poorest).Survey data were used to generate an indicator of household wealth, using PWR to inform which factors to use and how to weight the data. Where data were available on aspects of household wealth relating to each of the 10 commonest themes identified in PWR, this was used to inform the calculation of the index of household wealth Table . Broadlya priori following literature review and piloting in the local area, were made available for entry into the PCA. Items included were not limited to durable assets [Fourteen variables capturing salient aspects of household wealth, decided upon e assets  (Table 32-test (p < 0.05) were not included in the PCA (percentage of household members of working adult age and land tenure). The remaining factors were included. PCA transforms a set of correlated variables into a set of uncorrelated 'components'. When variables hold information about some underlying concept, PCA can produce the best single composite variable among all possible linear functions of the original variables [Two factors not associated in the expected direction with the value of selected non-livestock assets per person (screening variable) in a χariables . The comA number of analyses were run. Factors with component loadings less than 0.2 on the first principal component were excluded . Nine factors were included in the final analysis in which the first principal component explained 22.7% of the variance of the factors in the model. The greatest weight was given to the density of household living conditions (scoring coefficient = 0.44), with the value of non-livestock assets (0.42) and the food security indicator (0.39) also being important. The lowest weighting was given to the proportion of individuals receiving an income (0.23). A wealth index was calculated for households where data were available on all variables. This component was normally distributed and had a mean of 0 and a standard deviation of 1.For the PWR method only, the intra-cluster correlation coefficient, a measure of internal consistency, was first calculated from a random-effects ANOVA to describe the level of agreement in rankings of wealth between each of the three rankings made for each household .2-test.Secondly, the association of each index with the individual survey indicators was estimated. Households were divided into wealth-rank tertiles on the basis of each of the methods. The association between these tertiles of wealth and each specific indicator of wealth from the survey was assessed using a χFinally, the three techniques were compared in their ranking of household wealth. The agreement of each technique placing households into wealth tertiles was estimated with a kappa coefficient. Spearman rank correlation coefficients were also calculated. While correlation coefficients measure the level of predictability of one variable on the basis of another, they do not directly assess agreement; thus a correlation coefficient of 1 will be measured if all values of one variable are twice that of another, though these clearly do not agree.general statements were coded describing the general properties of households seen as "very poor" (1240), "poor, but a bit better off" (1097) or "doing OK" (1216). A further 8856 pile statements were coded, describing the characteristics of the households included in each of the piles assembled by the wealth ranking process. Some 47 statements were made more than 15 times in both stages of the process . Some 3556 Households judged "very poor" by PWR participants were struggling to feed themselves and to clothe or educate their children, with little access to jobs or housing Table . HousehoSurvey data Table  suggesteThe single-measure intra-class correlation coefficient from a random effects two-way ANOVA on the three rankings of household wealth, over 9671 households, was 0.81 (95%CI0.79–0.82) denoting a high level of agreement.Data on individual socioeconomic variables were significantly correlated (p < 0.01) with each of the wealth indices in most cases Table . Land teThe survey data methods were quite strongly correlated , and there was a reasonable degree of agreement in their placing of households into wealth-rank tertiles (Kappa = 0.43).The PWR wealth index was significantly, but weakly, correlated with both the index combining PWR and survey information  and the PCA-based method . The levels of agreement in placing households into wealth tertiles were low (kappa statistics of 0.20 and 0.17 respectively).We constructed three indices of household wealth using data from a household survey and participatory wealth ranking. PWR and the survey identified similar dimensions of socioeconomic well-being as important. The two indices developed from survey data showed a reasonable level of agreement in ranking households into wealth tertiles. However, there was limited agreement between the survey-data based indices and the index based only on information from PWR. Methodological differences meant that it was not surprising that the methods differed in their results, though the magnitude of the differences noted was surprising.The three approaches differed in at least two dimensions. The first dimension was whether information was provided by household members (as for both of the techniques using survey data), or by other community members (for the PWR only approach). The second dimension was whether community views were used to weight the importance of different aspects of wealth (as for the approaches that used PWR data), or whether external statistical rules were used (as in the PCA method). Nevertheless, there were striking similarities in the associations seen between the three wealth indices and each of the survey variables collected. The strongest associations between individual variables and the PWR wealth index were seen for variables associated at a significance level of p < 0.001 with both survey indices, while weaker associations also generally mapped across all three indices. The only exceptions to this were with the variables on household electrification and water supply.Despite these similarities, the PWR index showed relatively low agreement with the survey-based measures, even when themes from the PWR were used to inform the selection and weighting of data. Two potential reasons for the lack of agreement are; firstly, each may have suffered from inaccurate data collection or weighting; secondly, the techniques may measure different things.The survey attempted to maximise accurate reporting through collecting data on objective indicators, fieldworker training and stressing the importance of honesty to participants. Nevertheless, reporting biases may have occurred . PWR parSurvey data included information on employment, educational status and asset-ownership of migrants, since temporary migrants are important contributors to the rural economy in South Africa -30. HoweEach method might have weighted the importance of different aspects of household wealth differently. PCA assigns weights to variables according to mathematical rules, while wealth ranking participants assess households in ways that are complex and non-transparent. Our approach to PCA incorporated different facets of wealth, as in previous applications,  and drewSepedi, applying a translation of the question, "What are the characteristics of a very poor household?" to start the ranking process. Many characteristics identified by PWR participants resonated with the survey data. Nevertheless, the way in which PWR participants judge household wealth was inevitably unclear. One possibility is that PWR participants may have ranked households more directly on their current level of welfare than the survey based methods.Finally, there was also room for differences in interpretation in PWR. Wealth ranking was conducted in In our comparison of three approaches to assessing household wealth, the method by which data were collected was more important than the method by which variables were selected or weighted in determining agreement between the rankings. None of the techniques was precise in defining what aspects of wealth they wished to measure, so ultimately the indices may have measured different things. Survey data on individual variables may be most appropriate when comparison is needed between different settings or time-periods. PCA is a useful tool for the reduction of multiple indicator data, yet in this application did not agree with household wealth ranking ascribed by community members. PWR allowed a measure of wealth to be generated for about 200 households in a given geographical area over a two-day period by a skilled practitioner. Although the use of this technique will require epidemiologists to attain new skills, PWR may represent a rapid, useful and internally valid tool for health researchers in situations where locally-grounded data on household wealth are required.The author(s) declare that they have no competing interests.


Past clinical trials of antimicrobial treatment in soft tissue infections have focused on non-standardized clinical and physiological outcome variables, and have not considered the subjective experience of patients. The objective of this study was to develop a health-related quality of life questionnaire (HRQL) for patients with extremity soft tissue infections (ESTI) for future use in clinical trials.The design of this study followed published guidelines and included item generation, item reduction, and questionnaire preparation. Study subjects were consenting English-speaking adults with acute ESTI requiring prescription of at least two days of outpatient intravenous antibiotic therapy.A list of 49 items that adversely impact the quality of life of patients with ESTI was generated by literature review, informal health professional feedback, and semi-structured interviews with twenty patients. A listing of these items was then administered to 95 patients to determine their relative importance on quality of life. A questionnaire was prepared that included the twenty most important items with a 5-point Likert scale response. Questionnaire domains included physical symptoms, problems performing their activities of daily living, impairment of their emotional functioning, and difficulties in their social interactions as related to their ESTI. The final questionnaire was pre-tested on a further ten patients and was named the ESTI-Score.The ESTI-Score is a novel instrument designed to quantify the impact of ESTI on quality of life. Future study is required to determine its validity and responsiveness before use as an outcome measure in clinical trials. Soft tissue infections (STI) are among the most common infectious diseases requiring antibiotic treatment ,2. DespiThe use of Health Related Quality of Life (HRQL) scales have been developed and demonstrated to be useful and valid primary outcome measures in clinical trials in a number of diseases not limited to asthma, rhinoconjunctivitis, polycystic ovarian syndrome, and sleep apnea -8. AlthoThe study methodology followed previously published guidelines for development of HRQL instruments ,12. ThisPatients with ESTI were enrolled from the Home Parenteral Therapy Program (HPTP) clinic at the Peter Lougheed Centre, Calgary, Alberta, Canada . The HPTThe goal of this phase was to identify all possible items that might adversely impact the quality of life of patients with ESTI. These items were identified using four standard methods: 1) a review of the published literature on the clinical features of soft tissue infections, 2) a review of HRQL scales in other medical conditions, 3) semi-structured interviews with a group of patients, and 4) the collective experience of the study investigators and clinic staff. The patient interviews were performed by trained research nurses and took approximately 30 minutes. The interview used open-ended questions to identify all possible areas of dysfunction  that might be adversely affected by their ESTI.The purpose of this phase was to identify the most important items for patients with ESTI. Study participants independently completed a questionnaire containing the items identified in the item generation phase. They were asked to identify which of the items were problems for them. For items identified as being a problem, they were asked to rate how important it was on a 5-point Likert scale . The overall importance of each item was determined by calculating its frequency importance product (FIP). This was done by multiplying the frequency that a particular item was reported as a problem by the mean importance assigned to it .The twenty items with the highest FIPs were incorporated into the final questionnaire. It was pre-tested on another group of consenting patients to ensure that it was free of grammatical errors and that individual items and the overall format were easily understood.a priori to be 20 patients for item generation and 100 patients for item reduction based on the guidelines of Kirshner and Guyatt . One patient was subsequently excluded because he was recognized later to be seventeen years of age at the time of enrollment. One patient was inadvertently enrolled into the study on two separate occasions and as such only the first presentation was analyzed.The characteristics of the 95 analyzed patients and their infections are summarized in Table The overall importance of each of the items was calculated as frequency-importance-products and reported in Table The twenty highest ranked items identified in item reduction Table  were gropost hoc calculated for each of the patients in the item reduction cohort. The mean ESTI-Score was 47.2 ± 21.1 points and their distribution is shown in Figure The final ESTI-Score for a patient was calculated by adding their scores for each item. The minimum and maximum possible scores are zero and one hundred respectively. The ESTI-Score was post hoc analysis, of our patient cohort, the ESTI-Score produced a broad range of near-normally distributed values, potentially reflecting the range of severity of ESTI in our patients.We report the development of the first HRQL indicator for use in patients with ESTI. This tool was developed using established methodological guidelines and included a diverse cohort of ambulatory adult patients with a variety of soft tissue infections. It incorporated items representing multiple areas of quality of life impairment including physical symptoms, activities of daily living, emotional and social functioning. When pre-tested on another group of patients the final questionnaire was found to be straightforward and easy to independently complete in less than 10 minutes. In a Clinical trials of ESTI reported to date have largely used a variety of disease-oriented outcome measures. Often a categorical assessment such as "cure" or "failure", "resolution of infection", or "improvement" is assigned by a study investigator based on a non-standardized clinical assessment -22. AnotGeneric health measures such as the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) , and theAs a result of the ESTI-Score being developed using a cohort of patients, it does have face and content validity. However, there are a number of limitations of the current study. First, it requires further prospective assessment in another cohort of ESTI patients prior to being used as a primary outcome measure in clinical trials. Areas to be assessed include its reproducibility in patients with a stable disease state, its responsiveness to changes in infection severity, and its relationship to other markers of disease severity. Second, the ESTI-Score was derived from a group of North American adult patients receiving parenteral antibiotics at a single outpatient parenteral therapy clinic. Patients with mild disease were excluded based on the requirement for at least two days of parenteral therapy and only English speaking patients were studied. Whether it will be generalizable to adult patients in other outpatient settings in other regions remains to be seen. Third, while ESTI may have subsequent chronic impairment on quality of life, they typically are acute conditions that resolve over weeks or months and in most cases will not have a major effect on an individual's quality of life during their lifetime. The ESTI-Score may therefore represent more of an acute comprehensive disease severity index than a traditional measure of quality of life.We report the development of the ESTI-Score that is designed to quantify patients subjective experiences associated with having an ESTI. Future studies are needed to validate this HRQL instrument in another cohort of adult ESTI patients so that it may be used as an important outcome measure in future clinical trials evaluating management strategies for ESTI.Extremity Soft Tissue Infections (ESTI)Frequency importance product (FIP)Health-Related Quality of Life Questionnaire (HRQL)Home Parenteral Therapy Program (HPTP)Interquartile range (IQR)Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)Nottingham Health Profile (NHP)Soft tissue infections (STI)None of the authors have personal, professional, or financial conflicts of interest that would influence the conduct or reporting of this study.AJS collected data, analyzed results, and drafted the manuscript. KL conceived and designed the study, enrolled patients, analyzed data, and contributed to the manuscript drafting. RRR, MWM, JMG, DN, and TJL enrolled patients and collected data. All authors contributed to revision of and approval of the final manuscript.The pre-publication history for this paper can be accessed here:


Nearly 20,000 patients per year in the UK receive total knee arthroplasty (TKA). One of the problems faced by the health services of many developed countries is the length of time patients spend waiting for elective treatment. We therefore report the results of a study in which the Salisbury Priority Scoring System (SPSS) was used by both the surgeon and their patients to ascertain whether there were differences between the surgeon generated and patient generated Salisbury Priority Scores.The Salisbury Priority Scoring System (SPSS) was used to assign relative priority to patients with knee osteoarthritis as part of a randomised controlled trial comparing the standard medial parapatellar approach versus the sub-vastus approach in TKA. The operating surgeons and each patient completed the SPSS at the same pre-assessment clinic. The SPSS assesses four criteria, namely progression of disease, pain or distress, disability or dependence on others, and loss of usual occupation. Crosstabs and agreement measures (Cohen's kappa) were performed.Overall, the four SPSS criteria showed a kappa value of 0.526, 0.796, 0.813, and 0.820, respectively, showing moderate to very good agreement between the patient and the operating consultant. Male patients showed better agreement than female patients.The Salisbury Priority Scoring System is a good means of assessing patients' needs in relation to elective surgery, with high agreement between the patient and the operating surgeon. Nearly 20,000 patients per year in the UK receive total knee arthroplasty (TKA) at an estimated annual cost of 70 million pounds. Patients who undergo knee surgery are affected by their condition on a very personal basis in terms of disability. For athletes at the prime of their career, not being able to perform at an optimal level competitively is a major disability. In comparison, an elderly patient with knee osteoarthritis may find simple activities such as walking to be a disability .One of the problems faced by the health services of many developed countries is the length of time patients spend waiting for elective treatment. Despite various efforts, waiting lists on the United Kingdom National Health Service (NHS) remain long, with the various clinical specialities having different waiting times for elective treatment . The focRating systems should provide an objective assessment of any given subject so that direct comparison can be made with other examples of the same condition . A totalA randomised controlled trial, the SMAK Arthroplasty trial, compared the effectiveness and efficiency of a standard medial parapatellar approach versus a sub-vastus approach in TKA and evaluated clinical outcomes of care in each group. Patients undergoing primary bi- or tri- compartmental knee replacement for any indications were recruited from the University Hospital of North Staffordshire. Ethical approval was obtained from the local ethics committee for the trial.Patients were recruited at their pre-operative assessment, with randomisation taking place on the day of admission for surgery. Only patients who required unilateral knee replacement who had given their informed consent to take part in the study were eligible to take part in the trial. The operating surgeon also had to have no clear preference for either of the approaches. Patients not eligible to enter the trial were those who needed revision knee replacement, bilateral knee replacement, required major arthrotomy in the other knee within a 12 month period, had previous open surgery in or around the knee over the last 12 months, or had a valgus angle greater than 20°.As part of this trial, the operating surgeon and the patient completed the Salisbury Priority Scoring System (SPSS) (see figure K) values were obtained to measure the agreement between the two sets of data.All 230 patients recruited for the trial and the clinicians performing the procedure completed the SPSS at the pre-assessment clinic. The research nurse involved in the SMAK arthroplasty trial facilitated both groups in filling out the questionnaire separately. Analyses of quantitative results were undertaken using the Statistical Package for Social Sciences (SPSS Manager 12.0 for Windows). Crosstabs was performed to compare the agreement between clinicians and patients. Cohen's kappa  declare that they have no competing interests.All authors contributed equally to this work. NM is the corresponding author. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Although referring patients to community services is important for optimum continuity of care, referrals between hospital and community sectors are often problematic. Nurses are well positioned to inform patients about referral resources. The objective of this study is to describe the impact of implementing six nursing best practice guidelines (BPGs) on nurses' familiarity with patient referral resources and referral practices.A prospective before and after design was used. For each BPG topic, referral resources were identified. Information about these resources was presented at education sessions for nurses. Pre- and post-questionnaires were completed by a random sample of 257 nurses at 7 hospitals, 2 home visiting nursing services and 1 public health unit. Average response rates for pre- and post-implementation questionnaires were 71% and 54.2%, respectively. Chart audits were completed for three BPGs (n = 421 pre- and 332 post-implementation). Post-hospital discharge patient interviews were conducted for four BPGs (n = 152 pre- and 124 post-implementation).There were statistically significant increases in nurses' familiarity with resources for all BPGs, and self-reported referrals to specific services for three guidelines. Higher rates of referrals were observed for services that were part of the organization where the nurses worked. There was almost a complete lack of referrals to Internet sources. No significant differences between pre- and post-implementation referrals rates were observed in the chart documentation or in patients' reports of referrals.Implementing nursing BPGs, which included recommendations on patient referrals produced mixed results. Nurses' familiarity with referral resources does not necessarily change their referral practices. Nurses can play a vital role in initiating and supporting appropriate patient referrals. BPGs should include specific recommendations on effective referral processes and this information should be tailored to the community setting where implementation is taking place. The provision of continuous, comprehensive client care is critical in today's complex health care system where clients experience shorter hospital stays, and move quickly from one care setting to another. Continuity of care is an essential feature of a well-functioning health care system. It is demarcated by coherent and linked services and results from "good information flow, good interpersonal skills, and good coordination of care" . AchieviThe referral process is a systematic approach to help clients use services or resources, with the aims of promoting wellness, and enhancing self-care and quality of care . There iA limited number of studies -10 have Recommendations for appropriate and timely referrals are included in many clinical practice guidelines -13. WhilThe Registered Nurses' Association of Ontario has been developing and implementing nursing best practice guidelines in the province of Ontario, Canada since 2001 . Our teaThe BPG implementation process is described in detail elsewhere . The guiHealth care organizations in Ontario were invited to participate in the implementation of a BPG through a request for proposals process. The implementing organizations were selected by peer review. At each site, a clinical resource nurse (CRN) led implementation of the BPG recommendations ,18. CRNsEligibility criteria for participants were registered nurse, licensed practical nurse or health care aide; assigned to work on one of the units implementing the BPGs; and, not expected to go on maternity leave or to take an extended leave of absence from the clinical unit or from the agency during the six month period of guideline implementation. Patient eligibility criteria were developed for each BPG based on knowledge of the patient population characteristics at each site , a sequential sample of patient charts was retrieved from medical records for a period of six to eight weeks pre- and post-implementation; and, for four BPGs , patient interviews were completed by phone post-hospital discharge.A list of potential referral resources was developed for each BPG in consultation with the CRN and following a review of BPG recommendations. Specific referral resources were identified for the following: other members of the multi-disciplinary team, service provider organizations and information sources on self-management of the illness. In the pre- and post-implementation questionnaires, nurses were asked to rate their familiarity with relevant community resources on a scale of 1 to 5 , and to indicate whether or not they had referred a patient to each of these resources in the past month . Since the number of referral resources listed varied by BPG, standardized mean scores and standard deviations were calculated. For the self-reported familiarity scale, standardized scores ranged from 1 to 5. Scores for self-reported referrals ranged from 0 to 1.To assess whether patients had been given information about referral resources and whether or not they had telephoned, visited or received assistance from referral resources, patient interviews were conducted post-hospital discharge. For three of the BPGs , patients were contacted at four weeks follow hospital discharge. For breastfeeding patients, follow-up data were collected at eight weeks postpartum.For two topics, obtaining direct patient interview data post-discharge was not feasible due to either the nature of the patient population or service delivery issues. Specifically, with respect to the BPG of delirium-dementia-depression, concern was expressed about this vulnerable population as well as the complexity involved in obtaining consent from family members of participants with delirium or dementia. For the topic of venous leg ulcers, patient interviews were not feasible with the participating home visiting nursing service organization.Chart abstraction forms were developed for each of the BPGs. However, we included extraction prompts for data on referrals for only three of the BPGs due to the absence of information about referrals to community resources in the hospitals charts for the other three topics . The CRN conducted the first five to 10 pilot charts to make sure that the systems for obtaining the charts and the coding categories were feasible. Then she either trained another staff member to conduct the chart audit (delirium-dementia-depression and smoking cessation BPGs) or conducted the chart audits herself (venous leg ulcers BPG). Pilot data were included in the main findings.For chart abstraction and patient interviews, documentation of a referral being made (from patient charts), or of a patient having been given information about a referral resource or having accessed a referral resource (from patient interviews) were coded dichotomously as follows: . An average score was computed across all referral resources listed for the specific BPG.Factor analysis, using varimax rotation was undertaken for the two referral measures  assessed by the nursing questionnaires for each BPG . The KaiThe University of Ottawa health and social sciences ethics board provided ethics approval. Ethics reciprocity was requested and received from participating agencies. For the sites implementing the smoking cessation BPGs, the clinical data forms  and the data collection protocol were also reviewed by their organizational ethics review board.Response rates for nurses were calculated based on the number of nurses randomly selected to participate in the study. In the analysis, we only included the responses of nurses who completed both pre- and post-implementation questionnaires. Patient follow-up interview response rates were estimated using the number of eligible patient charts as the denominator for the initial interviews conducted with patients while they were in hospital. The purpose of these initial interviews was to determine, from the client's perspective, whether nursing care received was consistent with the BPG recommendations selected by the organization for implementation. For the second set of follow-up interviews conducted by phone post-hospital discharge, response rates were calculated using the number of in-hospital interviews as the denominator. Patients were only asked about referrals in the second set of follow-up interviews.Using paired t-tests, differences in mean scores between the pre- and post-implementation periods were compared for nurses' self-reported knowledge and referral patterns for each BPG. For the two scales with two-factor solutions, mean scores and pre- and post-implementation comparisons were computed for each factor. Pre- and post-implementation mean scores for documented patient referrals and patient's self-reports of referrals were compared using the independent student's t-test.The BPGs were implemented in seven hospitals, two home visiting nursing service organizations and one public health unit. Seventeen program units participated in the pilot , the only statistically significant increase in referrals to individual resources observed on the chart audit was to other nurse specialists .Few previous studies have examined changes in referral patterns following implementation of nursing BPGs. We assessed changes in referrals from the perspective of both nurses and patients, as well as using chart audits. The patterns of reported referrals from these information sources offer important insights regarding the BPG implementation process and continuity of care.Various factors may have influenced the uptake of referral recommendations. First, BPG recommendations for referrals are stated in rather general terms, written so as to be applicable to nurses working in various sectors of the health system. This lack of specificity may have limited their uptake. Second, content knowledge about the health issue is an important aspect of incorporating guideline recommendations into practice. For example the practice recommendations for delirium-depression-dementia in older adults require nurses to identify symptoms of delirium, dementia and depression in order to make a referral for medical diagnosis. The larger pre- versus post- intervention differences in nurses' familiarity scores relative to nurses' self-reported referrals was expected, as awareness about a referral source must precede decisions to make referrals to that source. Third, health care providers need more than knowledge to make a referral. They also need an appreciation of what services a referral source can offer before being convinced that a referral is worthwhile for the client. This was demonstrated, in part, by the pattern of referrals we noted. For three BPGs , referrals to sources that were "in-house" (i.e. offered in the institution where the nurses were employed) were more frequent than referrals to external agencies or resources. For the venous leg ulcer BPG, a significant increase in referrals to specialist nurses may indicate an increased likelihood of referrals when there is a clear horizontal referral mechanism for nurses to refer to other nurses.CRNs were attempting to implement many BPG recommendations in a relatively short time. Recommendations pertaining to referrals may not have been a consistent priority for all sites. We do not know the extent to which CRNs stressed the importance of referrals in their educational sessions. Previous research has demonstrated the importance of training nurses and other professionals on how to make referrals and how to motivate patients to actually keep referral appointments ,21. ThesOther studies have shown a marked increase in appropriate referrals when this is an explicit and primary intervention focus. For example the introduction of a program aimed at increasing referrals for asthma education of patients consulting at the emergency department for acute asthma found that the number of referrals increased more than 10-fold over four months . Each AsSeveral factors may have contributed to the differential patterns of referrals to clinical services within the agency, referral resources external to the agency and Internet sources. Referrals in-house may have led to positive feedback to the nurses on whether patients were finding the referrals helpful. In part, this may have accounted for the observation that referrals within the agency were more likely to increase than other types of referrals. Nurses may also have been more familiar with in-house referral resources and information about these referral resources may have received more emphasis during education sessions. Nurses and patients alike may not have considered suggestions to seek information on the Internet as a "referral" per se. This may have altered their responses to questions about referrals to the Internet. However, it may also reflect the computer skills of participating nurses and their lack of up-to-date information on credible Internet sites. Nurses have been found to prefer more interactional sources of knowledge compared to e-mails and the Internet . FinallyThe focus of this study was on patient referrals that were initiated following introduction of the BPG recommendations. Since making a referral often requires an inter-disciplinary approach, future inquiries should also assess changes in familiarity with referral sources and in reported referrals by other members of the interdisciplinary health care team.The type of clinical setting where BPG recommendations were implemented may also have influenced referral patterns. Some guidelines are more suited to recommending referrals that would be within nurses' scope of practice. Furthermore, the breastfeeding and smoking cessation guidelines recommend community organizations that are open to self-referrals. However, asthma, venous leg ulcers and delirium-depression-dementia BPGs have a predominance of referral recommendations with a medical focus. Thus, depending on the BPG and the setting, initiating a referral may require a physician's order. However, knowledge of referral sources, increased awareness of the value of appropriate referrals, and familiarity with the means to support patients in following up referrals may all influence effectiveness of the referral process. Differences in intra- and inter-organizational context , and diverse organizational expectations of nurses' practice (e.g. job descriptions for nurses) may have influenced referral patterns. These factors create different conditions for new referral processes to take hold. However, it is not possible to separate out the relative influence of these contextual factors on referral processes within the participating agencies in this study. Future studies should aim to examine the contribution of these factors on referral processes, thereby providing critical information on the mechanisms by which new referral processes take hold within and between agencies and further guidance on the transferability of findings.We recommend that health care agencies interested in helping their clients access community resources work collaboratively with agencies in their community to develop strong documentation systems including the use of electronic or web-based formats for referral. While identifying referral sources for inclusion in our tools, CRNs identified many community and Internet-based sources for referral that had been previously untapped by nurses in their setting. Anecdotal evidence through comments of participants indicated that better collaboration between hospital and community sectors is also needed. Prompts on the chart and a rapid web-based or email system would support systematic tracking of referral recommendations and their uptake by patients.This study examined referrals made by the same nurses prior to and following implementation of the BPGs. Although our study was prospective, there was no concurrent control group of agencies where BPGs were not being implemented. A concurrent control group would be an important addition to future studies to adjust for factors other than BPG implementation that may have changed nurses' referral patterns. In addition, future studies need to have larger numbers of patients for the measurement of longer-term referral outcomes.The timing of patient interviews may have introduced a recall bias. Response rates for patient interviews were lower than for nurses and thus, patient interview data is likely from a non-representative sample. This is especially likely for the post-implementation patient interviews for smoking cessation and diabetes BPGs. Thus, pre- and post-comparisons of patient reports of referrals should be made cautiously. There was a difference in the nurses' and patients' reports of referral patterns. Since we were not able to match patients to assigned nurses, we cannot determine whether the patients' and nurses' reports of referrals are discrepant, or whether the patients' experiences were with nurses other than those who completed the questionnaire. We did not ask nurses to indicate how many referrals they had actually made in the past month. This might have provided a better gauge of any shift in the nurses' actual referral practices.A mixed methods study would reveal further insights into what constitutes a referral from the perspectives of patients, families and nurses and how this perspective influences responses to questions about referral practices.This study contributes important new information about the impact of implementing nursing BPGs on patient referrals. While nurses' familiarity with referral resources increased significantly for all six BPGs; referrals made by nurses based on their self-reports, data on patient charts and interviews with patients indicated mixed results. Referrals to Internet resources were minimal.Nurses roles in initiating and supporting appropriate referrals to a variety of providers, agencies and information sources requires further study using mixed methods designs with concurrent control groups. The complementary referral measures we used are promising. BPGs should include specific recommendations on referrals and this information should be tailored to the community setting where implementation is taking place. Nurses can play a vital role in initiating and supporting appropriate patient referrals to a wide spectrum of specialized service providers and to credible information sources such as those available on the Internet. Nurses' familiarity with referral resources does not necessarily change their referral practices. Findings suggest that BPGs should include guidance on effective referral processes. Other patient discharge strategies such as care mapping, the development of clear referral criteria and explicit policies regarding the nurse's role as an initiator of referrals also need to be put in place to reduce the risk of missed referrals and to promote continuity of care.The author(s) declare that they have no competing interests.NE and BD conceived of the evaluation design for this study and developed the nurses' questionnaires. BD led development of the chart audit and patient interview instruments with input from all team members. NE led the psychometric analysis of the referral measures. TV led the teams who developed the best practice guidelines used in the study, and provided overall coordination for the implementation process. JP led the literature review. NE prepared the initial draft of the manuscript. All authors contributed to the interpretation of findings and to writing the final draft of this manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Topographical disorientation represents one of the main consequences of brain injury. Up to now several methodological approaches have been used in the assessment of the brain injured patient's navigational abilities showing a moderate correlation with the impairments observed in everyday contexts.We propose a combination of standardized neuropsychological tests and a more situated virtual reality-based assessment for the evaluation of spatial orientation in brain injured patients.When tested with this virtual reality integrated procedure patients showed performance and execution times congruent with their neuropsychological evaluation. When compared to a control group, patients revealed significantly slower times and greater errors in solving virtual reality based spatial tasks.The use of virtual reality, when combined with classical neuropsychological tests, can provide an effective tool for the study of topographical disorientation. Topographical disorientation, when associated with a complex cognitive impairment, represents one of the main consequences of extended brain injury and occurs most frequently from damage in the parietal/temporal/occipital regions -5.Patients with topographical disorientation revealed impairment in the capacity to orient oneself in and to cope with everyday environments. Despite this statement, up to now most of the evaluation tools for topographical disorientation introduced laboratory methodologies in order to understand how people explore three-dimensional spaces -12.Laboratory evaluation does not support an immediate and direct interaction generally possible in the daily environment, and constitutes an important bias for the evaluation of spatial impairments in brain damage, often making clinicians desire a more ecological approach. Ecological methods, in fact, might help clinicians to observe the strategy used by a patient to explore a natural environment, and to understand the characteristics of the environment utilized to help in familiarization. On the other hand, the observation of a patient in daily contexts generates many questions about the reliability and interpretation of collected data. In order to avoid biases the design of an effective assessment tool that links a reliable evaluation methodology with a more situated observation of spatial behaviors appears to be still needed.A promising way could be to integrate classical evaluation tools with computer-based interactive ones, such as virtual reality, in order to evaluate the navigational capacity of complex environments by neurological patients by observing the types of spatial representations that a patient is able to produce in order to adaptively interact with space within a given activity.Virtual reality (VR) environments, in fact, constitute an interesting opportunity for the evaluation of topographical disorientation, providing a representation of a dynamic nature and interactive environments ,14. In pThe study of spatial cognition has provided evidence of how it can be represented in a cognitive map which can be of the "route" or "survey" type -18. The According to a particularly theoretical orientation, the capability of learning spatial relationships in a large scale environment, and of organizing them into "route" or "survey" types, is influenced not so much by a major familiarity with the environment, but by a series of characteristics of the specific environment, capable of assuming a functional role with the activities an agent performs or is going to perform inside it -23. We pIn order to evaluate patients' spatial abilities with "paper and pencil" tests a neuropsychological assessment was performed. For general cognitive level identification Progressive Raven's Matrixes (PM47) were employed. Token test, Boston Naming test and phonemic and semantic Fluencies were used for verbal abilities evaluation. Memory ability was assessed through Digit and Corsi's span where attention and executive functions were evaluated through the Trial Making test, Attentive matrixes and the Tower of London test. Finally, spatial ability evaluation required the Rey's complex figure, Poppelreuter's test, Benton's line orientation test, Street's Completion test and the Elithorn's Perceptual Maze test.We extended this evaluation by addition of the VR-Maze test and VR-Road Map. We developed these tools  to suppoThe VR-Maze test, depicted in figure The VR-Road Map test, depicted in figure For both the VR systems the possibility to track user's spatial behaviour is provided. Snapshots of the tracking tool is provided in figure Four male patients with brain damage  were tested using paper and pencil neuropsychological evaluation and with the VR-integrated procedure. Patients' performance on VR-Maze test and VR-Road Map test were compared to a control group .All the patients appeared to have deficiencies in spatial knowledge organization based on their neuropsychological assessment. They were all at the same level of deficits in the organization of spatial knowledge. With regard to the VR Maze test, in the comparison to the control group, patients revealed significantly slower execution times in solving tasks  and were able to solve four out of the eight mazes as depicted in figure Figure Both in the VR-maze and in VR-Road Map tests, patients' execution times were higher than those of the control group. Moreover, patients' performance in the VR-maze and in the VR-Road Map tests were lower when compared to the control group.These results underline how patients' performance and execution times in VR tests are congruent with their neuropsychological evaluation.VR environments provide the possibility of an egocentric interaction that will highlight patient's difficulty in the translation of survey spatial knowledge into a route one. It could be considered the main feature of topographical disorientation disease.The integration of virtual reality with traditional evaluation methods may provide an interesting alternative to paper and pencil-based approaches, thereby contributing to an improvement in the evaluation of topographical disorientation .The observation of patients' performance allows an assessment of their difficulty in the translation of survey knowledge to route knowledge. In accordance with their impairment, they were able to memorize sequences of paths when provided in a top-view perspective (the survey one). This residual ability is usually assessed using classical neuropsychological evaluation since paper and pencil materials provide spatial relations mainly from a top-down view. In contrast, the integrated approach we have proposed allows an analysis of the survey-route translation of knowledge. In conclusion, the use of virtual reality appears to provide an effective and objective tool for the study of topographical disorientation when combined with classical neuropsychological tests.The author(s) declare that they have no competing interests.FM, AG, LS, MLR and GR equally participated to the design and execution of the study. All authors read and approved the final manuscript.


Radiofrequency ablation has an important role in the management of post infarction ventricular tachycardia. The mapping and ablation of ventricular tachycardia (VT) is complex and technically challenging. In the era of implantable cardioverter defibrillators, the role of radiofrequency ablation is most commonly reserved as an adjunctive treatment for patients with frequent, symptomatic episodes of ventricular tachycardia. In this setting the procedure has a success rate of around 70-80% and a low complication rate. With improved ability to predict recurrent VT and improvements in mapping and ablation techniques and technologies, the role of radiofrequency ablation should expand further. Radiofrequency ablation (RFA) is the treatment of choice in the management of symptomatic patients with ventricular tachycardia (VT) in the absence of structural heart disease. The role of RFA in-patients with VT in the setting of chronic ischemic heart disease is less well defined. Ventricular tachycardia (VT) is a common complication of ischemic heart disease, with significant associated morbidity and mortality ,2. TradiThe development of anti-tachycardia pacing algorithms has significantly reduced the need for cardioversion  and resuVT in the setting of ischemic heart disease is predominantly manifest as monomorphic VT, caused by stable reentrant circuits ,11. WhilIn simple terms the mechanism of reentry in ischemic heart disease relates to zones of heterogeneous conduction, typically at the edge of myocardial scars. Residual functioning myocytes at the edge of, or interspersed within, myocardial fibrous scar create zones of slow conduction and conduction block . When apThe re-entrant VT circuit utilizes the slow conduction properties of the critical isthmus.  The elecThe diagrammatic representation of re-entry in Electrophysiological mapping techniques are primarily focused to identify appropriate sites for ablation.  In the mapping of VT in the setting of ischemic heart disease, the fundamental task is to identify and understand the critical VT isthmus. A number of different techniques have been developed to guide mapping.Traditional mapping approaches during VT have focused on identification of earliest systolic activation. The principle is that the electrical activation that precedes the QRS complex represents the breakout point of the VT into relatively normal myocardium. Fast moving discrete activity preceding the surface QRS by at least 30 msec is regarded as early activation. As seen in Slow moving activity during diastole can be identified in the critical isthmus during VT ,15. The Entrainment refers to a specific response of an arrhythmia to a pacing stimulus at rates greater than the tachycardia cycle length . Whilst Pacing that leads to classical entrainment will result in temporary QRS fusion. If pacing is conducted from within the critical isthmus of the arrhythmia, the resultant QRS morphology should match that of the VT being studied; this is known as entrainment with concealed fusion or concealed entrainment. During concealed entrainment, the duration from the pacing stimulus to the surface QRS onset can localize the pacing site within the isthmus. The shortest S-QRS will be recorded at the exit zone and this will progressively lengthen as the site of pacing moves along the isthmus towards the entrance zone.When pacing at a site within the re-entry circuit, the post pacing interval, from the last pacing stimuli to the return electrogram seen at the pacing site should be similar to the cycle length of the VT.  With the complexity of the reentry circuits, neither concealed entrainment nor the post-pacing interval are completely accurate in identifying the isthmus zone . The utiMapping during VT can be limited by haemodynamic instability, difficulties in inducing VT and uncertainties regarding the clinical significance of induced VTs. Mapping during sinus rhythm is designed to delineate the anatomical and electrophysiological substrate, which predispose to reentry and VT. Mapping in the area of previous infarction can identify these potential areas of abnormal conduction.Different groups perform substrate mapping using a combination of different techniques. Analysis of electrograms during sinus rhythm can identify regions of fractionated electrograms and late potentials, which are markers of abnormal, slowed conduction. Voltage mapping identifies scar zones and the scar border zones in which most isthmuses are located. Pacing threshold maps add additional information to the voltage map to identify electrically heterogeneous areas. Pacemapping to produce a QRS morphology that is similar to that during VT can roughly localize the site of the reentry circuit exit. The duration from the pacing stimulus to the onset of QRS (S-QRS duration) can further identify abnormal substrate that predisposes to reentry.None of these above techniques have adequate specificity to be used alone, but in combination can successfully identify regions of abnormal conduction. Substrate mapping does not identify a discrete point for ablation, but rather a zone or region of abnormal myocardium with the potential to facilitate reentry.The newer mapping tools utilized in electrophysiology all have the potential to facilitate the mapping and ablation of VT. By providing reproducible anatomical information the mapping tools each have the ability to simplify mapping approaches and to guide the delivery of optimal radiofrequency ablation lesions.CARTO  is the most studied mapping tool to aid ablation of ventricular tachycardia. CARTO is most useful in providing accurate substrate maps. The EnSite 3000 multielectrode array  uses non-contact virtual electrograms which can not only provide myocardial substrate information, but can map ventricular activation with a little as one recorded cardiac cycle.As technology improves, the mapping systems will become an integral part of the study of ventricular tachycardia. In the foreseeable future, however, the mapping tools will provide guidance and accuracy, but will not replace the need for an operator with a full grasp of electrophysiology and anatomy.The ablation of VT in the setting of ischemic heart disease has been performed according to two basic strategies. The first strategy involves induction of ventricular tachycardia, mapping and targeted ablation -27. The Targeted ablation of a single morphology of haemodynamically stable VT can be successful in over 80% of cases -27. UnfoThe linear approach pioneered by Marchlinski  was acutIn the larger reported series, significant complications  occurred in 5 - 10% of patients and minor complications  in a further 5 - 10% of patients -29.Previous series have reported the recurrence of VT following a successful procedure to vary from15 - 40% -25, depeBecause of the difficulties with recognizing and defining clinical VT, we prefer to define success based on the level of stimulation required to induce VT rather than the particular morphology of VT induced . Prior tAcute success - No monomorphic VT induced at refractoriness of 5 extra stimuli.Modified Result - Monomorphic VT only inducible by 2 extra stimuli more aggressive than at baseline.Failed Procedure - Monomorphic VT inducible at similar levels to baseline.Using this protocol we were able to accurately predict the patients who will remain free of further VT following radiofrequency ablation. In patients with a minimum follow up of 12 months the rate of recurrent VT with either a complete success or a modified result was 4%, compared with 66% amongst patients with a failed procedure .At one end of the spectrum, the patient with incessant or intractable ventricular tachycardia, resistant to pharmacotherapy and overdrive pacing and requiring frequent cardioversion is an obvious candidate for ablation of ventricular tachycardia. At the other end of the spectrum there is presently no role for ablation in the sense of primary prevention.Patients with frequent episodes of VT should be considered for ablation. The threshold for deciding to undergo ablation should consider the local expertise, the frequency of episodes, patient and economic factors. Comprehensive data has shown a substantial mortality benefit supporting the use of ICDs in-patients with post infarction VT. At present ablation should ideally be considered to have a role as an adjunct to an ICD in-patients with highly symptomatic VT.As mapping and ablation techniques develop and the accuracy of predicting the long-term outcome improves, the role of RFA may expand, making it the therapy of first choice in a growing proportion of patients. Perhaps with time ICDs may be reserved as the treatment for failed ablation procedures or for prophylactic indications, particularly in parts of the world where widespread implantation of ICDs is financially impractical. Even if ICDs remain justified on the basis of residual uncertainty, the quality of life is likely to be improved by the reduction in discharges resulting from catheter ablation.Radiofrequency catheter ablation of patients with highly symptomatic, sustained, monomorphic post infarction VT can be performed with high success rate and acceptable procedural complication rate. The procedure can be successfully applied to a wide spectrum of patients including those with multiple morphologies of VT and hemodynamically unstable VT. The procedure at present requires extensive understanding of anatomical and electrophysiological principles and is prolonged and technically demanding. Its application beyond a few expert centers is dependent upon electrophysiological and technological advances.