Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Infectious Disease Spreading Fought by Multiple Vaccines Having a Prescribed Time Effect.

We propose a framework for the description of the effects of vaccinations on the spreading of an epidemic disease. Different vaccines can be dosed, each providing different immunization times and immunization levels. Differences due to individuals' ages are accounted for through the introduction of either a continuous age structure or a discrete set of age classes. Extensions to gender differences or to distinguish fragile individuals can also be considered. Within this setting, vaccination strategies can be simulated, tested and compared, as is explicitly described through numerical integrations.

An age and space structured SIR model describing the Covid-19 pandemic.

We present an epidemic model capable of describing key features of the Covid-19 pandemic. While capturing several qualitative properties of the virus spreading, it allows to compute the basic reproduction number, the number of deaths due to the virus and various other statistics. Numerical integrations are used to illustrate the adherence of the evolutions described by the model to specific well known real features of the present pandemic. In particular, this model is consistent with the well known relevance of quarantine, shows the dramatic role of care houses and accounts for the increase in the death toll when spatial movements are not constrained. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13362-020-00090-4) contains supplementary material.

An Age and Space Structured SIR Model Describing the Covid-19 Pandemic

We present an epidemic model capable of describing key features of the present Covid-19 pandemic. While capturing several qualitative properties of the virus spreading, it allows to compute the basic reproduction number, the number of deaths due to the virus and various other statistics. Numerical integrations are used to illustrate the relevance of quarantine and the role of care houses.

Special issue: Mathematical Modeling with Measures.

The special issue is available from: http://www.aimspress.com/newsinfo/1132.html.

Protocol for evaluating a workplace intervention within the framework of consultations for suffering at work in French-speaking Switzerland.

INTRODUCTION: Psychosocial suffering involves diverse human, social and economic costs. Some 34.4% of workers in Switzerland report chronic stress related to their jobs. Medical consultations for suffering at work aim to maintain-or renew-patients' abilities to make decisions and act following a diagnosis of psychological suffering related to their work; they also aim to help workers return to their workstations or remain there. Workplace interventions by consulting occupational physicians can go beyond the subjective issues: they can be offered to employees, in anticipation of a return to work when this appears feasible from the outset. OBJECTIVE: To qualitatively evaluate perceptions of workplace interventions and identify their effects by collecting the verbatim statements of employees and their employers. MATERIALS AND METHODS: Qualitative single-centre study of workplace interventions conducted by the Consultation Service for Suffering at Work's occupational physicians for patients seen between January 2015 to December 2017. Nineteen workplace interventions took place, out of 184 different consultations. The verbatim statements of employees and their employers will be collected over a variable timeframe, using semi-structured face-to-face interviews. These will then be recorded, transcribed and analysed. Fourteen patients refused the workplace intervention. Their professional path will be collected for comparison and exploratory purposes. CONCLUSION: This exploratory research project will provide a better understanding of the issues surrounding work-related psychological suffering and of which strategies support patients most effectively.

Optimizing vaccination strategies in an age structured SIR model.

We present a modeling framework based on a structured SIR model where different vaccination strategies can be tested and compared. Vaccinations can be dosed at prescribed ages or at prescribed times to prescribed portions of the susceptible population. Different choices of these prescriptions lead to entirely different evolutions of the disease. Once suitable "costs" are introduced, it is natural to seek, correspondingly, the "best" vaccination strategies. Rigorous results ensure the Lipschitz continuous dependence of various reasonable costs on the control parameters, thus ensuring the existence of optimal controls and suggesting their search, for instance, by means of the steepest descent method.

A modeling framework for biological pest control.

We present an analytic framework where biological pest control can be simulated. Control is enforced through the choice of a time and space dependent function representing the deployment of a species of predators that feed on pests. A sample of different strategies aimed at reducing the presence of pests is considered, evaluated and compared. The strategies explicitly taken into account range, for instance, from the uniform deployment of predators on all the available area over a short/long time interval, to the alternated insertion of predators in different specific regions, to the release of predators in suitably selected regions. The effect of each strategy is measured through a suitably defined cost, essentially representing the total amount of prey present over a given time interval over all the considered region, but the variation in time of the total amount of pests is also evaluated. The analytic framework is provided by an integro-differential hyperbolic-parabolic system of partial differential equations. While prey diffuse according to the usual Laplace operator, predators hunt for prey, moving at finite speed towards regions of higher prey density.

Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes.

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc.

Body weight and risk of molecular breast cancer subtypes among postmenopausal Mediterranean women.

Breast cancer (BC) is the most common malignant tumor in women, obesity is associated with increased BC incidence and mortality and high levels of circulating insulin may negatively impact on cancer incidence. In the present study, we investigated whether the strength of several anthropometric and metabolic parameters varies between BC molecular subtypes. Eligible cases were 991 non-metastatic BC patients recruited between January 2009 and December 2013. Anthropometric, clinical and immunohistochemical features were measured. Multivariate logistic regression models were built to assess HER2 positive BC risk, comparing (a) triple positive (TP) with luminal A, luminal B and triple negative (TN) and (b) HER2-enriched group with luminal A, luminal B and TN. We stratified patients in pre- and post-menopause: significant differences emerged for luminal A in relation to age: they were more likely to be older compared to other groups. Among postmenopausal patients, the adjusted multivariate analysis showed that high BMI and high waist circumference were inversely correlated to TP subtype when compared to luminal B (OR=0.48 and OR=0.49, respectively). Conversely, HOMA-IR was a risk factor for TP when compared to luminal A and TN (OR=2.47 and OR=3.15, respectively). Our findings suggest a potential role of higher abdominal fat in the development of specific BC molecular subtypes in postmenopausal women. Moreover, they support a potential role of insulin resistance in the development of HER2 positive BC, although this role appears to be stronger when hormone receptors are co-expressed, suggesting a difference in the etiology of these two BC subtypes.

Preface to '' Modeling with measures ''.

Different communities met in the research workshop ``Modeling with Measures" that took place at the Lorentz Center (Leiden, The Netherlands) during 26th--30th of August 2013. They were groups of researchers active in the following fields.

Stability and optimization in structured population models on graphs.

We prove existence and uniqueness of solutions, continuous dependence from the initial datum and stability with respect to the boundary condition in a class of initial--boundary value problems for systems of balance laws. The particular choice of the boundary condition allows to comprehend models with very different structures. In particular, we consider a juvenile-adult model, the problem of the optimal mating ratio and a model for the optimal management of biological resources. The stability result obtained allows to tackle various optimal management/control problems, providing sufficient conditions for the existence of optimal choices/controls.

Intraoperative radiotherapy in early breast cancer.

BACKGROUND: Intraoperative radiotherapy (IORT) constitutes a paradigm shift from the conventional 3-5 weeks of whole-breast external beam radiotherapy (EBRT). IORT enables delivery of radiation at the time of excision of the breast tumour, targeting the area at highest risk of recurrence, while minimizing excessive radiation exposure to healthy breast tissue. The rationale for IORT is based on the observation that over 90 per cent of local recurrences after breast-conserving surgery occur at or near the original operation site. METHODS: This article reviews trials of IORT delivered with different techniques and devices. RESULTS: IORT is a very attractive option for delivering radiotherapy, reducing the traditional fractionated treatment to a single fraction administered at the time of surgery. IORT has been shown to be associated with reduced toxicity and has several potential benefits over EBRT. Only two randomized clinical trials have been published to date. The TARGIT-A and ELIOT trials have demonstrated that IORT is associated with a low rate of local recurrence, although higher than that after EBRT (TARGIT-A: 3·3 versus 1·3 per cent respectively, P = 0·042; ELIOT: 4·4 versus 0·4 per cent, P < 0·001). However, the local recurrence rate for IORT fell within the predefined 2·5 per cent non-inferiority margin in TARGIT-A, and the 7·5 per cent equivalence margin in ELIOT. CONCLUSION: Longer follow-up data from existing trials, optimization of patient criteria and cost-effectiveness analyses are needed. Based on the current evidence, IORT can be offered as an alternative to EBRT to selected patients within agreed protocols, and outcomes should be monitored within national registries.

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.

OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer.

BACKGROUND: Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with triple-negative large operable breast cancer after the administration of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles. The safety and efficacy data of the initial population were updated, with inclusion of additional experience with the same therapy. METHODS: Patients with triple-negative large operable breast cancer (T2-T3 N0-1; T > 3 cm) received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel (Taxol) 120 mg/m2, with granulocyte colony-stimulating factor (5 microg/kg days 3-5) support. RESULTS: Overall 74 consecutive patients (T2/T3 = 35/39; N0/N+ = 26/48) were treated, from May 1999 to May 2008. At pathological assessment, 46 women (62%; 95% confidence interval 50-73) showed pCR in both breast and axilla. At a 41-month median follow-up (range 3-119), 13 events (nine distant metastases) had occurred, 5-year projected disease-free survival (DFS) and distant disease-free survival being 76% and 84%, respectively. Five-year DFS was 90% and 56% in pCRs and non-pCRs, respectively. Severe neutropenia and anemia occurred in 23 (31%) and eight (10.8%) patients, respectively. Severe non-hematological toxicity was recorded in <20% of patients. Peripheral neuropathy was quite frequent but never severe. CONCLUSIONS: Eight weekly PET cycles are a highly effective primary treatment in women with triple-negative large operable breast cancer. This approach results in a very promising long-term DFS in this poor prognosis population. This triplet regimen is worthy of evaluation in phase III trials.

Outcome analysis of breast cancer patients receiving breast-conserving surgery in Southern Italy.

The purpose of the current analysis was to evaluate the outcome of patients enrolled at the National Cancer Institute of Naples between 1997 and 2000, who underwent breast-conserving surgery. Between January 1997 and December 2000, 946 patients had been diagnosed with T1 or T2 (<3 cm) breast carcinoma. At the time of the present analysis (31-12-2005), all patients had been followed for >5 years. A Cox proportional hazards model was performed. Overall, 7-year Locoregional Relapse-free survival (LRFS) and Distant Relapse-free Survival (DRFS) rates were 95.9% and 88.4%, respectively. Seven-year DRFS was 91.2% and 79.3% in T1 and T2 stage, respectively (p<0.0001). Multivariate Cox analysis indicated that number of positive lymph-nodes and hormone receptor status were significantly associated with prognosis. Our findings confirm that early diagnosed breast cancer, treated with breast-conserving surgery, is associated with a very good prognosis in patients referred to an Institution which may be considered as representative of similar Cancer Institutes of Southern Italy. The risk of local relapse was found to be very low (4%), although a longer follow-up is needed to draw definitive conclusions.

Radiofrequency ablation in patients with primary breast carcinoma: a pilot study in 26 patients.

BACKGROUND: The authors performed a pilot trial of ultrasound-guided percutaneous radiofrequency ablation (RFA) in patients with T1 and T2 breast tumors 1) to confirm complete coagulative necrosis of tumor tissue and 2) to determine the safety and complications related to this treatment. METHODS: Twenty-six patients with biopsy-proven, invasive breast carcinoma underwent RFA of their breast tumors followed by immediate resection. Treatment was planned to ablate the tumor and a 5 mm margin of surrounding breast tissue. Tumor viability after RFA was assessed by hematoxylin and eosin and nicotinamide adenine dinucleotide vital staining. RESULTS: Twenty patients (77%) had T1 tumors, and six patients (23%) had T2 tumors. The mean greatest dimension of tumors that were treated with RFA was 1.8 cm (range, 0.7-3.0 cm). The mean treatment time for two-phase RFA treatment was 15 minutes and 23 seconds (range, from 6 minutes and 25 seconds to 24 minutes and 54 seconds). Coagulation necrosis of the tumor was complete in 25 of 26 patients (96%): One patient had a microscopic focus of viable tissue adjacent to the needle shaft site. A single patient (1 of 26 patients; 4%) had a complication related to RFA: a full thickness burn of the skin overlying a tumor that was immediately beneath the skin. CONCLUSIONS: This pilot experience with RFA in the treatment of patients with early-stage, primary breast carcinoma revealed that 1) coagulative necrosis of the entire tumor occurred in 96% of the patients, and 2) the treatment was safe, with only a 4% complication rate. The authors have initiated a trial of RFA alone (no resection) for patients with T1 and T2 breast tumors that will include sentinel lymph node mapping and postablation irradiation.

Long-acting versus short-acting cephalosporins for preoperative prophylaxis in breast surgery: A randomized double-blind trial involving 1,766 patients.

Postoperative infectious complications after breast surgery may result in significant morbidity, psychological trauma, and additional costs. We assessed the efficacy of preoperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1,766 patients undergoing breast surgery. From January 1, 1996 to August 31, 1997, all eligible patients were assigned randomly to receive a single dose of ceftriaxone (2 g) or ceftazidime (2 g) given intravenously at the induction of anesthesia, with no further doses. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. The patients who received ceftriaxone prophylaxis had 54. 4% fewer overall infections than those who received ceftazidime prophylaxis. Wound infection occurred in 0.45% of the ceftriaxone recipients (2 of 883) and 0.91% of the ceftazidime recipients (8 of 883). This prospective randomized double-blind study showed that the long-acting regimen containing ceftriaxone is more cost-effective than the short-acting ceftazidime in preventing postoperative infections in patients subjected to breast surgery.