An analysis of the accuracy of COVID-19 country transmission classification.

Accurate epidemiological classification guidelines are essential to ensure implementation of adequate public health and social measures. Here, we investigate two frameworks, published in March 2020 and November 2020 by the World Health Organization (WHO) to categorise transmission risks of COVID-19 infection, and assess how well the countries' self-reported classification tracked their underlying epidemiological situation. We used three modelling approaches: an ordinal longitudinal model, a proportional odds model and a machine learning One-Rule classification algorithm. We applied these models to 202 countries' daily transmission classification and epidemiological data, and study classification accuracy over time for the period April 2020 to June 2021, when WHO stopped publishing country classifications. Overall, the first published WHO classification, purely qualitative, lacked accuracy. The incidence rate within the previous 14 days was the best predictor with an average accuracy throughout the period of study of 61.5%. However, when each week was assessed independently, the models returned predictive accuracies above 50% only in the first weeks of April 2020. In contrast, the second classification, quantitative in nature, increased significantly the accuracy of transmission labels, with values as high as 94%.

An approach to evaluating and benchmarking the mechanical behavior of a surgical mesh prototype designed for the repair of abdominal wall defects.

Ventral hernia repair is a common surgical procedure in abdominal surgery in which surgical mesh has become an essential tool to improve outcomes. To avoid recurrences the mesh needs to mimic the mechanical behavior of the abdominal wall. In this scenario the mechanical properties at the interface between the mesh and its surrounding tissue is critical for the performance of the device and, therefore, the success after surgery. We aimed to characterize and compare the mechanical behavior of the patented prototype mesh Spider and four commercial meshes at the mesh-tissue interface. The prototype mesh was designed based on the hypothesis that the best performance for a large-sized defect in a ventral hernia is obtained when the mesh presents an isotropic behavior. In contrast, commercial meshes presented significant anisotropic behavior. Mechanical properties of the meshes were characterized through uniaxial tensile tests. Longitudinal and transverse axes were defined for each mesh, and samples were cut in each axis orientation. Samples underwent uniaxial tensile testing, from which the elastic modulus in each axis was determined. The degree of anisotropy was calculated as the ratio between the elastic modulus in each axis. An in silico model of the ventral hernia defect was designed to simulate the mesh-tissue interface behavior via finite element method. Meshes were modeled by an hyperelastic orthotropic constitutive model, which allowed isotropic symmetry as particular case for the prototype mesh. Abdominal wall was modeled using a Neo-Hookean model. Once the simulations were launched, mesh-tissue interface behavior was evaluated through the difference between Von Mises stress values on either size of the interface, both on the external and the internal face of the mesh and abdominal wall. Mechanical response was anisotropic for all commercial meshes and isotropic for the Spider prototype. Among commercial, Ultrapro® was highly anisotropic. Tests revealed Gore-Tex® to be the stiffest, followed by Repol Angimesh®, Spider and Ultrapro®; Duramesh™  was found to be the most compliant. Concerning mesh-tissue behavior, simulation results revealed the Spider prototype and Duramesh™  to be the best; Spider due to its uniformity and lower stress difference thanks to its nearly isotropic behavior, and Duramesh™  due to its compliant behavior. Our results suggest that the compromise between stiffness and anisotropy must be considered in order to improve the mechanical performance of the meshes, bearing in mind that for large-sized ventral defects, nearly isotropic mesh ensures better performance.

Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations.

Vector control is widely considered an important tool for lymphatic filariasis (LF) elimination but is not usually included in program budgets and has often been secondary to other policy questions in modelling studies. Evidence from the field demonstrates that vector control can have a large impact on program outcomes and even halt transmission entirely, but implementation is expensive. Models of LF have the potential to inform where and when resources should be focused, but often simplify vector dynamics and focus on capturing human prevalence trends, making them comparatively ill-designed for direct analysis of vector control measures. We review the recent modelling literature and present additional results using a well-established model, highlighting areas of agreement between model predictions and field evidence, and discussing the possible determinants of existing disagreements. We conclude that there are likely to be long-term benefits of vector control, both on accelerating programs and preventing resurgence.

[Diagnostic validity of the isolated measurement of blood pressure in the community pharmacy. Optimum cut-off points]. / Validez de la medida aislada de la presión arterial en farmacia comunitaria. Puntos de corte óptimos.

INTRODUCTION AND OBJECTIVES: The aim of this study is to determine the diagnostic validity of blood pressure measurement in the community pharmacy (CPBP), and to set the cut-off points in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in order to maximise the aforementioned validity, using 24 hour ambulatory blood pressure monitoring (ABPM) as the reference method. MATERIAL AND METHODS: A cross-sectional study with consecutive selection of patient users of the community pharmacy in Andalusia. The CPBP was measured, followed by 24-hour ABPM, which assessed the diagnostic validity of the CPBP. The AUC of the ROC curve was also calculated for SBP and DBP, along with the positive and negative predictive values, for different prevalences and the variation of sensitivity and specificity for the different cut-off points for SBP/DBP. RESULTS: A total of 167 community pharmacy participated with 1,170 patients, of which 1,110 were valid. The CPBP showed a sensitivity of 60.41% (95% CI: 56.40-64.29), and a specificity of the 79.77% (95% CI: 76.12-82.99), a positive predictive values of 76.96% (95% CI: 72.89-80.57), and a negative predictive values of 64.31% (95% CI: 60.55%-67.90%). By using the ROC curve method, the optimal cut-off points are 134/81mm Hg, the point where the sensitivity and specificity and are balanced and the Youden index is maximised. CONCLUSIONS: The sensitivity is relatively low. To improve it tends to lower the cut-off points of SBP and DBP. The calculated optimum is 134/81mm Hg. This provides data on the desirability to review the current cut-off points (140/90), as proposed by the ACC/AHA 2017.

High COX-2 expression in canine mast cell tumours is associated with proliferation, angiogenesis and decreased overall survival.

COX-2 overexpression is associated with several hallmarks of carcinogenesis such as proliferation, angiogenesis, invasion and metastasis. Fifty cases of canine mast cell tumours (MCT) were retrospectively evaluated and submitted to immunohistochemistry for COX-2, CD31, Ki-67, MAC-387 and CD3. Furthermore its relationship with clinicopathological variables and overall survival (OS) was analysed. COX-2 intensity (P = 0.016), but not COX-2 extension nor score was associated with decreased OS and higher grades of malignancy according to Patnaik (P = 0.002) and Kiupel (P < 0.001) grading systems. Cox-2 intensity was also associated with higher Ki-67 scores (P = 0.009), higher mitotic index (P = 0.022) and higher microvascularization density (P = 0.045). No association was observed for COX-2 intensity and CD3-T lymphocyte (P = 0.377) and macrophage infiltration (P = 0.261) by MAC-387 immunollabelling, suggesting an active role of COX-2 in MCT oncogenesis mainly through proliferation and angiogenesis stimulation making it a potentially clinical relevant prognosis marker and therapeutic target.

Results of an early intervention programme for patients with bacteraemia: analysis of prognostic factors and mortality.

BACKGROUND: Bacteraemia is a common cause of morbidity and mortality in patients admitted to hospital. The aim of this study is to analyse the results of a two-year programme for the early optimisation of antibiotic treatment in patients admitted to the Costa del Sol Hospital (Marbella. Spain). METHODS: A prospective two-year cohort study was conducted, evaluating all episodes of bacteraemia at the Costa del Sol Hospital. Epidemiological and microbiological characteristics, any modification of the initial antibiotic treatment, prognostic risk stratification, early mortality related to the episode of bacteraemia, and mortality after the seventh day, were included in the analysis. RESULTS: Seven hundred seventy-three episodes of bacteraemia were treated, 61.6% males and 38.4% females. The mean age was 65.2 years. The condition was most commonly acquired in the community (41.4%). The bacteraemia was most frequently urological in nature (30.5%), and E coli was the microorganism most frequently isolated (31.6%). In 51.1% of the episodes, a modification was made to optimise the treatment. In the first week, 8.2% died from bacteraemia, and 4.5% had died when they were located. The highest rates of death were associated with older patients, nosocomial acquisition, no source, McCabe score rapidly fatal, Charlson index ≥3, Pitt index ≥3 and treatment remained unmodified. CONCLUSION: The existence of bacteraemia control programmes and teams composed of clinicians who are experienced in the treatment of infectious diseases, can improve the disease outcome by enabling more severe episodes of bacteraemia to be recognised and their empirical treatment optimised.

Demographics, epidemiology and the impact of vaccination campaigns in a measles-free world - Can elimination be maintained?

INTRODUCTION: All six WHO regions currently have goals for measles elimination by 2020. Measles vaccination is delivered via routine immunization programmes, which in most sub-Saharan African countries reach children around 9months of age, and supplementary immunization activities (SIAs), which target a wider age range at multi-annual intervals. In the absence of endemic measles circulation, the proportion of individuals susceptible to measles will gradually increase through accumulation of new unvaccinated individuals in each birth cohort, increasing the risk of an epidemic. The impact of SIAs and the financial investment they require, depend on coverage and target age range. MATERIALS AND METHODS: We evaluated the impact of target population age range for periodic SIAs, evaluating outcomes for two different levels of coverage, using a demographic and epidemiological model adapted to reflect populations in 4 sub-Saharan African countries. RESULTS: We found that a single SIA can maintain elimination over short time-scales, even with low routine coverage. However, maintaining elimination for more than a few years is difficult, even with large (high coverage/wide age range) recurrent SIAs, due to the build-up of susceptible individuals. Across the demographic and vaccination contexts investigated, expanding SIAs to target individuals over 10years did not significantly reduce outbreak risk. CONCLUSIONS: Elimination was not maintained in the contexts we evaluated without a second opportunity for vaccination. In the absence of an expanded routine program, SIAs provide a powerful option for providing this second dose. We show that a single high coverage SIA can deliver most key benefits in terms of maintaining elimination, with follow-up campaigns potentially requiring smaller investments. This makes post-campaign evaluation of coverage increasingly relevant to correctly assess future outbreak risk.

High COX-2 expression is associated with increased angiogenesis, proliferation and tumoural inflammatory infiltrate in canine malignant mammary tumours: a multivariate survival study.

COX-2 expression affects mammary tumourigenesis by promoting angiogenesis and cell proliferation, encouraging metastatic spread and tumour-associated inflammation. Samples of canine mammary tumours (n = 109) were submitted to immunohistochemistry to detect COX-2, CD31, VEGF, Ki-67, CD3 and MAC387 expression. Concurrent high expression of COX-2/CD31, COX-2/VEGF, COX-2/Ki-67, COX-2/CD3 and COX-2/MAC was associated with elevated grade of malignancy, presence of intravascular emboli and presence of lymph node metastasis. Tumours with high COX-2 (P < 0.001) and tumours with concurrent expression of high COX-2 and high CD31 (P = 0.008); high VEGF (P < 0.001); high Ki-67 (P < 0.001); high CD3+ T-lymphocytes (P = 0.002) and elevated MAC387 macrophages (P = 0.024) were associated with shorter overall survival (OS) time. Interestingly the groups with high COX-2/CD31 and high COX-2/VEGF retained their significance after multivariate analysis arising as independent predictors of OS. Present data highlight the importance of COX-2 in canine mammary tumourigenesis.

Exploring new biomarkers in the tumour microenvironment of canine inflammatory mammary tumours.

Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (CIMC) are the most aggressive forms of mammary cancer. Current research aims to identify new therapeutic targets. Here, we investigated gene expression levels of biomarkers associated with the inflammatory microenvironment. A total of 32 formalin-fixed paraffin-embedded samples of canine mammary carcinoma (CIMC = 26; non-CIMC = 6) were used and their cDNA subjected to quantitative polymerase chain reaction (qPCR) to establish gene expression levels for mediators commonly implicated in linking carcinogenesis with inflammation. Gene expression differences between CIMC and non-CIMC types were obtained for cyclooxygenase 2 (COX-2) (P = 0.004), synuclein gamma (SNCG) (P = 0.006), tribbles 1 (P = 0.025), vascular endothelial growth factor (VEGF) (P = 0.017) and CSF1R (P = 0.045). Among these biomarkers correlations were found, particularly between SNCG and tribbles 1 (r = 0.512, P = 0.001). The efficient metastasis of CIMC is intimately linked to components in the tumour microenvironment. This study suggests that upregulation and correlation of SNCG and tribbles 1 deserves to be further explored.

Aldehyde dehydrogenase isoform 1 (ALDH1) expression as a predictor of radiosensitivity in laryngeal cancer

Background: Aldehyde dehydrogenase isoform 1 (ALDH1) has been shown to be a marker of cancer stem cells (CSCs). These stem cells may be responsible for tumour perpetuation as well as local and distant invasion. Several studies have shown that CSCs are more chemoradiotherapy (CRT)-resistant and may be responsible for tumour recurrence. Other studies, in contrast, have found ALDH1 expression to be indicative of a better prognosis. Methods: We retrospectively evaluated 84 patients diagnosed and treated for laryngeal cancer between 2006 and 2011. All patients underwent curative-intent radiotherapy or CRT at our institution. 57 of the 84 tumour samples contained sufficient material for ALDH1 assessment. Results: ALDH1 expression was detected in 17.5 % (10/ 57) of the tissue samples. None of the tumours from stage I patients tested positive for ALDH1. The relapse rate in ALDH1 + patients was 10 versus 51.2 % for ALDH1-. No differences in overall survival were observed between the groups; however, disease-free survival was 90 % for the ALDH1 ? group versus 48.9 % for ALDH1- patients (p = 0.034). Conclusion: The patients in this study with ALDH1 ? tumours had better outcomes than their counterparts with ALDH1- tumours. This finding suggests that not all CSCs are resistant to conventional cancer treatments. It may also imply that new methods of correctly identifying these cells are needed (AU)

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Implementation of an extended ZINB model in the study of low levels of natural gastrointestinal nematode infections in adult sheep.

BACKGROUND: In this study, two traits related with resistance to gastrointestinal nematodes (GIN) were measured in 529 adult sheep: faecal egg count (FEC) and activity of immunoglobulin A in plasma (IgA). In dry years, FEC can be very low in semi-extensive systems, such as the one studied here, which makes identifying animals that are resistant or susceptible to infection a difficult task. A zero inflated negative binomial model (ZINB) model was used to calculate the extent of zero inflation for FEC; the model was extended to include information from the IgA responses. RESULTS: In this dataset, 64% of animals had zero FEC while the ZINB model suggested that 38% of sheep had not been recently infected with GIN. Therefore 26% of sheep were predicted to be infected animals with egg counts that were zero or below the detection limit and likely to be relatively resistant to nematode infection. IgA activities of all animals were then used to decide which of the sheep with zero egg counts had been exposed and which sheep had not been recently exposed. Animals with zero FEC and high IgA activity were considered resistant while animals with zero FEC and low IgA activity were considered as not recently infected. For the animals considered as exposed to the infection, the correlations among the studied traits were estimated, and the influence of these traits on the discrimination between unexposed and infected animals was assessed. CONCLUSIONS: The model presented here improved the detection of infected animals with zero FEC. The correlations calculated here will be useful in the development of a reliable index of GIN resistance that could be of assistance for the study of host resistance in studies based on natural infection, especially in adult sheep, and also the design of breeding programs aimed at increasing resistance to parasites.

Ki-67 and PCNA Expression in Canine Mammary Tumors and Adjacent Nonneoplastic Mammary Glands: Prognostic Impact by a Multivariate Survival Analysis.

The assessment of tumor proliferation has been considered a determining prognostic factor in canine mammary tumors (CMTs). However, no studies have assessed the prognostic importance of proliferation in adjacent nonneoplastic mammary glands. We included 64 CMTs (21 benign and 43 malignant) and studied the proliferation index (PI) of Ki-67 and proliferating cell nuclear antigen (PCNA) together with several clinicopathological characteristics. A positive and statistically significant correlation between the PI of Ki-67 and PCNA in tumors and adjacent nonneoplastic mammary glands was observed in benign and malignant tumors. Tumor size, skin ulceration, histological type, mitotic index, nuclear grade, differentiation grade, histological grade of malignancy, lymph node metastasis, Ki-67, and PCNA expression in tumors and adjacent nonneoplastic mammary glands were statistically associated with overall survival by univariate analysis in malignant cases (n = 43). Histological grade of malignancy and high intratumoral PCNA retained their significance by multivariate analysis arising as independent predictors of overall survival. Interestingly, the PI of Ki-67 and PCNA of adjacent nontumoral mammary glands were associated with clinicopathological features of tumor aggressiveness and shorter overall survival, demonstrating the need to better explore this adjacent non-neoplastic tissue.

POSIBLE RESISTENCIA DE Dictyocaulus viviparus AL FENBENDAZOL EN UN BOVINO / POSSIBLE RESISTANCE OF Dictyocaulus viviparus TO FENBENDAZOLE IN A BOVINE

Se describe un caso de posible resistencia al fenbendazol en una ternera Jersey infestada por Dictyocaulus viviparus. En el municipio de Entrerríos (Antioquia, Colombia), una hembra de la raza Jersey de 6 meses de edad, presentó un serio cuadro de bronco-neumonía, el cual no mejoró con la aplicación de fenbendazol y enrofloxacina como terapia de mantenimiento. En la necropsia, se observó un número elevado de parásitos vivos compatibles con Dictyocaulus viviparus, determinando una bronquitis verminosa. Este nematodo, el cual se trata rutinariamente con fenbendazol en las fincas lecheras colombianas, ha demostrado ser resistente frente algunos bencimidazoles; finalmente, se señalan las posibles causas de esta resistencia de Dictyocaulus viviparus en la ternera Jersey.

It describe the clinical case of a possible resistance to fenbendazole in a Jersey calf infested by Dictyocaulus viviparous described. In the municipality of Entrerrios (Antioquia, Colombia) a female Jersey breed of 6 months of age, presented serious sings of bronchopneumonia. which did not improve with the application of fenbendazole and enrofloxacin as maintenance therapy. At the necropsy, a large number of live parasites compatible with Dictyocaulus viviparus were observed, determining a verminous bronchitis. This nematode, which is routinely treated with fenbendazole in Colombian dairy farms, has been proved resistance when is trated with some benzimidazoles. This specific case shows the possible causes of the Dictyocaulus viviparus resistance in Jersey calf.

Aldehyde dehydrogenase isoform 1 (ALDH1) expression as a predictor of radiosensitivity in laryngeal cancer.

BACKGROUND: Aldehyde dehydrogenase isoform 1 (ALDH1) has been shown to be a marker of cancer stem cells (CSCs). These stem cells may be responsible for tumour perpetuation as well as local and distant invasion. Several studies have shown that CSCs are more chemoradiotherapy (CRT)-resistant and may be responsible for tumour recurrence. Other studies, in contrast, have found ALDH1 expression to be indicative of a better prognosis. METHODS: We retrospectively evaluated 84 patients diagnosed and treated for laryngeal cancer between 2006 and 2011. All patients underwent curative-intent radiotherapy or CRT at our institution. 57 of the 84 tumour samples contained sufficient material for ALDH1 assessment. RESULTS: ALDH1 expression was detected in 17.5 % (10/57) of the tissue samples. None of the tumours from stage I patients tested positive for ALDH1. The relapse rate in ALDH1 + patients was 10 versus 51.2 % for ALDH1-. No differences in overall survival were observed between the groups; however, disease-free survival was 90 % for the ALDH1 + group versus 48.9 % for ALDH1- patients (p = 0.034). CONCLUSION: The patients in this study with ALDH1 + tumours had better outcomes than their counterparts with ALDH1- tumours. This finding suggests that not all CSCs are resistant to conventional cancer treatments. It may also imply that new methods of correctly identifying these cells are needed.

Multitrait indices to predict worm length and number in sheep with natural, mixed predominantly Teladorsagia circumcincta infection.

Accurately identifying resistance to gastrointestinal nematode infections requires the ability to identify animals with low and high intensities of infection. The pathogenic effects of nematodes depend upon both the length and number of worms, neither of which can be measured in live animals. Indices that predict these quantities are urgently needed. Monthly fecal egg counts, bodyweights, IgA concentrations and pepsinogen concentrations were measured on Scottish Blackface sheep naturally infected with a mixture of nematodes, predominantly Teladorsagia circumcincta. Worm number and average worm length were available on over 500 necropsied lambs. We derived predictive indices for worm length and number using linear combinations of traits measured in live animals. The correlations between the prediction values and the observed values were 0.55 for worm length and 0.51 for worm number. These indices can be used to identify the most resistance and susceptible lambs.

The impact of an antimicrobial stewardship programme on the use of antimicrobials and the evolution of drug resistance.

Misuse of antibiotics can provoke increased bacterial resistance. There are no immediate prospects of any new broad-spectrum antibiotics, especially any with activity against enterobacteria, coming onto the market. Therefore, programmes should be implemented to optimise antimicrobial therapy. In a quasi-experimental study, the results for the pre-intervention year were compared with those for the 3 years following the application of an antimicrobial stewardship programme. We describe 862 interventions carried out as part of the stewardship programme at the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the empirical antimicrobial treatment with the programme recommendations and the treatment optimisation achieved by reducing the antibiotic spectrum and adjusting the dose, dosing interval and duration of treatment. In addition, we analysed the evolution of the sensitivity profile of the principal microorganisms and the financial savings achieved. 93 % of the treatment recommendations were accepted. The treatment actions taken were to corroborate the empirical treatment (46 % in 2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1 %). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros were obtained. Stewardship programmes are useful tools for optimising antimicrobial therapy. They may contribute to preventing increased bacterial resistance and to reducing the long-term financial cost of antibiotic treatment.

Tumour-associated macrophages are associated with vascular endothelial growth factor expression in canine mammary tumours.

Tumour-associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin-fixed paraffin-embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.

Concurrent expression of cyclo-oxygenase-2 and epidermal growth factor receptor in canine malignant mammary tumours.

Canine mammary tumours (CMTs) are reported to express cyclo-oxygenase (COX)-2 and epidermal growth factor receptor (EGFR); however, no studies have evaluated concurrent expression of these proteins. In this study, 43 malignant CMTs were evaluated immunohistochemically for concurrent expression of COX-2 and EGFR and expression was correlated with malignancy. High COX-2 expression was associated with tumour size (P = 0.033), mitotic index (P = 0.040), nuclear grade (P = 0.021), histological grade of malignancy (P = 0.020) and lymph node metastasis (P = 0.029). High EGFR immunoreactivity was associated with tumour size (P = 0.001), necrosis (P = 0.001), mitotic index (P = 0.022), histological grade of malignancy (P = 0.041) and lymph node metastasis (P = 0.005). Simultaneous high-expression of COX-2 and EGFR was associated with high-nuclear grade (P = 0.049), high-histological grade of malignancy (P = 0.031) and the presence of lymph node metastasis (P = 0.025). A positive correlation between COX-2 and EGFR expression (r = 0.474; P = 0.001) was also observed. These results suggest that combined use of selective inhibitors of COX-2 and EGFR may be a useful approach to the treatment of malignant CMTs.