Genetic variability of the mTOR pathway and prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)

The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (ORallele = 0.85, 95% CI 0.78–0.94, p = 1.3×10−3 for rs546950 and ORallele = 0.84, 95% CI 0.76–0.93, p = 5.6×10−4 for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.

Effectiveness of a nurse-led case management home care model in Primary Health Care. A quasi-experimental, controlled, multi-centre study

Background Demand for home care services has increased considerably, along with the growing complexity of cases and variability among resources and providers. Designing services that guarantee co-ordination and integration for providers and levels of care is of paramount importance. The aim of this study is to determine the effectiveness of a new case-management based, home care delivery model which has been implemented in Andalusia (Spain). Methods Quasi-experimental, controlled, non-randomised, multi-centre study on the population receiving home care services comparing the outcomes of the new model, which included nurse-led case management, versus the conventional one. Primary endpoints: functional status, satisfaction and use of healthcare resources. Secondary endpoints: recruitment and caregiver burden, mortality, institutionalisation, quality of life and family function. Analyses were performed at base-line, and at two, six and twelve months. A bivariate analysis was conducted with the Student's t-test, Mann-Whitney's U, and the chi squared test. Kaplan-Meier and log-rank tests were performed to compare survival and institutionalisation. A multivariate analysis was performed to pinpoint factors that impact on improvement of functional ability. Results Base-line differences in functional capacity – significantly lower in the intervention group (RR: 1.52 95%CI: 1.05–2.21; p = 0.0016) – disappeared at six months (RR: 1.31 95%CI: 0.87–1.98; p = 0.178). At six months, caregiver burden showed a slight reduction in the intervention group, whereas it increased notably in the control group (base-line Zarit Test: 57.06 95%CI: 54.77–59.34 vs. 60.50 95%CI: 53.63–67.37; p = 0.264), (Zarit Test at six months: 53.79 95%CI: 49.67–57.92 vs. 66.26 95%CI: 60.66–71.86 p = 0.002). Patients in the intervention group received more physiotherapy (7.92 CI95%: 5.22–10.62 vs. 3.24 95%CI: 1.37–5.310; p = 0.0001) and, on average, required fewer home care visits (9.40 95%CI: 7.89–10.92 vs.11.30 95%CI: 9.10–14.54). No differences were found in terms of frequency of visits to A&E or hospital re-admissions. Furthermore, patients in the control group perceived higher levels of satisfaction (16.88; 95%CI: 16.32–17.43; range: 0–21, vs. 14.65 95%CI: 13.61–15.68; p = 0,001). Conclusion A home care service model that includes nurse-led case management streamlines access to healthcare services and resources, while impacting positively on patients' functional ability and caregiver burden, with increased levels of satisfaction.

Variability of indication criteria in knee and hip replacement: an observational study

BACKGROUND. Total knee (TKR) and hip (THR) replacement (arthroplasty) are effective surgical procedures that relieve pain, improve patients' quality of life and increase functional capacity. Studies on variations in medical practice usually place the indications for performing these procedures to be highly variable, because surgeons appear to follow different criteria when recommending surgery in patients with different severity levels. We therefore proposed a study to evaluate inter-hospital variability in arthroplasty indication. METHODS. The pre-surgical condition of 1603 patients included was compared by their personal characteristics, clinical situation and self-perceived health status. Patients were asked to complete two health-related quality of life questionnaires: the generic SF-12 (Short Form) and the specific WOMAC (Western Ontario and Mcmaster Universities) scale. The type of patient undergoing primary arthroplasty was similar in the 15 different hospitals evaluated.The variability in baseline WOMAC score between hospitals in THR and TKR indication was described by range, mean and standard deviation (SD), mean and standard deviation weighted by the number of procedures at each hospital, high/low ratio or extremal quotient (EQ5-95), variation coefficient (CV5-95) and weighted variation coefficient (WCV5-95) for 5-95 percentile range. The variability in subjective and objective signs was evaluated using median, range and WCV5-95. The appropriateness of the procedures performed was calculated using a specific threshold proposed by Quintana et al for assessing pain and functional capacity. RESULTS. The variability expressed as WCV5-95 was very low, between 0.05 and 0.11 for all three dimensions on WOMAC scale for both types of procedure in all participating hospitals. The variability in the physical and mental SF-12 components was very low for both types of procedure (0.08 and 0.07 for hip and 0.03 and 0.07 for knee surgery patients). However, a moderate-high variability was detected in subjective-objective signs. Among all the surgeries performed, approximately a quarter of them could be considered to be inappropriate. CONCLUSIONS. A greater inter-hospital variability was observed for objective than for subjective signs for both procedures, suggesting that the differences in clinical criteria followed by surgeons when indicating arthroplasty are the main responsible factors for the variation in surgery rates.

Impactia: automating the study of the scientific production

Introduction The Andalusian Public Health System Virtual Library (Biblioteca Virtual del Sistema Sanitario Público de Andalucía, BV-SSPA) was set up in June 2006. It consists of a regional government action with the aim of democratizing the health professional access to quality scientific information, regardless of the professional workplace. Andalusia is a region with more than 8 million inhabitants, with 100,000 health professionals for 41 hospitals, 1,500 primary healthcare centres, and 28 centres for non-medical attention purposes (research, management, and educational centres). Objectives The Department of Development, Research and Investigation (R+D+i) of the Andalusian Regional Government has, among its duties, the task of evaluating the hospitals and centres of the Andalusian Public Health System (SSPA) in order to distribute its funding. Among the criteria used is the evaluation of the scientific output, which is measured using bibliometry. It is well-known that the bibliometry has a series of limitations and problems that should be taken into account, especially when it is used for non-information sciences, such us career, funding, etc. A few years ago, the bibliometric reports were done separately in each centre, but without using preset and well-defined criteria, elements which are basic when we need to compare the results of the reports. It was possible to find some hospitals which were including Meeting Abstracts in their figures, while others do not, and the same was happening with Erratum and many other differences. Therefore, the main problem that the Department of R+D+i had to deal with, when they were evaluating the health system, was that bibliometric data was not accurate and reports were not comparable. With the aim of having an unified criteria for the whole system, the Department of R+D+i ordered the BV-SSPA to do the year analysis of the scientific output of the system, using some well defined criteria and indicators, among whichstands out the Impact Factor. Materials and Methods As the Impact Factor is the bibliometric indicator that the virtual library is asked to consider, it is necessary to use the database Web of Science (WoS), since it is its owner and editor. The WoS includes the databases Science Citation Index (SCI), Social Sciences Citation Index (SSCI) and Arts & Humanities Citation Index. To gather all the documents, SCI and SSCI are used; to obtain the Impact Factor and quartils, it is used the Journal Citation Reports, JCR. Unlike other bibliographic databases, such us MEDLINE, the bibliometric database WoS includes the address of all the authors. In order to retrieve all the scientific output of the SSPA, we have done general searches, which are afterwards processed by a tool developed by our library. We have done nine different searches using the field ‘address’; eight of them including ‘Spain’ and each one of the eight Andalusian Regions, and the other one combining ‘Spain’ with all those cities where there are health centres, since we have detected that there are some authors that do not use the region in their signatures. These are some of the search strategies: AD=Malaga and AD=Spain AD=Sevill* and AD=Spain AD=SPAIN AND (AD=GUADIX OR AD=BAZA OR AD=MOTRIL) Further more, the field ‘year’ is used to determine the period. To exploit the data, the BV-SSPA has developed a tool called Impactia. It is a web application which uses a database to store the information of the documents generated by the SSPA. Impactia allows the user to automatically process the retrieved documents, assigning them to their correspondent centres. In order to do the classification of documents automaticaly, it was necessary to detect the huge variability of names of the centres that the authors use in their signatures. Therefore, Impactia knows that if an author signs as “Hospital Universitario Virgen Macarena”, “HVM” or “Hosp. Virgin Macarena”, he belongs to the same centre. The figure attached shows the variability found for the Empresa Publica Hospital de Poniente. Besides the documents from WoS, Impactia includes the documents indexed in Scopus and in other databases, where we do bibliographic searches using similar strategies to the later ones. Aware that in the health centres and hospitals there is a lot of grey literature that is not gathered in databases, Impactia allows the centres to feed the application with these documents, so that all the SSPA scientific output is gathered and organised in a centralized place. The ones responsible of localizing this gray literature are the librarians of each one of the centres. They can also do statements to the documents and indicators that are collected and calculated by Impactia. The bulk upload of documents from WoS and Scopus into Impactia is monthly done. One of the main issues that we found during the development of Impactia was the need of dealing with duplicated documents obtained from different sources. Taking into account that sometimes titles might be written differently, with slashes, comas, and so on, Impactia detects the duplicates using the field ‘DOI’ if it is available or comparing the fields: page start, page end and ISSN. Therefore it is possible to guarantee the absence of duplicates. Results The data gathered in Impactia becomes available to the administrative teams and hospitals managers, through an easy web page that allows them to know at any moment, and with just one click, the detailed information of the scientific output of their hospitals, including useful graphs such as percentage of document types, journals where their scientists usually publish, annual comparatives, bibliometric indicators and so on. They can also compare the different centres of the SSPA. Impactia allows the user to download the data from the application, so that he can work with this information or include them in their centres’ reports. This application saves the health system many working hours. It was previously done manually by forty one librarians, while now it is done by only one person in the BV-SSPA during two days a month. To sum up, the benefits of Impactia are: It has shown its effectiveness in the automatic classification, treatment and analysis of the data. It has become an essential tool for all managers to evaluate quickly and easily the scientific production of their centers. It optimizes the human resources of the SSPA, saving time and money. It is the reference point for the Department of R+D+i to do the scientific health staff evaluation.

Clinical audit of COPD patients requiring hospital admissions in Spain: AUDIPOC study.

BACKGROUNDS AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines. The present study describes hospital resources, hospital factors related to case recruitment variability, patients' characteristics, and adherence to guidelines. METHODOLOGY/PRINCIPAL FINDINGS An organisational database was completed by all participant hospitals recording resources and organisation. Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified. At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population. Audited patients were reassessed 90 days after admission for survival and readmission rates. A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death. Median inpatient mortality was 5% (across-hospital range 0-35%). Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%). The overall mortality rate was 11.6% (0-50%). Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment. Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles. CONCLUSIONS/SIGNIFICANCE The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes. The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement.

Infornut® Process; improves accessibility to diagnosis and nutritional support for the malnourished hospitalized patient; impact on management indicators; two-year assessment.

Introduction: The high prevalence of disease-related hospital malnutrition justifies the need for screening tools and early detection in patients at risk for malnutrition, followed by an assessment targeted towards diagnosis and treatment. At the same time there is clear undercoding of malnutrition diagnoses and the procedures to correct it Objectives: To describe the INFORNUT program/ process and its development as an information system. To quantify performance in its different phases. To cite other tools used as a coding source. To calculate the coding rates for malnutrition diagnoses and related procedures. To show the relationship to Mean Stay, Mortality Rate and Urgent Readmission; as well as to quantify its impact on the hospital Complexity Index and its effect on the justification of Hospitalization Costs. Material and methods: The INFORNUT® process is based on an automated screening program of systematic detection and early identification of malnourished patients on hospital admission, as well as their assessment, diagnoses, documentation and reporting. Of total readmissions with stays longer than three days incurred in 2008 and 2010, we recorded patients who underwent analytical screening with an alert for a medium or high risk of malnutrition, as well as the subgroup of patients in whom we were able to administer the complete INFORNUT® process, generating a report for each.

Clinical intervals and diagnostic characteristics in a cohort of prostate cancer patients in Spain: a multicentre observational study.

BACKGROUND Little is known about the healthcare process for patients with prostate cancer, mainly because hospital-based data are not routinely published. The main objective of this study was to determine the clinical characteristics of prostate cancer patients, the, diagnostic process and the factors that might influence intervals from consultation to diagnosis and from diagnosis to treatment. METHODS We conducted a multicentre, cohort study in seven hospitals in Spain. Patients' characteristics and diagnostic and therapeutic variables were obtained from hospital records and patients' structured interviews from October 2010 to September 2011. We used a multilevel logistic regression model to examine the association between patient care intervals and various variables influencing these intervals (age, BMI, educational level, ECOG, first specialist consultation, tumour stage, PSA, Gleason score, and presence of symptoms) and calculated the odds ratio (OR) and the interquartile range (IQR). To estimate the random inter-hospital variability, we used the median odds ratio (MOR). RESULTS 470 patients with prostate cancer were included. Mean age was 67.8 (SD: 7.6) years and 75.4 % were physically active. Tumour size was classified as T1 in 41.0 % and as T2 in 40 % of patients, their median Gleason score was 6.0 (IQR:1.0), and 36.1 % had low risk cancer according to the D'Amico classification. The median interval between first consultation and diagnosis was 89 days (IQR:123.5) with no statistically significant variability between centres. Presence of symptoms was associated with a significantly longer interval between first consultation and diagnosis than no symptoms (OR:1.93, 95%CI 1.29-2.89). The median time between diagnosis and first treatment (therapeutic interval) was 75.0 days (IQR:78.0) and significant variability between centres was found (MOR:2.16, 95%CI 1.45-4.87). This interval was shorter in patients with a high PSA value (p = 0.012) and a high Gleason score (p = 0.026). CONCLUSIONS Most incident prostate cancer patients in Spain are diagnosed at an early stage of an adenocarcinoma. The period to complete the diagnostic process is approximately three months whereas the therapeutic intervals vary among centres and are shorter for patients with a worse prognosis. The presence of prostatic symptoms, PSA level, and Gleason score influence all the clinical intervals differently.