Ten-year assessment of a cancer fast-track programme to connect primary care with oncology: reducing time from initial symptoms to diagnosis and treatment initiation.

BACKGROUND: Cancer is the second leading cause of mortality worldwide. Integrating different levels of care by implementing screening programmes, extending diagnostic tools and applying therapeutic advances may increase survival. We implemented a cancer fast-track programme (CFP) to shorten the time between suspected cancer symptoms, diagnosis and therapy initiation. PATIENTS AND METHODS: Descriptive data were collected from the 10 years since the CFP was implemented (2009-2019) at the Clinico-Malvarrosa Health Department in Valencia, Spain. General practitioners (GPs), an oncology coordinator and 11 specialists designed guidelines for GP patient referral to the CFP, including criteria for breast, digestive, gynaecological, lung, urological, dermatological, head and neck, and soft tissue cancers. Patients with enlarged lymph nodes and constitutional symptoms were also considered. On identifying patients with suspected cancer, GPs sent a case proposal to the oncology coordinator. If criteria were met, an appointment was quickly made with the patient. We analysed the timeline of each stage of the process. RESULTS: A total of 4493 suspected cancer cases were submitted to the CFP, of whom 4019 were seen by the corresponding specialist. Cancer was confirmed in 1098 (27.3%) patients: breast cancer in 33%, urological cancers in 22%, gastrointestinal cancer in 19% and lung cancer in 15%. The median time from submission to cancer testing was 11 days, and diagnosis was reached in a median of 19 days. Treatment was started at a median of 34 days from diagnosis. CONCLUSIONS: The findings of this study show that the interval from GP patient referral to specialist testing, cancer diagnosis and start of therapy can be reduced. Implementation of the CFP enabled most patients to begin curative intended treatment, and required only minimal resources in our setting.

Impact of the marine litter pollution on the Mediterranean biodiversity: A risk assessment study with focus on the marine protected areas.

In this paper a novel methodology to assess the risk of marine litter (ML) pollution in the Mediterranean Sea is implemented. In this approach, the hazard component is estimated using a state-of-the-art 3D modeling system, which allows the simulation of floating and sinking ML particles; the exposure component is defined from biodiversity estimates; and the vulnerability is related to ML ingestion rates of each species. The results show that the hot-spots for the ML risk concentrate in the coastal regions, and are mainly conditioned by the biodiversity in the region. A dedicated analysis on the marine protected areas shows that the risk therein is controlled by the proximity to ML sources and that their present-day protection levels are not effective in the case of ML pollution. Only a reduction of ML at the sources could reduce the impact of ML pollution in protected areas.

Mobile robotic platforms for the acoustic tracking of deep-sea demersal fishery resources.

Knowing the displacement capacity and mobility patterns of industrially exploited (i.e., fished) marine resources is key to establishing effective conservation management strategies in human-impacted marine ecosystems. Acquiring accurate behavioral information of deep-sea fished ecosystems is necessary to establish the sizes of marine protected areas within the framework of large international societal programs (e.g., European Community H2020, as part of the Blue Growth economic strategy). However, such information is currently scarce, and high-frequency and prolonged data collection is rarely available. Here, we report the implementation of autonomous underwater vehicles and remotely operated vehicles as an aid for acoustic long-baseline localization systems for autonomous tracking of Norway lobster (Nephrops norvegicus), one of the key living resources exploited in European waters. In combination with seafloor moored acoustic receivers, we detected and tracked the movements of 33 tagged lobsters at 400-m depth for more than 3 months. We also identified the best procedures to localize both the acoustic receivers and the tagged lobsters, based on algorithms designed for off-the-shelf acoustic tags identification. Autonomous mobile platforms that deliver data on animal behavior beyond traditional fixed platform capabilities represent an advance for prolonged, in situ monitoring of deep-sea benthic animal behavior at meter spatial scales.

[Factors related to work overload that affect health, financial, occupational, and social activities of the primary caregiver]. / Factores relacionados con la sobrecarga que intervienen sobre la salud, las actividades económicas, laborales y sociales de los cuidadores principales de pacientes crónicos.

OBJECTIVE: To determine the areas of the life of primary caregivers (CP) that may be affected by caring for a patient, as well as the CP variables: health, occupational, economic and social problems, as well as the role that CP overload can play. MATERIAL AND METHODS: A descriptive cross-sectional study was conducted on 167 dependent chronic patients and their CPs. It included and analysis on the impact of caring about health, occupational, and economic problems, as well as maintaining social relationships in CP. A record was made of, demographic variables, age and gender, care, activities, time to care. For the dependent patients, the psychosocial typology of their disease, chronology, dependence, disability, and immobility was studied. The Zarit scale reduced by 8 items has been used for the study of the overload of CPs. RESULTS: More than two-thirds (68.8%) of CPs had health problems, 20.9% economic, 19.6% occupational, and 50.9% for positive family and social relationships. The health impact of CPs is related to psychosocial A typology, an increased level of dependence and immobility, gender, and greater number of care activities. The impact on work activities is related to age (66 years) gender, and home coexistence. The impact on social relationships is only related to kinship. Economic problems have no relationship to patient variables. The overload of CPs is related to health, work, financial, and social problems CONCLUSIONS: The health, financial, occupational, and social impact of CPs relate to variables of the sick person and CP, and especially to the overload perceived by the CPs.

Significant differences in access to tests and treatments for multiple myeloma between public and private systems in Latin America. Results of a Latin American survey. GELAMM (Grupo de Estudio Latino Americano de Mieloma Múltiple).

The incidence of multiple myeloma (MM) has increased in the last 20 years, particularly in middle and low-middle income countries. Access to diagnostic and prognostic tests and the availability of effective care is highly variable globally. Latin America represents 10% of the world population, distributed in countries of varied size, population, and socio-economic development. In the last decade, great improvements have been made in the diagnosis and treatment of MM. Applying these advances in real life is a challenge in our region. Local data regarding MM standards of care and outcomes are limited. A survey was carried out among hematologists from 15 Latin American countries to describe access to MM diagnostic and prognostic tests and the availability of effective care options. This study provides real-world data for MM in our region, highlighting striking differences between public and private access to essential analyses and therapeutic options.

Analysis of Italian regulations on pathways of care for patients in a vegetative or minimally conscious state.

Different rehabilitation models for persons diagnosed with disorders of consciousness have been proposed in Europe during the last decade. In Italy, the Ministry of Health has defined a national healthcare model, although, to date, there is a lack of information on how this has been implemented at regional level. The INCARICO project collected information on different regional regulations, analysing ethical aspects and mapping care facilities (numbers of beds and medical units) in eleven regional territories. The researchers found a total of 106 laws; differences emerged both between regions and versus the national model, showing that patients with the same diagnosis may follow different pathways of care. An ongoing cultural shift from a treatment-oriented medical approach towards a care-oriented integrated biopsychosocial approach was found in all the welfare and healthcare systems analysed. Future studies are needed to explore the relationship between healthcare systems and the quality of services provided.

EFFICIENCY STUDY OF A LEGe DETECTOR SYSTEM FOR THE ASSESSMENT OF 241Am IN SKULL AT CIEMAT WHOLE BODY COUNTER.

(241)Am incorporation due to an incident or chronic exposure causes an internal dose, which can be evaluated from the total activity of this isotope in the skeleton several months after the intake. For this purpose, it is necessary to perform in vivo measurements of this bone-seeker radionuclide in appropriate counting bone geometries with very low attenuation of surrounded tissue and to extrapolate to total activity in the skeleton (ICRP 89, Basic anatomical and physiological data for use in radiological protection: reference values. 2001. 265). The work here presented refers to direct measurements of americium in the Cohen skull phantom at the CIEMAT Whole Body Counter (WBC) using low-energy germanium (LEGe) detectors inside a shielding room. The main goal was to determinate the most adequate head counting geometry for the in vivo detection of americium in the bone. The calibration of the in vivo LEGe system was performed with four detectors with 2 cm of distance to Cohen phantom. Two geometries were measured, on junction of frontal to parietal bones and frontal bone. The efficiencies are very similar in both geometries, the preferred counting geometry is the most comfortable for the person, with the LEGe detectors in the highest part of the frontal bone, near the junction with the parietal bone, CIEMAT WBC participated in a skull intercomparison exercise organised by WG7 of EURADOS (European Radiation Dosimetry Group e.V.). Efficiencies using three different skull phantoms were obtained. Measurements were performed for different head counting positions, four of them in the plane of symmetry and others over the temporal bone. The detector was placed in parallel with the calibration phantom at a distance of 1 cm. The main gamma emission of (241)Am, 59.5 keV (36 %), was used for comparing efficiency values. The lower efficiency was obtained over the frontal and occipital bones. Measurement with one LEGe detector over the parietal bone is the most efficient. The activity of each skull phantom was calculated using CIEMAT head calibration. Results of the EURADOS intercomparison are presented here for discussion.

THE CHALLENGE OF CIEMAT INTERNAL DOSIMETRY SERVICE FOR ACCREDITATION ACCORDING TO ISO/IEC 17025 STANDARD, FOR IN VIVO AND IN VITRO MONITORING AND DOSE ASSESSMENT OF INTERNAL EXPOSURES.

The accreditation of an Internal Dosimetry Service (IDS) according to ISO/IEC 17025 Standard is a challenge. The aim of this process is to guarantee the technical competence for the monitoring of radionuclides incorporated in the body and for the evaluation of the associated committed effective dose E(50). This publication describes the main accreditation issues addressed by CIEMAT IDS regarding all the procedures involving good practice in internal dosimetry, focussing in the difficulties to ensure the traceability in the whole process, the appropriate calculation of detection limit of measurement techniques, the validation of methods (monitoring and dose assessments), the description of all the uncertainty sources and the interpretation of monitoring data to evaluate the intake and the committed effective dose.

New graphic AUC-based method to estimate overall survival benefit: pomalidomide reanalysis.

WHAT IS KNOWN AND OBJECTIVE: Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)-based method. COMMENT: In the pivotal trial, pomalidomide plus low-dose dexamethasone showed a significant survival benefit over high-dose dexamethasone, with a difference between medians of 4.6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2.6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61.5% of patients for whom the time to event is reliable enough. WHAT IS NEW AND CONCLUSION: This 2-month differential would have major clinical and pharmacoeconomic implications, on both cost-effectiveness studies and on the willingness of the healthcare systems to pay for this treatment.

Implementation and assessment of a fast-track programme to improve communication between primary and specialized care in patients with suspected cancer: how to shorten time between initial symptoms of cancer, diagnosis and initiation of treatment.

PURPOSE: This study aims to asses a cancer fast-track programme (CFP) to shorten the time since a patient with suspicion of cancer is referred by the primary care (PC) physician to the specialized medical team. METHODS: Guidelines for main suspected tumours were designed to help PC physicians to detect and rapidly refer cases to the CFP oncology coordinator, who sent them to the appropriate department to accelerate diagnosis, staging and therapy. All patients analysed in this report were referred from June 2009 to July 2012. RESULTS: A total of 897 suspected cancer cases were submitted and finally 705 were studied. In 205 (29 %) a cancer diagnosis was confirmed within 23 days (median). Therapy was initiated within 46 days after referral (median). Early diagnoses with a potential curative approach were made in 166 (82 %). CONCLUSIONS: This CFP decreased the waiting time for cancer diagnosis, by improving communication between PC physician and specialized care teams. Most patients included in this program could get therapy with curative intent.

Choosing the best plant for the job: a cost-effective assay to prescreen ancient plant remains destined for shotgun sequencing.

DNA extracted from ancient plant remains almost always contains a mixture of endogenous (that is, derived from the plant) and exogenous (derived from other sources) DNA. The exogenous 'contaminant' DNA, chiefly derived from microorganisms, presents significant problems for shotgun sequencing. In some samples, more than 90% of the recovered sequences are exogenous, providing limited data relevant to the sample. However, other samples have far less contamination and subsequently yield much more useful data via shotgun sequencing. Given the investment required for high-throughput sequencing, whenever multiple samples are available, it is most economical to sequence the least contaminated sample. We present an assay based on quantitative real-time PCR which estimates the relative amounts of fungal and bacterial DNA in a sample in comparison to the endogenous plant DNA. Given a collection of contextually-similar ancient plant samples, this low cost assay aids in selecting the best sample for shotgun sequencing.

Sperm DNA integrity and meiotic behavior assessment in an infertile male carrier of a 9qh+++ polymorphism.

Although several reports on male infertility suggest a relationship between chromosome 9 polymorphisms and infertility, the effects on the phenotype have not been extensively reported. In this study, an infertile patient was found to carry a 9qh+++ chromosome. The flow cytometric TUNEL assay and SCD test have been applied to characterize sperm DNA integrity. In order to assess its meiotic behaviour, synapsis, recombination, and aneuploidy, analyses have been also performed. Sperm DNA fragmentation (SDF) was 77.81% and 87% for the TUNEL and SCD tests, respectively. Ninety-two percent of pachytene cells analyzed showed meiotic abnormalities. The mean number of MLH1 foci per pachytene in the control group was higher (49) than the mean found in the 9qh+++ patient (38) (P < .0001). In spermatozoa, significant increases of disomy rates were observed for chromosome 18 and for the sex chromosomes (P < .0001). These disturbances could be present in other male carriers of a less marked 9qh+.

EURADOS intercomparison on measurements and Monte Carlo modelling for the assessment of americium in a USTUR leg phantom.

A collaboration of the EURADOS working group on 'Internal Dosimetry' and the United States Transuranium and Uranium Registries (USTUR) has taken place to carry out an intercomparison on measurements and Monte Carlo modelling determining americium deposited in the bone of a USTUR leg phantom. Preliminary results and conclusions of this intercomparison exercise are presented here.

Comparative assessment of site assignments in CID and electron transfer dissociation spectra of phosphopeptides discloses limited relocation of phosphate groups.

In large scale mass spectrometry-based phosphoproteomics, a current bottleneck is the unambiguous assignment of the phosphorylation site within the peptide. An additional problem is that it has been reported that under conditions wherein peptide ions are collisionally activated the phosphate group may migrate to a nearby phosphate group acceptor, thus causing ambiguity in site assignment. Here, we generated and analyzed a statistically significant number of phosphopeptides. Starting with a human cell lysate, we obtained via strong cation exchange fractionation nearly pure phosphopeptide pools from trypsin and Lys-N digestions. These pools were subjected to nano-LC-MS using an Orbitrap mass spectrometer that is equipped with both CID and electron transfer dissociation with supplemental activation (ETcaD) functionality. We configured a method to obtain sequentially both ETcaD and CID spectra for each peptide ion. We exploited the resistant nature of ETcaD toward rearrangement of phosphate groups to evaluate whether there is potentially phosphate group relocation occurring during CID. We evaluated a number of peptide and spectral annotation properties and found that for ∼75% of the sequenced phosphopeptides the assigned phosphosite was unmistakably identical for both the ETcaD and CID spectra. For the remaining 25% of the sequenced phosphopeptides, we also did not observe evident signs of relocation, but these peptides exhibited signs of ambiguity in site localization, predominantly induced by factors such as poor fragmentation, sequences causing inefficient fragmentation, and generally poor spectrum quality. Our data let us derive the conclusion that both for trypsin- and Lys-N-generated peptides there is little relocation of phosphate groups occurring during CID.

Burden and health-related quality of life of Spanish caregivers of persons with multiple sclerosis.

Little information exists about caregivers of persons with multiple sclerosis (MS). Our aims were to describe the characteristics of a sample of caregivers of persons with MS, assess their perceived burden, health-related quality of life, and investigate factors influencing this burden. We studied 278 caregivers of persons with MS, recruited from a Spanish cross-sectional survey, measuring health-related quality of life by the 36-Item Short-Form Health Survey (SF-36) and burden by the Zarit Caregiver Burden Interview. Of the caregivers, 56.8% were female and their mean age was 50.1 +/- 12.6 years. Their main relationship with the person with MS was spouse/partner (52.9%) and son or daughter (25.9%). Caregiver General Health, Mental Health, Bodily Pain, and Role-emotional Functioning were the most affected dimensions on the SF-36. Multiple regression analysis showed that independent and significant predictors of burden were Role-emotional Functioning and Vitality dimensions SF-36 scores of caregivers, and the Expanded Disability Status Scale scores. The total adjusted variance explained by these variables (adjusted R(2)) was 0.512. Emotional factors and the disability of the person with MS were major predictors of burden. Psychological and social support should be considered to reduce caregiver burden.

Assessment of the internal dose of 241Am in bone by in vivo measurements of activity deposited in knee.

In case of chronic exposure or long time after an acute intake of (241)Am as a consequence of an incident, the assessment of internal dose might be realised by estimating the total activity content of this element in the skeleton. For this purpose, a new methodology has been developed at the Whole Body Counting Laboratory of CIEMAT. In vivo measurements of this bone-seeker radionuclide in the knee are performed using four low energy germanium detectors inside a shielded room. The sensitivity study of this technique resulted in a minimum detectable activity of 7 Bq, for a counting time of 1800 s. Extrapolation to the total activity in the bone has been carried out by taking into account that the bone content of the knee calibration phantom is equivalent to 10.7% of the whole skeleton mass. The results of in vivo measurements of population and the procedure for internal dose evaluation are presented here.

Monte Carlo based voxel phantoms for in vivo internal dosimetry.

The purpose of this communication is to describe briefly the computer programs developed to generate the MCNP input file corresponding to any segmented tomographic data and its application to the calibration procedures for in vivo internal dosimetry. The method has been applied to the determination of 241Am in bone by measurement in skull and knee using MCNP voxel models of a real human head and knee based on the tomographic Voxelman and Arms Down phantoms developed by Zubal et al. at Yale University.

Assessment of the efficacy of Artemia sp (Crustacea) cysts chorion as barrier to chlorpyrifos (organophosphorus pesticide) exposure. Effect on hatching and survival.

In order to reveal the efficacy of the Artemia cysts chorion as barrier to the organophosphorus pesticide chlorpyrifos, whole and decapsulated cysts have been exposed to 10 mg L(-1) chlorpyrifos in sea water during hydration and hatching phase, separately. The concentration of chlorpyrifos in capsulated and decapsulated cysts after exposure has been determined in order to elucidate the efficacy of chorion as protection to the embryo. The results obtained demonstrate the ability of the cysts chorion to obstruct the pass of chlorpyrifos molecules through this protection structure. Thus, the concentration of chlorpyrifos in exposed decapsulated cysts is higher than in exposed whole cysts. Moreover, after removing the chorion of exposed cysts, the concentration of chlorpyrifos in the embryo was lower than that of cysts exposed, what would demonstrate the retention of chlorpyrifos molecules by the shell. Hatching was not severely affected by exposure to the insecticide whereas survival at 44 h of the nauplii exposed to chlorpyrifos was significantly different from the controls. Survival of nauplii hatched from exposed decapsulated cysts was higher than that from those hatched from exposed whole cysts, probably because of the lower vitality of the latter, due to depletion of energy reserves during hatching.

Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic liver transplantation with portal vein arterialization in pigs.

OBJECTIVE: Our aim was to evaluate liver graft integrity and function using scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA). MATERIALS AND METHODS: Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal echogenicity, portal and arterial anatomy, and portal and biliary system flow. Two types of scintigraphy were performed: microaggregated human albumin colloid scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both labeled with 99mTc. RESULTS: The animals were distributed into two groups. The first group consisted of three animals with clinical suspicion of graft dysfunction, in which the ultrasonographic study revealed areas of parenchymal destructuring. In the scintigraphic study, heterogenous uptake was observed; there was no uptake in one animal. Necropsy of these three animals revealed areas of graft necrosis. The second group consisted of five animals with good clinical evolutions, in which the ultrasonographic study showed portal dilation, portal flow with arterial spiculations, and homogenous echogenicity of the hepatic parenchyma. The scintigraphic study revealed homogenous uptake by the graft and an elimination speed of the hepatobiliary agent similar to that of the native liver. CONCLUSIONS: An heterogenous echostructure of the graft provided a sign of poor prognosis indicating necrosis in the same way as heterogenous uptake or nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to evaluate biliary function and bile elimination. In an AHLT-PVA, the main ultrasound findings derived from arterialization were dilation of the portal system and portal flow with arterial spiculations.