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.

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.

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.

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.

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.

Comparison of metabolic, hematological, and peripheral blood leukocyte cytokine profiles of dairy cows and heifers during the periparturient period.

The periparturient period presents major physiological challenges for the dairy cow. It is a period that is affected by metabolic stressors, major changes in endocrine status, and altered immune function, which together result in an increased risk of disease. Immunological, hematological, and metabolic profiles from the periparturient period of heifers (primipara) were compared with those of cows (pluripara) to test the hypothesis that at the time of calving they have qualitatively different peripheral blood profiles. Blood samples were collected from 22 Holstein-Friesian animals on 3 occasions: approximately 2 wk before calving, within 24h after calving, and approximately 2 wk after calving. Quantitative PCR was used to measure the expression of a selected set of cytokines and receptors by peripheral blood leukocytes. Additional analyses included hemoglobin concentration, red cell, platelet and white cell counts (total and differentiated), and clinical diagnostic biochemical profiles. Total leukocyte counts, neutrophils, and lymphocytes were higher in heifers than cows before calving and within 24h after calving. Alkaline phosphatase was consistently higher in heifers than cows and several significant differences were observed between the 2 groups with regards to cytokine and cytokine-receptor mRNA expression. The results warrant further investigation from the perspective of identifying risk factors for metabolic and parturient disease in dairy cattle.

Safety and effectiveness of gastric balloons associated with hypocaloric diet for the treatment of obesity.

INTRODUCTION: intragastric balloons provide early satiety and thereby induce short-term weight loss. The aim of this study was to evaluate safety and short and medium-term effectiveness of gastric balloons associated to hypocaloric diet in obesity. MATERIAL AND METHODS: from May 2004 to June 2011 91 obese patients, body mass index (BMI) 45.2 +/- 7.2 kg/m2 were prospectively followed after endoscopic implantation of a gastric balloon associated to restricted diet. Successful therapy was defined as percent loss of total weight (%LTW) > or = 5 % at six months after balloon placement and 6 and 12 months after their withdrawal. All analyses followed intention-to treat principles considering significant p-values < 0.05. RESULTS: we placed 73 fluid-filled balloons (80.2 %) and 18 air-filled ones (19.8 %). Compared to baseline values, at 6-month 73.7 % subjects succeeded, showing significant reductions in weight (13.3 +/- 8.8 kg), BMI (5 +/- 3.4 kg/m2) (p < 0.0001), with % LTW 11 +/- 7 %. Six and twelve months after retrieval 45.1 % and 28.6 % patients reached % LTW > or = 5 %. Short-term and medium-term effectiveness was negatively associated to obesity in first-grade relatives (p = 0.003 and p = 0.04). Higher weight loss 6 months after balloon placement independently predicted medium-term effectiveness (p = 0.0001). Mortality was absent but there were two spontaneous deflations of air-filled balloons and severe withdrawal difficulties in 8 patients, leading to surgery in one case. Retrieval complications associated to air-filled balloons (p = 0.0005). CONCLUSIONS: in obesity, effectiveness of gastric balloons associated to hypocaloric diet decreases over time.Complications occurred mainly in the retrieval endoscopic procedure and related to air-filled balloons.

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.

Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study.

BACKGROUND: The objectives of this epidemiological, prospective study were to describe the characteristics of cytomegalovirus (CMV) infection in heart transplant (HT) recipients and to identify the variables that may influence the development of CMV viremia and CMV disease in these patients. METHODS: HT recipients ≥18 years of age (n=199) were included in the study. Variables studied included CMV serostatus, immunosuppressive treatment, and administration of anti-CMV prophylaxis. RESULTS: The mean age of the population was 52 years, and 84% were males. Immunosuppressive regimens were administered as induction therapy to 92.5% of patients; 88.5% of patients received calcineurin inhibitors as maintenance therapy. Anti-CMV treatment was given to 59% of 199 patients as prophylaxis (70%), preemptive therapy (10%), or to treat CMV infection (20%). Overall, 43% of patients had at least 1 positive viremia test. No patient with a high-risk serostatus (donor+/recipient-) receiving prophylaxis developed CMV syndrome, and only 2.5% of 199 patients developed CMV invasive disease. Multivariate analysis showed that having a positive donor CMV serostatus was associated with an increased risk of developing CMV viremia (P<0.012), while use of mammalian target of rapamycin (mTOR) inhibitors was associated with a decreased risk (P=0.005). CONCLUSIONS: In a population of HT recipients, the CMV infection rate was similar to that seen in previous studies, but the progression to overt CMV disease was very low. Having a CMV-positive donor was identified as an independent risk factor for developing CMV viremia, while the use of mTOR inhibitors was protective against viremia.

Ultrasonography is an accurate technique for the diagnosis of gastrointestinal tumors in patients without localizing symptoms.

INTRODUCTION AND OBJECTIVES: This study compared the accuracy of ultrasonography in the diagnosis of gastrointestinal tumors in patients with several degrees of clinical suspicion. MATERIAL AND METHODS: We recruited patients that were suspect for gastrointestinal neoplasia but with no evidence of localizing symptoms (group A), and patients that were suspect for colon cancer (group B) or for gastric cancer (group C). Accuracy in the diagnosis was compared for: gastric cancer in groups A and C, and for colon cancer in groups A and B. The comparison was made by using the contingency coefficient, which quantifies coincidence of endoscopic and ultrasonographic diagnoses. RESULTS: Seventy-nine patients were included in group A (48 males), wherein 12 colon and 5 gastric neoplasms were detected. Group B was comprised of 153 patients (78 males) and included 66 patients with colorectal cancer (CCR). Group C contained 58 patients (35 males), 31 of whom were diagnosed with gastric cancer. The accuracy of sonography for diagnosing colon cancer was 95.5% for group A and 87.5% for group B. The contingency coefficient for endoscopy vs. ultrasonography was greater for group A: 0.658 than for group B: 0.549. The diagnostic accuracy for gastric cancer was 97.4% for group A and 86.2% for group C. The contingency coefficient between endoscopic and ultrasonographic diagnoses was also greater in group A (0.618) than in group C (0.588). CONCLUSIONS: The accuracy of ultrasonography in diagnosing colon and gastric cancer is not lower in patients without localizing symptoms.

[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.

Malignancy after heart transplantation: incidence, prognosis and risk factors.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

Fibrin deposits and organ failure in newborn foals with severe septicemia.

BACKGROUND: Septicemia in human neonates frequently is complicated by activation of the coagulation system, disseminated intravascular coagulation (DIC) and multiple organ failure syndrome, which may contribute to high mortality. In adult horses with DIC, the lung has been the organ most frequently affected by fibrin deposits. In addition, in vivo studies suggest that hemostatic mechanisms may be immature in foals < 1-day old. HYPOTHESIS: Newborn foals with severe septicemia have fibrin deposits in their tissues independently of their age, and these fibrin deposits are associated with organ failure. ANIMALS: Thirty-two septic and 4 nonseptic newborn foals euthanized for poor prognosis. METHODS: Tissue samples (kidney, lung, and liver) collected on postmortem examination were stained with phosphotungstic acid hematoxylin (PTAH) and immunohistochemistry (IHC) for blind histologic examination. A fibrin score (grades 0-4) was established for each tissue sample and for each foal. Medical records were reviewed for assessing clinical evidence of organ failure during hospitalization. RESULTS: Fibrin deposits were found in most septic foals (28/32 when using IHC and 21/32 when using PTAH), independently of the age of the foal. The lung was the most affected tissue (97% of the septic foals). Additionally, organ failure was diagnosed in 18/32 septic foals (8 with respiratory failure, 14 with renal failure), although a statistical association with severe fibrin deposition was not identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Nonsurviving septic foals have fibrin deposits in their tissues, a finding consistent with capillary microthrombosis and DIC.

The puc1 cyclin regulates the G1 phase of the fission yeast cell cycle in response to cell size.

Eukaryotic cells coordinate cell size with cell division by regulating the length of the G1 and G2 phases of the cell cycle. In fission yeast, the length of the G1 phase depends on a precise balance between levels of positive (cig1, cig2, puc1, and cdc13 cyclins) and negative (rum1 and ste9-APC) regulators of cdc2. Early in G1, cyclin proteolysis and rum1 inhibition keep the cdc2/cyclin complexes inactive. At the end of G1, the balance is reversed and cdc2/cyclin activity down-regulates both rum1 and the cyclin-degrading activity of the APC. Here we present data showing that the puc1 cyclin, a close relative of the Cln cyclins in budding yeast, plays an important role in regulating the length of G1. Fission yeast cells lacking cig1 and cig2 have a cell cycle distribution similar to that of wild-type cells, with a short G1 and a long G2. However, when the puc1(+) gene is deleted in this genetic background, the length of G1 is extended and these cells undergo S phase with a greater cell size than wild-type cells. This G1 delay is completely abolished in cells lacking rum1. Cdc2/puc1 function may be important to down-regulate the rum1 Cdk inhibitor at the end of G1.

[Usefulness of digestive ultrasonography in the assessment of ulcerative colitis extent]. / Utilidad de la ecografía en la valoración de la extensión de la colitis ulcerosa.

INTRODUCTION: A full examination of the colon should be avoided upon finding severe endoscopic lesions in patients with ulcerative colitis. However, knowledge of the precise extent of disease is quite important for disease prognosis and the making of therapeutic decisions. Therefore, any validation of a non-invasive technique to assess the extent of ulcerative colitis gains a lot of interest and importance. MATERIAL AND METHOD: The study included patients that were previously diagnosed of having ulcerative colitis or were beginning to suffer from the disease. A prospective and blind evaluation was carried out to determine the precision of digestive ultrasonography in assessment of ulcerative colitis extent. All ultrasonography was carried out by the same person and was always performed prior to carrying out a full endoscopic study, which is used as the gold standard. The hydrocolonic ultrasonograpy technique was not used in any of the cases. RESULTS: A total of 20 patients -13 males (65%) and 7 females (35%), with an average age of 51.7 years (aged between 24-82 years)- were included in the study. Endoscopic studies revealed severe disease in 5 cases (25%), moderate disease in 12 patients (60%), and mild lesions in the 3 remaining cases (15%). A colonic ultrasonogram was considered satisfactory in 18 cases (90%), and the extent of disease as established by ultrasonography was in all cases consistent with that established through colonoscopy: 3 patients (16.6%) had ulcerative proctitis, 9 patients (50%) had left-sided ulcerative colitis, and 6 (33.3%) had extensive colitis. CONCLUSIONS: Digestive ultrasonography allows to study the colon in most patients, especially when inflammatory activity is present, and provides a greater accuracy in assessing ulcerative colitis extent, which is independent of its activity level.