Characterization of workers or population percentage affected by low-back pain (LPB), sciatica and herniated disc due to whole-body vibrations (WBV).

Whole-body vibrations have several harmful effects on the population's health. The most suitable way to characterize the vibrations is to use the daily vibration exposure A (8) and Vibration Dose Value as specified in Directive 2002/44/EC. Therefore, based on the existing literature, we propose Probit equations that allow us to relate the population percentage affected by the vibration effects (low-back pain, sciatica, and herniated disc) with the A (8) and the Vibration Dose Value. It is worth noting that there is a good correlation between the experimental data and the expressions obtained, especially for low-back pain and herniated discs. Once the expressions have been validated, we analyze the limit values given in the aforementioned legislation, showing that the percentage of the affected population is significant for them. Therefore, this study also proposes new limits based on their own definitions, which are more in line with the results shown in the bibliography.

Nanoplastics are bioaccumulated in fish liver and muscle and cause DNA damage after a chronic exposure.

The extent of the widespread, planetary contamination by plastic waste is difficult to fully capture. Nanoplastics (NPs) are currently in the center of research concerning plastic litter, both for the analytical challenges they pose and for their potential to provoke hazardous effects in organisms. However, there are still many unanswered questions in this multidisciplinary field, with a crucial missing piece being the quantification of NPs in fish tissues after in vivo exposures. Another relevant question that is still greatly unexplored is how a chronic exposure to NPs will affect fish health. This study aims to provide answers to both of these relevant knowledge gaps. To this end, goldfish (Carassius auratus) were exposed to 44 nm polystyrene (PS)-NPs via water for 30 days. Following the exposure, gastrointestinal tract, liver and muscle were sampled for PS-NPs analysis by means of size exclusion chromatography coupled to high resolution mass spectrometry. PS-NPs were detected in all liver and muscle samples of exposed fish, with higher concentrations in liver than in muscle, whereas no PS-NPs were detected in the gastrointestinal tract. Nevertheless, exposure to PS-NPs did not induce changes in hematology parameters nor in cortisol and glucose levels in plasma. On the other hand, even a relatively low concentration of PS-NPs was able to cause DNA damage, measured by an increase in erythrocyte nuclear abnormalities, suggesting that PS-NPs can reach the cell nucleus and cause genotoxicity. These results show for the first time that PS-NPs find their way to fish muscle after chronic exposure, where they bioaccumulate, but do not alter fish survival nor hematological or physiological stress indicators. The accumulation of PS-NPs in fish muscle can represent a threat to human health as a possible route of exposure to small-sized plastics. The present results in a model fish species open windows for future studies in edible fish species.

Identifying and preventing burnout in young oncologists, an overwhelming challenge in the COVID-19 era: a study of the Spanish Society of Medical Oncology (SEOM).

BACKGROUND: Young oncologists are at particular risk of professional burnout, and this could have a significant impact on their health and care of their patients. The coronavirus disease 2019 (COVID-19) pandemic has forced rapid changes in professionals' jobs and training, with the consequent physical and psychological effects. We aimed to characterize burnout levels and determinants in young oncologists, and the effects of the pandemic on their training and health. METHODS: Two online surveys were conducted among oncology residents and young oncology specialists in Spain. The first addressed professional burnout and its determinants before the COVID-19 pandemic, while the second analyzed the impact of the pandemic on health care organization, training, and physical and psychological health in the same population. RESULTS: In total, 243 respondents completed the first survey, and 263 the second; 25.1% reported significant levels of professional burnout. Burnout was more common among medical oncology residents (28.2%), mainly in their second year of training. It was significantly associated with a poor work-life balance, inadequate vacation time, and the burnout score. Nearly three-quarters of respondents (72%) were reassigned to COVID-19 care and 84.3% of residents missed part of their training rotations. Overall, 17.2% of this population reported that they had contracted COVID-19, 37.3% had scores indicating anxiety, and 30.4% moderate to severe depression. Almost a quarter of young oncologists (23.3%) had doubts about their medical vocation. CONCLUSIONS: Burnout affects a considerable number of young oncologists. The COVID-19 pandemic has had a profound impact on causes of burnout, making it even more necessary to periodically monitor it to define appropriate detection and prevention strategies.

Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology).

BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.

Optimal duration of first-line chemotherapy for advanced gastric cancer: data from the AGAMENON registry.

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.

Trifluridine/Tipiracil (TAS-102) for refractory metastatic colorectal cancer in clinical practice: a feasible alternative for patients with good performance status.

INTRODUCTION: Our aim was to assess efficacy and safety and prognostic factors associated with TAS-102 in clinical practice. METHOD: Retrospective, multicenter, and observational study including patients with advanced refractory colorectal cancer who started TAS-102 between March 2016 and August 2018. The primary end point was overall survival (OS). Secondary end points included progression-free survival, toxicity and analyze prognostic factors present at the beginning of TAS-102. RESULT: 84 patients were evaluable. The median OS was 8.30 (95% CI 6.23-9.87) months and PFS was 2.62 (95% CI 2.36-3.05) months. In multivariate analysis, ECOG 0 and reduced dose combined with more cycles were associated with better prognosis. Patients with an ECOG > 0 had worse prognosis (HR 3.34, 95% CI 1.09-10.27, p = 0.035). 95.2% experienced some type of adverse effect and 45.2% had grade ≥ 3 toxicities. CONCLUSION: Results suggest reconsidering TAS-102 in patients with ECOG > 0, something that should be investigated in prospective randomized clinical trials.

Relationship between ultraviolet index (UVI) and first-, second- and third-degree sunburn using the Probit methodology.

In this paper, a relation between the ultraviolet index (UVI) as a Sun exposure time and its effects in the form of burns according to the skin type has been elaborated. Moreover, we present a new expression that relates the intensity of solar radiation and the UVI, as well as expressions to obtain the percentage of population affected both by first and second degree lllsunburn for every skin-type. The results have been adjusted and validated through experimental results taken from the bibliography. Finally, this paper presents a table where the population can easily interpret the UVI values and calculate the maximum time one can be exposed to solar radiation without getting sunburn. In addition, this article aims to raise awareness of the potential harm caused by solar radiation by indicating the percentage of population affected by different types of sunburn depending on skin-type. Moreover, ultraviolet exposure to sunlight could not just result in sunburn, but also have long-term effects on eyes, or even cause immune system disorders or melanoma. Therefore, managing risk perception with this useful table could familiarize the population with actual harm prevention.

Modeling and simulation of different and representative engineering problems using Network Simulation Method.

Mathematical models simulating different and representative engineering problem, atomic dry friction, the moving front problems and elastic and solid mechanics are presented in the form of a set of non-linear, coupled or not coupled differential equations. For different parameters values that influence the solution, the problem is numerically solved by the network method, which provides all the variables of the problems. Although the model is extremely sensitive to the above parameters, no assumptions are considered as regards the linearization of the variables. The design of the models, which are run on standard electrical circuit simulation software, is explained in detail. The network model results are compared with common numerical methods or experimental data, published in the scientific literature, to show the reliability of the model.

Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry.

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.

Key points to optimizing management and research on cancer-associated thrombosis.

Despite the fact that thromboembolism is relatively common in oncology patients and that the interrelationship between thrombotic risk and specific mechanisms of tumorigenesis has long been known, many cardinal elements of prevention and treatment remain unresolved. Among the existing knowledge gaps, the need to validate the Ay scale and compare it to the Khorana index, develop, and standardize the use of predictive biomarkers for thrombotic risk, conduct clinical trials in thromboprophylaxis adapted to thrombotic risk, evaluate the efficacy and safety of direct anticoagulants, select patients who can benefit from anticoagulants for antitumor treatment, validate the EPIPHANY study decision tree to choose patients with low-risk pulmonary embolism, and accumulate more practical experience in special situations (rethrombosis, prolonged therapy beyond 6 months, etc.) are especially remarkable. These gray areas surrounding cancer-related thromboembolism explain why it continues to be a relatively common cause of serious events, at times interfering significantly with the development of new tumor-fighting strategies.

Searching fundamental information in ordinary differential equations. Nondimensionalization technique.

Classical dimensional analysis and nondimensionalization are assumed to be two similar approaches in the search for dimensionless groups. Both techniques, simplify the study of many problems. The first approach does not need to know the mathematical model, being sufficient a deep understanding of the physical phenomenon involved, while the second one begins with the governing equations and reduces them to their dimensionless form by simple mathematical manipulations. In this work, a formal protocol is proposed for applying the nondimensionalization process to ordinary differential equations, linear or not, leading to dimensionless normalized equations from which the resulting dimensionless groups have two inherent properties: In one hand, they are physically interpreted as balances between counteracting quantities in the problem, and on the other hand, they are of the order of magnitude unity. The solutions provided by nondimensionalization are more precise in every case than those from dimensional analysis, as it is illustrated by the applications studied in this work.

The time has come for new models in febrile neutropenia: a practical demonstration of the inadequacy of the MASCC score.

Since its publication more than 15 years ago, the MASCC score has been internationally validated any number of times and recommended by most clinical practice guidelines for the management of febrile neutropenia (FN) around the world. We have used an empirical data-supported simulated scenario to demonstrate that, despite everything, the MASCC score is impractical as a basis for decision-making. A detailed analysis of reasons supporting the clinical irrelevance of this model is performed. First, seven of its eight variables are "innocent bystanders" that contribute little to selecting low-risk candidates for ambulatory management. Secondly, the training series was hardly representative of outpatients with solid tumors and low-risk FN. Finally, the simultaneous inclusion of key variables both in the model and in the outcome explains its successful validation in various series of patients. Alternative methods of prognostic classification, such as the Clinical Index of Stable Febrile Neutropenia, have been specifically validated for patients with solid tumors and should replace the MASCC model in situations of clinical uncertainty.

Evaluation of metal mobility from copper mine tailings in northern Chile.

This work shows the results obtained on a copper mine tailing in the Antofagasta Region, Chile. The tailing was classified as saline-sodic with high concentrations of metals, especially Cu and Fe, with pH 8.4. Our objectives were to (1) compare the physicochemical properties of the tailing with surrounding soils of the mine under study, and (2) evaluate the effect of two amendments (CaCO3 and compost) and their mixtures on Cu(2+), Mn, Fe, Zn, Mg(2+), and K(+) and Ca(2+), SO4 (2-), NO3 (-), and PO4 (3-) leaching. The data obtained were submitted to variance and covariance analysis. The results from the comparison between both substrates showed that in general, the tailing presented greater content of metals. Regarding tailing leaching, pH, electrical conductivity (EC), and concentration of the elements of interest were measured. The statistical analysis showed that Cu(2+) leaching and immobilization of Fe occurred to the greatest extent with compost. The EC decreased throughout the experiment with irrigation and increased upon treatment with compost. The major interactions found among the chemical parameters were (1) tailings without treatment, Cu(2+)/Fe and NO3 (-)/SO4 (2-); (2) tailings treated with CaCO3, Cu(2+)/K(+); (3) tailings treated with compost, NO3 (-)/SO4 (-2) and EC/Cu(2+); and (4) tailings treated with both amendments, EC/Fe and Cu(2+)/Fe. The ANOVA showed that the number of irrigations and the amendments statistically significantly affected the copper mobility and the organic amendment significantly influenced the iron mobility.

[Prescription appropriateness: Indication of citicoline in Primary Care]. / Adecuación prescripción-indicación de citicolina en atención primaria.

INTRODUCTION: The economic situation has made it necessary to optimize resources by adjusting the pharmaceutical expenditure. Citicoline was (2011) the 10th drug by rank of billed amount. Its approved indications are stroke (acute and sub-acute) and head injury, but not cognitive decline associated with age, the presumed indication for most of its use. OBJECTIVES: To assess the conditions of use of citicoline in the Health Area of Tenerife, in order to detect deviations from the indications of use as stipulated in the prescribing information sheet and the pattern of prescription, with emphasis on the analysis of its use in dementia where currently it has no indication or evidence to support it. METHOD: Cross-sectional study of prescription-indication. A 680 patient sample, segmented by reference hospital (error±5%; CI: 0.95%; P=0.5) was taken from the 4036 patients with a prescription of citicoline billed during august-october 2011 (obtained from the prescription database program, Farmacanarias). RESULTS: We found that 123 patients (18.1%) had an appropriate indication. By including the prescription regimen, 28 patients (4.1%) had adequate indication and dose levels, and in only 2 patients (0.2%) an appropriate indication, dosage and duration were found. CONCLUSIONS: "The correct prescription-indication" of citicoline is inappropiate in almost all patients studied. Impact actions are needed in order to optimize prescription, improve patient safety by reducing potential interactions, and the occurrence of adverse effects, and improve efficiency by promoting savings.

Bioequivalence studies for 2 different strengths of irbesartan/hydrochlorothiazide combination in healthy volunteers: 300/25 mg and 300/12.5 mg film-coated tablets.

Two bioequivalence studies of irbesartan (CAS 138402-11-6) and hydrochlorothiazide (CAS 58-93-5) combination at 300/12.5 mg and 300/25 mg strengths were carried out in order to assess the bioequivalence of these film-coated tablet formulations in comparison with the marketed reference formulations.Both studies were performed with 30 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. In each study, test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 72 h following drug administration in case of irbesartan and up to 24 h in case of hydrochlorothiazide. Plasma concentrations of both analytes were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference).For both studies, the 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t [(irbesartan: 300/12.5 mgstrength: 95.33-111.74%. 300/25 mg strength: 91.27-103.93%) (hydrochlorothiazide: 300/12.5 mg strength: 99.63-107.50%. 300/25 mg strength: 95.72-102.24%)] and Cmax [(irbesartan: 300/12.5 mg strength: 98.73-115.03%. 300/25 mg strength: 97.27-112.12%) (hydrochlorothiazide: 300/12.5 mg strength: 97.34-112.06%. 300/25 mg strength: 93.29-106.38%)] were within the bio-equivalence acceptance range of 80-125%.According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that both test formulations are bioequivalent to the corresponding reference formulations. Overall, it was judged that both studies were conducted with a good tolerance of the subjects to study drugs.

Bioequivalence study of two oral formulations of irbesartan 300 mg in healthy volunteers.

A bioequivalence study of 2 irbesartan (CAS 138402-11-6) film-coated tablet formulations was carried out in 40 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 96 h following drug administration. Plasma concentrations of irbesartan were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference). tmax was analysed nonparametrically. The 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t (98.06-109.48%, point estimator 103.61%) and Cmax (88.93-100.87%, point estimator 94.72%) were within the bioequivalence acceptance range of 80-125%. According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that test formulation of irbesartan 300 mg film-coated tablet is bioequivalent to the reference formulation. Overall, it was judged that the study was conducted with a good tolerance of the subjects to both study drugs.

Bioequivalence study of 2 orodispersible formulations of zolmitriptan 5 mg in healthy volunteers.

A bioequivalence study of 2 zolmitriptan (CAS 139264-17-8) orodispersible tablet formulations was carried out in 26 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Plasma concentrations of zolmitriptan and its active metabolite (N-desmethyl-zolmitriptan) were obtained by LC/MS/MS method. Log-transformed AUCs and Cmax values were tested for bioequivalence based on the ratios of the geometric means (test/reference). Tmax was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80-125%. According to the European Guideline 1 it may be therefore concluded that test formulation of zolmitriptan 5 mg orodispersible tablet is bioequivalent to the reference formulation.

Bioequivalence study of 2 orodispersible formulations of ondansetron 8 mg in healthy volunteers.

This study was designed to compare the rate and extent of absorption of 2 oral formulations of ondansetron (CAS 99614-02-5) 8 mg orodispersible tablets in healthy volunteers. 22 subjects were administered ondansetron orodispersible tablets of test and reference formulation in a single-dose, 2-period, 2-sequence, fasting, open-label, crossover and randomised study. Plasma concentrations were determined by LC/MS/MS. Log-transformed AUCs and Cmax values were tested for bioequivalence based on the ratios of the geometric means (test/reference). Tmax was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80-125%. According to the European Guideline [1] it may be therefore concluded that test formulation of ondansetron 8 mg orodispersible tablet is bioequivalent to the reference formulation.