Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England.

The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 (n = 258,875) compared to BA.1 (n = 984,337) in a large cohort study in England. We estimated the risk of hospital attendance, hospital admission or death using multivariable stratified proportional hazards regression models. After adjustment for confounders, BA.2 cases had lower or similar risks of death (HR = 0.80, 95% CI 0.71-0.90), hospital admission (HR = 0.88, 95% CI 0.83-0.94) and any hospital attendance (HR = 0.98, 95% CI 0.95-1.01). These findings that the risk of severe outcomes following infection with BA.2 SARS-CoV-2 was slightly lower or equivalent to the BA.1 sub-lineage can inform public health strategies in countries where BA.2 is spreading.

Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry.

Comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) are important biomarker tools used for patients with non-small cell lung cancer (NSCLC) given the expanding number of standard-of-care therapies that require companion diagnostic testing. We examined 9450 NSCLC real-world patient samples that underwent both CGP and programmed death-ligand 1 (PD-L1) IHC to understand the biomarker landscape in this patient cohort. By assessing National Comprehensive Cancer Network (NCCN)-recommended biomarkers including genomic alterations, tumor mutational burden (≥10 mutations/Mb cut-off), and PD-L1 expression (Tumor Proportion Score (TPS) ≥ 50% cut-off), we show that CGP + PD-L1 IHC yielded potentially actionable results for 70.5% of the 9,450 patients with NSCLC. Among the remaining 29.5% (2,789/9,450) of patients, 86.7% (2,419/2,789) were potentially eligible for another biomarker-associated therapy and/or clinical trial based on their genomic profile. In addition, in the PD-L1TPS≥50% disease subset, BRAF mutations, MET mutations, MET amplifications, and KRAS mutations were significantly enriched; and in the PD-L1TPS<50%, EGFR mutations, ERBB2 mutations, STK11 mutations, and KEAP1 mutations were enriched. These findings highlight the improved clinical utility of combining CGP with IHC to expand the biomarker-guided therapeutic options available for patients with NSCLC, relative to single biomarker testing alone.

Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas.

INTRODUCTION: Pembrolizumab was approved with an accompanying companion diagnostic (CDx) assay (PD-L1 DAKO 22C3) for urothelial carcinoma (UC). In this study, we further characterize the clinicopathologic and genomic features of UC that are programmed death-ligand 1 (PD-L1) positive. MATERIALS AND METHODS: The cohort of this study consisted of a total of 528 consecutive UC patients with PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP). All PD-L1 IHC testing was performed using the DAKO 22C3 CDx assay for UC. PD-L1 positivity was determined at a combined positive score ≥ 10. RESULTS: A total of 44.5% (235/528) patients with UC were PD-L1positive . A lower PD-L1 positivity rate was detected in primary (42.3%, 148/350) versus metastatic sites (48.9%, 87/178). PD-L1 positivity was dependent on the location of the metastatic sites. CGP revealed PD-L1positive patients had more frequent genomic alterations (GAs) in TP53 (p = .006) and RB1 (p = .003) and less frequent GAs in FGFR3 (p = .001) and MTAP (p = .028). The APOBEC mutational signature and tumor mutational burden (TMB)-high were more common in PD-L1positive patients. By testing patients with UC with CGP, in addition to PD-L1 IHC, an additional 97 patients (18.4%) in the total cohort were eligible for immunotherapy based on TMB status. CONCLUSION: PD-L1positive and PD-L1negative urothelial carcinomas are genomically different. Also, our study provides the framework for future clinical investigation with regard to specimen site selection for PD-L1 testing as well as candidate biomarker genomic alterations that may predict for better response or lack of response to immune checkpoint inhibitors. IMPLICATIONS FOR PRACTICE: In this study, a higher prevalence of TP53 and RB1 alterations and APOBEC mutational signatures in the PD-L1positive urothelial carcinoma disease subset and enrichment of FGFR3 alterations in the PD-L1negative disease subset were found. These data provide the basis for future investigation into the role of these genomic changes as positive and negative predictors of immunotherapy response. Also, differences wer seen in PD-L1 positivity based on the collection site of the sample, which can provide a framework for future clinical trial design and could influence sample selection for PD-L1 testing in patients with urothelial carcinoma when multiple samples are available.

Reduced MFAP5 expression in stroma of gallbladder adenocarcinoma and its potential diagnostic utility.

The diagnosis of invasive adenocarcinoma of the gallbladder can sometimes be challenging. The presence of true desmoplastic reaction facilitates the diagnosis of invasion. However, desmoplasia-like changes can be observed in benign gallbladder conditions, and recognition of desmoplasia may be challenging based on morphology. In this study, we tested the expression pattern of microfibril-associated protein 5 (MFAP5), a promising immunohistochemical marker for desmoplasia, in benign gallbladders with desmoplasia-like reaction and gallbladders with invasive adenocarcinoma. We also evaluated the diagnostic utility of MFAP5 in challenging cases with an interobserver agreement study. The results showed that all benign cases retained intact/positive MFAP5 staining pattern in periglandular connective tissue, whereas 79.3% (23 out of 29) of cases of adenocarcinomas demonstrated diffuse and complete loss of MFAP5 staining in the tumor stroma. Interobserver agreement was improved by 2.66 times when images of MFAP5 immunohistochemistry were provided. In conclusion, MFAP5 expression is downregulated in the desmoplastic stroma of gallbladder adenocarcinoma and may provide a useful diagnostic marker in difficult cases.

Independent and joint contribution of inappropriate complementary feeding and poor water, sanitation and hygiene (WASH) practices to stunted child growth.

The causes of undernutrition are often linked to inappropriate complementary feeding practices and poor households' access to water, sanitation and hygiene (WASH), but limited evidence exists on the combined effect of poor WASH and inappropriate complementary feeding practices on stunted child growth. We assessed the independent and joint contribution of inappropriate complementary feeding and poor WASH practices to stunted growth among children aged 6-23 months in the Jirapa Municipality of Ghana. A community-based cross-sectional analytical study design was used with a sample of 301 mothers/caregivers having children aged 6-23 months. The results indicate that in a multivariable logistic regression model that adjusted for confounders, children receiving both unimproved water and inappropriate complementary feeding had a higher and significant odd of becoming stunted (adjusted odds ratio = 33. 92; 95 % confidence interval 3⋅04, 37⋅17; P = 0⋅004) compared to households having both improved water sources and appropriate complementary feeding practices. Except for unimproved drinking water sources, poor sanitation and hygiene, which comprised the use of unimproved household toilet facilities, washing hands without soap and improper disposal of child faeces were not associated with the risks of stunting among children aged 6-23 months. The combined effect of unimproved water and inappropriate complementary feeding on stunting was greater than either unimproved water only or inappropriate complementary feeding only.

Review: Synergy between mechanistic modelling and data-driven models for modern animal production systems in the era of big data.

Mechanistic models (MMs) have served as causal pathway analysis and 'decision-support' tools within animal production systems for decades. Such models quantitatively define how a biological system works based on causal relationships and use that cumulative biological knowledge to generate predictions and recommendations (in practice) and generate/evaluate hypotheses (in research). Their limitations revolve around obtaining sufficiently accurate inputs, user training and accuracy/precision of predictions on-farm. The new wave in digitalization technologies may negate some of these challenges. New data-driven (DD) modelling methods such as machine learning (ML) and deep learning (DL) examine patterns in data to produce accurate predictions (forecasting, classification of animals, etc.). The deluge of sensor data and new self-learning modelling techniques may address some of the limitations of traditional MM approaches - access to input data (e.g. sensors) and on-farm calibration. However, most of these new methods lack transparency in the reasoning behind predictions, in contrast to MM that have historically been used to translate knowledge into wisdom. The objective of this paper is to propose means to hybridize these two seemingly divergent methodologies to advance the models we use in animal production systems and support movement towards truly knowledge-based precision agriculture. In order to identify potential niches for models in animal production of the future, a cross-species (dairy, swine and poultry) examination of the current state of the art in MM and new DD methodologies (ML, DL analytics) is undertaken. We hypothesize that there are several ways via which synergy may be achieved to advance both our predictive capabilities and system understanding, being: (1) building and utilizing data streams (e.g. intake, rumination behaviour, rumen sensors, activity sensors, environmental sensors, cameras and near IR) to apply MM in real-time and/or with new resolution and capabilities; (2) hybridization of MM and DD approaches where, for example, a ML framework is augmented by MM-generated parameters or predicted outcomes and (3) hybridization of the MM and DD approaches, where biological bounds are placed on parameters within a MM framework, and the DD system parameterizes the MM for individual animals, farms or other such clusters of data. As animal systems modellers, we should expand our toolbox to explore new DD approaches and big data to find opportunities to increase understanding of biological systems, find new patterns in data and move the field towards intelligent, knowledge-based precision agriculture systems.

Methods of extraction of optical properties from diffuse reflectance measurements of ex-vivo human colon tissue using thin film silicon photodetector arrays.

Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a promising technique for characterization of colon tissue. Herein, two methods for extracting the reduced scattering and absorption coefficients ( µ s ' ( λ ) and µ a ( λ ) ) from SRDRS data using lookup tables of simulated diffuse reflectance are reported. Experimental measurements of liquid tissue phantoms performed with a custom multi-pixel silicon SRDRS sensor spanning the 450 - 750 nm wavelength range were used to evaluate the extraction methods, demonstrating that the combined use of spatial and spectral data reduces extraction error compared to use of spectral data alone. Additionally, SRDRS measurements of normal and tumor ex-vivo human colon tissue are presented along with µ s ' ( λ ) and µ a ( λ ) extracted from these measurements.

Cross-serotype interactions and disease outcome prediction of dengue infections in Vietnam.

Dengue pathogenesis is extremely complex. Dengue infections are thought to induce life-long immunity from homologous challenges as well as a multi-factorial heterologous risk enhancement. Here, we use the data collected from a prospective cohort study of dengue infections in schoolchildren in Vietnam to disentangle how serotype interactions modulate clinical disease risk in the year following serum collection. We use multinomial logistic regression to correlate the yearly neutralizing antibody measurements obtained with each infecting serotype in all dengue clinical cases collected over the course of 6 years (2004-2009). This allowed us to extrapolate a fully discretised matrix of serotype interactions, revealing clear signals of increased risk of clinical illness in individuals primed with a previous dengue infection. The sequences of infections which produced a higher risk of dengue fever upon secondary infection are: DEN1 followed by DEN2; DEN1 followed by DEN4; DEN2 followed by DEN3; and DEN4 followed by DEN3. We also used this longitudinal data to train a machine learning algorithm on antibody titre differences between consecutive years to unveil asymptomatic dengue infections and estimate asymptomatic infection to clinical case ratios over time, allowing for a better characterisation of the population's past exposure to different serotypes.

Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using machine learning.

CYD-TDV is the first licensed dengue vaccine for individuals 9-45 (or 60) years of age. Using 12% of the subjects enroled in phase-2b and phase-3 trials for which baseline serostatus was measured, the vaccine-induced protection against virologically confirmed dengue during active surveillance (0-25 months) was found to vary with prior exposure to dengue. Because age and dengue exposure are highly correlated in endemic settings, refined insight into how efficacy varies by serostatus and age is essential to understand the increased risk of hospitalisation observed among vaccinated individuals during the long-term follow-up and to develop safe and effective vaccination strategies. Here we apply machine learning to impute the baseline serostatus for subjects with post-dose 3 titres but missing baseline serostatus. We find evidence for age dependence in efficacy independent of serostatus and estimate that among 9-16 year olds, CYD-TDV is protective against serotypes 1, 3 and 4 regardless of baseline serostatus.

Spatially resolved diffuse reflectance spectroscopy endoscopic sensing with custom Si photodetectors.

Early detection and surveillance of disease progression in epithelial tissue is key to improving long term patient outcomes for colon and esophageal cancers, which account for nearly a quarter of cancer related mortalities worldwide. Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a non-invasive optical technique to sense biological changes at the cellular and sub-cellular level that occur when normal tissue becomes diseased, and has the potential to significantly improve the current standard of care for endoscopic gastrointestinal (GI) screening. Herein the design, fabrication, and characterization of the first custom SRDRS device to enable endoscopic SRDRS GI tissue characterization using a custom silicon (Si) thin film multi-pixel endoscopic optical sensor (MEOS) is described.

Diabetes insipidus after discontinuation of vasopressin infusion for septic shock.

WHAT IS KNOWN AND OBJECTIVE: Despite widespread use of vasopressin for the treatment of septic shock, few cases of diabetes insipidus (DI) following its discontinuation have been reported. CASE SUMMARY: A 54-year-old man presented with pneumonia progressing to septic shock, requiring norepinephrine and vasopressin for refractory hypotension. After clinical improvement, the patient on 3 separate occasions developed polyuria and severe hypernatremia upon discontinuation of vasopressin, with prompt recovery upon its resumption. WHAT IS NEW AND CONCLUSION: Occurrence of DI upon discontinuation of vasopressin infusion appears to be rare, but incidence may be underestimated due to a paucity of published reports. Actual incidence and underlying mechanism of this phenomenon remain to be elucidated.

Towards a methodology to formulate sustainable diets for livestock: accounting for environmental impact in diet formulation.

The objective of this study was to develop a novel methodology that enables pig diets to be formulated explicitly for environmental impact objectives using a Life Cycle Assessment (LCA) approach. To achieve this, the following methodological issues had to be addressed: (1) account for environmental impacts caused by both ingredient choice and nutrient excretion, (2) formulate diets for multiple environmental impact objectives and (3) allow flexibility to identify the optimal nutritional composition for each environmental impact objective. An LCA model based on Canadian pig farms was integrated into a diet formulation tool to compare the use of different ingredients in Eastern and Western Canada. By allowing the feed energy content to vary, it was possible to identify the optimum energy density for different environmental impact objectives, while accounting for the expected effect of energy density on feed intake. A least-cost diet was compared with diets formulated to minimise the following objectives: non-renewable resource use, acidification potential, eutrophication potential, global warming potential and a combined environmental impact score (using these four categories). The resulting environmental impacts were compared using parallel Monte Carlo simulations to account for shared uncertainty. When optimising diets to minimise a single environmental impact category, reductions in the said category were observed in all cases. However, this was at the expense of increasing the impact in other categories and higher dietary costs. The methodology can identify nutritional strategies to minimise environmental impacts, such as increasing the nutritional density of the diets, compared with the least-cost formulation.

Accounting for uncertainty in the quantification of the environmental impacts of Canadian pig farming systems.

The objective of the study was to develop a life cycle assessment (LCA) for pig farming systems that would account for uncertainty and variability in input data and allow systematic environmental impact comparisons between production systems. The environmental impacts of commercial pig production for 2 regions in Canada (Eastern and Western) were compared using a cradle-to-farm gate LCA. These systems had important contrasting characteristics such as typical feed ingredients used, herd performance, and expected emission factors from manure management. The study used detailed production data supplied by the industry and incorporated uncertainty/variation in all major aspects of the system including life cycle inventory data for feed ingredients, animal performance, energy inputs, and emission factors. The impacts were defined using 5 metrics-global warming potential, acidification potential, eutrophication potential (EP), abiotic resource use, and nonrenewable energy use-and were expressed per kilogram carcass weight at farm gate. Eutrophication potential was further separated into marine EP (MEP) and freshwater EP (FEP). Uncertainties in the model inputs were separated into 2 types: uncertainty in the data used to describe the system (α uncertainties) and uncertainty in impact calculations or background data that affects all systems equally (ß uncertainties). The impacts of pig production in the 2 regions were systematically compared based on the differences in the systems (α uncertainties). The method of ascribing uncertainty influenced the outcomes. In eastern systems, EP, MEP, and FEP were lower (P < 0.05) when assuming that all uncertainty in the emission factors for leaching from manure application was ß. This was mainly due to increased EP resulting from field emissions for typical ingredients in western diets. When uncertainty in these emission factors was assumed to be α, only FEP was lower in eastern systems (P < 0.05). The environmental impacts for the other impact categories were not significantly different between the 2 systems, despite their aforementioned differences. In conclusion, a probabilistic approach was used to develop an LCA that systematically dealt with uncertainty in the data when comparing multiple environmental impacts measures in pig farming systems for the first time. The method was used to identify differences between Canadian pig production systems but can also be applied for comparisons between other agricultural systems that include inherent variation.

Physicians declining patient enrollment in a critical care trial: a case study in thromboprophylaxis.

PURPOSE: To analyze the frequency, rationale and determinants of attending physicians requesting that their eligible patients not be approached for participation in a thromboprophylaxis trial. METHODS: Research personnel in 67 centers prospectively documented eligible non-randomized patients due to physicians declining to allow their patients to be approached. RESULTS: In 67 centers, 3,764 patients were enrolled, but 1,460 eligible patients had no consent encounter. For 218 (14.9 %) of these, attending physicians requested that their patients not be approached. The most common reasons included a high risk of bleeding (31.2 %) related to fear of heparin bioaccumulation in renal failure, the presence of an epidural catheter, peri-operative status or other factors; specific preferences for thromboprophylaxis (12.4 %); morbid obesity (9.6 %); uncertain prognosis (6.4 %); general discomfort with research (3.7 %) and unclear reasons (17.0 %). Physicians were more likely to decline when approached by less experienced research personnel; considering those with[10 years of experience as the reference category, the odds ratios (OR) for physician refusals to personnel without trial experience was 10.47 [95 % confidence interval (CI) 2.19-50.02] and those with less than 10 years experience was 1.72 (95 % CI 0.61-4.84). Physicians in open rather than closed units were more likely to decline (OR 4.26; 95 % CI 1.27-14.34). Refusals decreased each year of enrollment compared to the pilot phase. CONCLUSIONS: Tracking, analyzing, interpreting and reporting the rates and reasons for physicians declining to allow their patients to be approached for enrollment provides insights into clinicians' concerns and attitudes to trials. This information can encourage physician communication and education, and potentially enhance efficient recruitment.

The effect of immunization against GnRF on nutrient requirements of male pigs: a review.

In most countries, male pigs are physically castrated soon after birth to reduce the risk of boar taint and to avoid behaviours such as fighting and mounting. However, entire male pigs are more feed efficient and deposit less fat than barrows. In addition, many animal welfare organizations are lobbying for a cessation of castration, with a likelihood that this could lead to inferior pork unless an alternative method is used to control boar taint. An alternative to physical castration is immunization against gonadotrophin releasing factor (GnRF) which allows producers to capitalize on the superior feed efficiency and carcass characteristics of boars without the risk of boar taint. From a physiological perspective, immunized pigs are entire males until shortly after the second dose, typically given 4 to 6 weeks before slaughter. Following full immunization, there is a temporary suppression of testicular function and a hormonal status that resembles that of a barrow. Nutrient requirements will be different in these two phases, before and after full immunization. Given that there have been few published studies comparing the lysine requirements of entire males and barrows in contemporary genotypes, it is useful to use gilt requirements as a benchmark. A series of meta-analyses comparing anti-GnRF immunized boars and physical castrates and use of nutritional models suggest that the lysine requirement of entire males before the second immunization is 5% higher than for gilts, from 25 to 50 kg BW, and by 8% from 50 to 95 kg. Given that the penalty in growth performance for having inadequate dietary lysine is greater in males than in gilts or barrows, it is important to ensure that lysine requirements are met to obtain the maximum benefits of entire male production during this phase. After the second immunization, the lysine requirement of immunized males decreases and may become more like that of barrows. In addition, a consistent effect of full immunization is a marked increase in voluntary feed intake from about 10 days after the second dose. Putting these together, the estimated lysine requirement, expressed in terms of diet composition, falls to 94% of the gilt level. Although general principles can be described now, further research is needed to fully define the lysine requirements of immunized boars. It is important that the temporal pattern of tissue deposition rates and feed intake be explored to be incorporated into models to predict nutrient requirements over the period of rapidly changing metabolism.

Transmission scenarios for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and how to tell them apart.

Detection of human cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection internationally is a global public health concern. Rigorous risk assessment is particularly challenging in a context where surveillance may be subject to under-ascertainment and a selection bias towards more severe cases. We would like to assess whether the virus is capable of causing widespread human epidemics, and whether self-sustaining transmission is already under way. Here we review possible transmission scenarios for MERS-CoV and their implications for risk assessment and control. We discuss how existing data, future investigations and analyses may help in reducing uncertainty and refining the public health risk assessment and present analytical approaches that allow robust assessment of epidemiological characteristics, even from partial and biased surveillance data. Finally, we urge that adequate data be collected on future cases to permit rigorous assessment of the transmission characteristics and severity of MERS-CoV, and the public health threat it may pose. Going beyond minimal case reporting, open international collaboration, under the guidance of the World Health Organization and the International Health Regulations, will impact on how this potential epidemic unfolds and prospects for control.

Adaptación transcultural al castellano del Nursing Activities Score / Transcultural adaptation into Spanish of the Nursing Activities Score

Introducción La valoración de las cargas de enfermería es práctica habitual en el trabajo diario de los cuidados enfermeros, y normalmente se hace utilizando escalas ajenas al medio hispanoparlante, sin tener en cuenta las características de los distintos entornos que difieren de un país a otro. Entre los instrumentos utilizados para la valoración de las cargas de trabajo en enfermería en unidades de cuidados intensivos, Nursing Activities Score (NAS) ha sido descrito como un instrumento útil para medir dichas cargas en estas unidades. Objetivo Adaptar al castellano el NAS para su uso en unidades de cuidados intensivos. Material y métodos Adaptación por el método de traducción-retraducción del NAS mediante traductores de idioma materno inglés y bilingüe (castellano), y traductores con el castellano como idioma materno y alto nivel de inglés, trabajando los traductores por separado. Se obtuvo una versión única en castellano con la que se realizó una prueba piloto en la Unidad de Cuidados Intensivos y Grandes Quemados del Hospital Universitario de Getafe (Madrid, España) con 30 pacientes y 30 enfermeros durante su turno habitual de trabajo. Se consultó, también, con el autor principal del NAS los ítems que supusieron algún tipo de conflicto. Resultados Entre la escala original y la resultante de las retrotraducciones en inglés se obtuvo una buena correspondencia en el 73% de los ítems y una correspondencia apropiada en el restante 27%; ningún ítem fue considerado con correspondencia mala. Conclusión Se ha obtenido una versión adaptada en castellano del NAS (AU)

Introduction Assessment of nursing workload is a common practice in the daily work of nursing care. This is usually done using scales that were not designed for Spanish-speaking countries, which may not take into account the characteristics of the environments that differ from one country to another. The Nursing Activities Score (NAS) has been described as being a useful tool for measuring nursing workload among the instruments used for this measurement in intensive care units. Objective It was aimed to adapt the NAS into Spanish for its use in Spanish intensive care units. Material and methods The NAS was adapted using translation-back translation method with the participation of both native English speakers who were bilingual in Spanish, and Spanish translators with a high level of English. All of the translators worked individually. A single Spanish version of the scale was obtained, after which a pilot test was made in an Intensive Care Major Burns Unit of the University Hospital of Getafe (Madrid, Spain) with 30 patients and 30 nurses during their regular work shift. We also consulted the primary author of the original description of the NAS regarding items that caused some kind of conflict. Results Between the original scale and the result of the back-translations to English, we obtained agreement ratings of good in 73%, and appropriate in the remaining 27%. No item was considered to have bad correspondence. Conclusion We have developed a Spanish translation of the NAS that appears well matched to the original English version (AU)

[Transcultural adaptation into Spanish of the nursing activities score]. / Adaptación transcultural al castellano del nursing activities score.

INTRODUCTION: Assessment of nursing workload is a common practice in the daily work of nursing care. This is usually done using scales that were not designed for Spanish-speaking countries, which may not take into account the characteristics of the environments that differ from one country to another. The Nursing Activities Score (NAS) has been described as being a useful tool for measuring nursing workload among the instruments used for this measurement in intensive care units. OBJECTIVE: It was aimed to adapt the NAS into Spanish for its use in Spanish intensive care units. MATERIAL AND METHODS: The NAS was adapted using translation-back translation method with the participation of both native English speakers who were bilingual in Spanish, and Spanish translators with a high level of English. All of the translators worked individually. A single Spanish version of the scale was obtained, after which a pilot test was made in an Intensive Care Major Burns Unit of the University Hospital of Getafe (Madrid, Spain) with 30 patients and 30 nurses during their regular work shift. We also consulted the primary author of the original description of the NAS regarding items that caused some kind of conflict. RESULTS: Between the original scale and the result of the back-translations to English, we obtained agreement ratings of good in 73%, and appropriate in the remaining 27%. No item was considered to have bad correspondence. CONCLUSION: We have developed a Spanish translation of the NAS that appears well matched to the original English version.

Prognostic value of breast cancer subtypes, Ki-67 proliferation index, age, and pathologic tumor characteristics on breast cancer survival in Caucasian women.

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well-established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER-/PR-/HER2-) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki-67 proliferation index (Ki-67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000-late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan-Meier curve. ER/PR/HER2 status, grade, tumor-node-metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki-67PI was analyzed between ER/PR/HER2 groups using the Kruskal-Wallis, Mann-Whitney U-tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1-16 times more likely to die than patients with stages IA-B and IIA disease, respectively (95% CI 1.17-3.81 through 9.68-28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki-67PI between ER/PR/HER2 subtypes, p < .001, but Ki-67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki-67 proliferation index are not.