A Simple Geometric Validation Approach to Assess the Basic Behaviour of Space‐ and Time‐ Distributed Models of Epidemic Spread – An Example Using the Ontario Rabies Model

Dynamic mathematical modelling and stochastic simulation of disease–host systems for the purpose of epidemiological analysis offer great opportunities for testing hypotheses, especially when field experiments are impractical or when there is a need to evaluate multiple experimental scenarios. This, combined with the ever increasing computer power available to researchers, has contributed to the development of many mathematical models for epidemic simulations, such as the individual‐based model (IBM). Nevertheless, few of these models undergo extensive validation and proper assessment of intrinsic variability. The Ontario rabies model (ORM) will be used here to exemplify some advantages of appropriate model behaviour validation and to illustrate the use of a simple geometric procedure for testing directional bias in distributed stochastic dynamic model of spread of diseases. Results were obtained through the comparison of 10 000 epizootics resulting from 100 epidemic simulations started using 100 distinct base populations. The analysis results demonstrated a significant directional bias in epidemic dispersion, which prompted further verification of the model code and the identification of a coding error, which was then corrected. Subsequent testing of the corrected code showed that the directional bias could no longer be detected. These results illustrate the importance of proper validation and the importance of sufficient knowledge of the model behaviour to ensure the results will not confound the objectives of the end‐users.     

Carrier Status of Leptospirosis Among Cattle in Sri Lanka: A Zoonotic Threat to Public Health

Leptospirosis is a zoonotic disease of global importance and one of the notifiable diseases in Sri Lanka. Recent studies on human leptospirosis have suggested that the cattle could be one of the important reservoirs for human infection in the country. However, there is a dearth of local information on bovine leptospirosis, including its implications for human transmission. Thus, this study attempted to determine the carrier status of pathogenic Leptospira spp in cattle in Sri Lanka. A total of 164 cattle kidney samples were collected from the meat inspection hall in Colombo city during routine inspection procedures conducted by the municipal veterinary surgeons. The DNA was extracted and subjected to nested PCR for the detection of leptospiral flaB gene. Amplicons were sequenced, and phylogenic distances were calculated. Of 164 samples, 20 (12.2%) were positive for flaB‐PCR. Sequenced amplicons revealed that Leptospira species were deduced to L. borgpetersenii (10/20, 50%), L. kirschneri (7/20, 35%) and L. interrogans (3/20, 15%). The results indicate that a high proportion of the sampled cattle harbour a variety of pathogenic Leptospira spp, which can serve as important reservoirs for human disease.     

A serological Survey of Brucella spp., Salmonella spp., Toxoplasma gondii and Trichinella spp. in Iberian Fattening Pigs Reared in Free‐Range Systems

Zoonotic agents such as Brucella spp., Salmonella spp., Toxoplasma gondii and Trichinella spp., all considered high‐risk zoonotic pathogens by the European Food Safety Agency (EFSA), may cause no symptoms of infection in free‐range pigs yet still have a significant public health impact. A serological survey was therefore performed to determine the history of occurrence of these pathogens in such pigs in southern Spain. A total of 709 serum samples were collected at abattoir from pigs from 79 farms and analysed for specific antibodies against the above pathogens using commercially available ELISA kits. Encysted Trichinella spp. larvae were also sought following the artificial digestion method of diaphragm pillar muscle. The results showed Salmonella spp. to be widely distributed among the sampled herds [73.42%, 95% confidence interval (CI₉₅) 65.6–81.78] and Toxoplasma gondii to be present in over half (58.23%, CI₉₅ 47.33–69.07). The seroprevalence of Brucella spp. was very low (3.8%, CI₉₅ 0.18–7.42), and antibodies against Trichinella spp. were not detected. No encysted Trichinella spp. larvae were microscopically detected.     

High‐Density Dependence But Low Impact on Selected Reproduction Parameters of Brucella suis Biovar 2 in Wild Boar Hunting Estates from South‐Western Spain

Porcine brucellosis is a disease caused by Brucella suis, which is characterized by reproductive disorders in pigs. The number of cases of swine brucellosis has risen in many European countries, likely because of the presence of a wild reservoir of B. suis in wild boar. This study aimed at evaluating factors that may influence the probability of infection with Brucella spp. in wild boar and at assessing the impact of a previous contact with Brucella spp. on reproductive parameters of wild boar. Two hundred and four wild boar living in Extremadura (south‐western Spain) were studied. The presence of anti‐Brucella antibodies was determined using an indirect ELISA, while the presence of living bacteria in genital organs was evaluated through microbiological cultures. Sex, age, density of wild boar in summer and presence of outdoor pigs were selected as possible risk factors for being seropositive for Brucella spp. in wild boar. In addition, reproductive parameters such as breeding status or potential fertility in females and testis weight in males were estimated and related to the presence of anti‐Brucella antibodies. A total of 121 animals were seropositive, resulting in a prevalence of 59.3% (95% CI). In addition, seven isolates of B. suis biovar 2 were obtained. Wild boar density in summer, as well as age and sex, was proposed as factors to explain the probability of Brucella seroconversion, although wild boar density in summer was the key factor. Current measures of reproductive parameters were not influenced by a previous contact with Brucella spp. Isolation of B. suis confirms that wild boar could represent a risk to domestic pig health in the study area. Wild boar density seems to have a great influence in the probability of infections with B. suis and suggests that density management could be useful to control Brucella infection in wild boar.     

Development and Testing of a Field Diagnostic Assay for Peste des Petits Ruminants Virus

We have developed an immunochromatographic test for the diagnosis of peste des petits ruminants (PPR) under field conditions. The diagnostic assay has been tested in the laboratory and also under field conditions in Ivory Coast, Pakistan, Ethiopia and Uganda. The test is carried out on a superficial swab sample (ocular or nasal) and showed a sensitivity of 84% relative to PCR. The specificity was 95% over all nasal and ocular samples. The test detected as little as 10³ TCID₅₀ (50% tissue culture infectious doses) of cell culture‐grown virus, and detected virus isolates representing all four known genetic lineages of peste des petits ruminants virus. Virus could be detected in swabs from animals as early as 4 days post‐infection, at a time when clinical signs were minimal. Feedback from field trials was uniformly positive, suggesting that this diagnostic tool may be useful for current efforts to control the spread of PPR.     

Buscando o motivo da instabilidade hemodinâmica: relato de caso sobre o papel do ultrassom intraoperatório

Background and objectives

A prompt and effective management of trauma patient is necessary. The aim of this case report is to highlight the importance of intraoperative echocardiography as a useful tool in patients suffering from refractory hemodynamic instability no otherwise explained.

Post-fracture Risk Assessment: Target the Centrally Sited Fractures First! A Substudy of NoFRACT

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1–SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm²), total hip (800 versus 876 mg/cm²), and lumbar spine (1024 versus 1062 mg/cm²); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2–SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1–SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Outcomes of metastatic breast cancer patients in relationship to disease‐free interval following primary treatment of localized disease; a pooled analysis of two clinical trials

The aim of the current study is to assess the impact of disease‐free interval (DFI) following treatment of primary localized breast cancer on the outcomes of patients with subsequent metastatic breast cancer treated with first‐line docetaxel chemotherapy. This study is a combined analysis of patient‐level raw data of 604 metastatic breast cancer patients referred for docetaxel first‐line chemotherapy in two clinical trials. Overall survival and time to progression were evaluated according to DFI through Kaplan‐Meier analysis. Multivariate analysis of factors affecting overall survival and time to progression was then conducted through Cox regression analysis. For the overall cohort, shorter DFI is associated with worse overall survival (P < 0.0001). When classified by the hormone receptor status, the shorter interval was associated with worse overall survival in both hormone receptor positive and negative patients (P = 0.009; P = 0.018; respectively). Likewise, shorter DFI is associated with shorter time to progression (P < 0.0001) in the overall cohort. When classified by the hormone receptor status, the shorter interval was associated with shorter time to progression for hormone receptor negative but not positive patients (P = 0.001; P = 0.070; respectively). In multivariate Cox regression analysis, the following factors were associated with worse overall survival: shorter DFI (P < 0.0001), poorer ECOG performance score (P = 0.008) and lower body mass index (P = 0.018). Likewise, in multivariate Cox regression analysis, the following factors were associated with shorter time to progression: shorter DFI (P < 0.0001) and hormone receptor negative status (P = 0.025). Shorter DFI was associated with worse overall survival and shorter time to progression among patients receiving first‐line docetaxel chemotherapy.     

Contemporary management of breast cancer during pregnancy and subsequent lactation in a multicenter cohort of young women with breast cancer

The incidence of breast cancer diagnosed during pregnancy is increasing. We sought to characterize patient, treatment, pregnancy and lactation factors among young women with newly diagnosed breast cancer during pregnancy in a prospective cohort study. We identified all women who were pregnant when diagnosed with invasive breast cancer among those enrolled in the Young Women's Breast Cancer Study (NCT01468246), and collected details on pregnancy, birth and lactation from surveys, and treatment information medical record review. Of 1302 enrolled participants, 976 women with invasive breast cancer completed full baseline surveys, among whom 39 (4.0%) patients reported being pregnant at diagnosis. Median age at diagnosis was 34 years (range: 25‐40), with stage distribution: I, 28%; II, 44%; III, 23%; and IV, 5%. 74% of patients (29/39) had grade 3 tumors, 59% (23/39) ER‐positive, and 31% (12/39) HER2‐positive disease. 23 (59%) had surgery during pregnancy, 4 (17%) during the first trimester. Among the women who had surgery during pregnancy, 61% (14/23) underwent lumpectomy, 35% (8/23) unilateral, and 4% (1/23) bilateral mastectomy. All patients who had chemotherapy (51%, 20/39) received it in second and third trimesters, and had ACx4. There were 31 live births, 2 spontaneous, and 5 therapeutic abortions. Among live births, 16 (41%) were before 37 weeks of gestation. Three women reported breastfeeding. Within 6 months after delivery, comprehensive staging in 13 patients showed upstaging in four patients. In a contemporary cohort of young women with breast cancer, pregnancy at diagnosis is relatively uncommon. Treatment during pregnancy can generally be consistent with standard surgical and chemotherapy approaches, with attention to timing of therapies. Longer‐term outcomes including effects of some timing issues including delayed use of anti‐HER2 therapy on patient outcomes warrant further research.