In the last decades, Housing First model has become a feasible alternative to the traditional “staircase” systems in caring for the most vulnerable homeless people. The analysis that we present in ...this work is referred to Hábitat, a pioneering HF programme in Spain, which has been evaluated attending to both costs and outcomes. A randomised controlled trial was carried out and the collected data was explored through a Cost‐Effectiveness Analysis (CEA), including the estimation of Incremental Cost‐Effectiveness Ratios (ICER) and acceptability thresholds of the programme's spending. The results highlight the capacity of the programme to significantly improve the participants' life satisfaction levels, reduce the number of homeless nights, and increase the rate of institutional coverage. Even though the programme involves significant short‐term expenditure on accommodation, positive effects in net terms are demonstrated supporting the usefulness and viability of HF model.
Background
Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized ...treatments and improvement of therapeutic outcomes.
Methods
Forty‐six paraffin tumor samples from ASCC patients were analyzed by whole‐exome sequencing. Copy number variants (CNVs) were identified and their relation to disease‐free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors.
Results
On the discovery cohort, the median age was 61 years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33 months, and overall survival was 45 months. Twenty‐nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5 years than those with two CYP2D6 copies (21% vs. 84%; p < .0002, hazard ratio HR, 5.8; 95% confidence interval CI, 2.7–24.9). In the GEMCAD validation cohort, patients with CYP2D6 CNV also had worse DFS at 5 years (56% vs. 87%; p = .02, HR = 3.6; 95% CI, 1.1–5.7). Mitochondria and mitochondrial cell‐cycle proteins were overexpressed in patients with CYP2D6 CNV.
Conclusions
Tumor CYP2D6 CNV identified patients with a significantly worse DFS at 5 years among localized ASCC patients treated with 5‐fluorouracil, mitomycin C, and radiotherapy. Proteomics pointed out mitochondria and mitochondrial cell‐cycle genes as possible therapeutic targets for these high‐risk patients.
Plain Language Summary
Anal squamous cell carcinoma is an infrequent tumor whose treatment has not been changed since the 1970s.
However, disease‐free survival in late staged tumors is between 40% and 70%.
The presence of an alteration in the number of copies of CYP2D6 gene is a biomarker of worse disease‐free survival.
The analysis of the proteins in these high‐risk patients pointed out mitochondria and mitochondrial cell‐cycle genes as possible therapeutic targets.
Therefore, the determination of the number of copies of CYP2D6 allows the identification of anal squamous carcinoma patients with a high‐risk of relapse that could be redirected to a clinical trial.
Additionally, this study may be useful to suggest new treatment strategies to increase current therapy efficacy.
The presence of a copy number variant in CYP2D6 gene in localized anal squamous cell carcinoma tumors is a biomarker of worse disease‐free survival. Proteomics pointed out mitochondria and mitochondrial cell‐cycle genes as possible targets for these high‐risk patients.
In 2014, a non-governmental organization called HOGAR SÍ initiated the Hábitat program as a pioneer attempt to implement the Housing First model in Spain. The present study is part of the evaluation ...of this program, which was carried out from May 2015 to February 2020 using a form of a randomized controlled trial. The treatment group was compared with a control group (people experiencing homelessness but not selected as Hábitat users), keeping track of their evolution over 18 months. Among the many dimensions that were evaluated (coverage of basic needs, life satisfaction, victimization, physical and mental health, etc.), the study analyzed social support and leisure activities involving the use of mobile media and other communication technologies—along similar lines to some previous research. The main results show that participating in the Hábitat program brought a few improvements in digital inclusion. That is the case of the higher use of mobile phones to receive calls, to connect to the Internet, or to have contact with relatives, partners, or friends. These gains seem to be significant for the increase in perception of available social support by Hábitat users, whereas these changes did not occur in the comparison group to the same extent. Additionally, participating in the program enhances satisfaction with leisure time, as well as the frequency of carrying out some activities such as shopping, watching TV, or doing a pastime or hobby. It could be concluded that the Hábitat program achieved significant improvements in areas beyond specific housing services. The positive effects regarding social support and leisure activities seem to be partly channeled through mobile phones and digital applications; nevertheless, we are aware that further research and discussion on the active role of these technologies in helping people experiencing homelessness is still necessary.
Aunque el Patrimonio Cultural es fuente reconocida de bienestar, su sobreexplotación turística genera fuertes impactos negativos, agravados en las grandes ciudades por la concentración de efectos en ...el espacio. Este trabajo aborda el caso de Madrid, ciudad que cuenta en su periferia metropolitana con activos patrimoniales de primer nivel, cuyo mejor aprovechamiento turístico ayudaría a mitigar el impacto negativo en la capital, a la vez que contribuiría al desarrollo económico y social de la periferia. En la investigación se aplicó un planteamiento metodológico dinámico con cuatro planos de análisis complementarios: documental y de redes, cualitativo, cuantitativo y procesos participativos. Los resultados evidencian la necesidad de adoptar estrategias de gestión cultural y de planificación turística orientadas al reequilibrio de los flujos de visitantes. La activación de los propios vecinos se revela como un recurso especialmente valioso para fortalecer un turismo de proximidad, experiencial y más sostenible. El impacto de la Covid-19, por una parte, y la declaración del Paseo del Prado y el Retiro como Patrimonio de la Humanidad, por otra, han puesto aún más de actualidad esta situación.
Depression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly ...associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = 0.65, 0.76). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesity-associated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals.
En las últimas tres décadas la metodología Housing First se ha extendido desde Norteamérica a otros países. En 2014 se puso en marcha en España —cuando el país todavía estaba sumido en una profunda ...crisis económica— el programa Hábitat siguiendo ese modelo. Este estudio forma parte de la evaluación socioeconómica llevada a cabo entre 2015 y 2020 mediante un ensayo controlado aleatorizado. El grupo de tratamiento se comparó con un grupo de control haciendo un seguimiento de su evolución a lo largo de 18 meses. Comprobamos que logró mejoras significativas en la mayoría de áreas analizadas, más allá de los servicios específicos de vivienda. Respecto a los costes, resulta evidente que el programa supone una gran inversión en términos de vivienda, pero consigue compensar algunos gastos en otros apartados y, sobre todo, genera mejoras muy valiosas en las personas participantes. Para finalizar nuestro artículo, discutimos el alcance de estos resultados y reflexionamos sobre las limitaciones a superar en próximas evaluaciones de intervenciones similares.
In the predictD-intervention, GPs used a personalised biopsychosocial programme to prevent depression. This reduced the incidence of major depression by 21.0%, although the results were not ...statistically significant.
To determine whether the predictD-intervention is effective at preventing anxiety in primary care patients without depression or anxiety.
Secondary study of a cluster randomised trial with practices randomly assigned to either the predictD-intervention or usual care. This study was conducted in seven Spanish cities from October 2010 to July 2012.
In each city, 10 practices and two GPs per practice, as well as four to six patients every recruiting day, were randomly selected until there were 26-27 eligible patients for each GP. The endpoint was cumulative incidence of anxiety as measured by the PRIME-MD screening tool over 18 months.
A total of 3326 patients without depression and 140 GPs from 70 practices consented and were eligible to participate; 328 of these patients were removed because they had an anxiety syndrome at baseline. Of the 2998 valid patients, 2597 (86.6%) were evaluated at the end of the study. At 18 months, 10.4% (95% CI = 8.7% to 12.1%) of the patients in the predictD-intervention group developed anxiety compared with 13.1% (95% CI = 11.4% to 14.8%) in the usual-care group (absolute difference = -2.7% 95% CI = -5.1% to -0.3%;
= 0.029).
A personalised intervention delivered by GPs for the prevention of depression provided a modest but statistically significant reduction in the incidence of anxiety.
Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to ...reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care.
Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months.
With a willingness-to-pay threshold of €10,000 (£8568) the probability of cost-effectiveness oscillated from 83% (societal perspective) to 89% (health perspective). If the threshold was increased to €30,000 (£25,704), the probability of being considered cost-effective was 94% (societal perspective) and 96%, respectively (health perspective). The sensitivity analysis confirmed these results.
Compared with usual care, an intervention based on personal predictors of risk of depression implemented by GPs is a cost-effective strategy to prevent depression. This type of personalized intervention in primary care should be further developed and evaluated.
ClinicalTrials.gov, NCT01151982. Registered on June 29, 2010.
Surgical units attending sarcomas in Spain are poor studied. The aim is to know the management of this pathology to identify areas of improvement through multicenter study based on a voluntary ...survey. The survey was completed by 74 surgeons of different hospitals, which 32,4% is exclusively dedicated to sarcomas. Only 24.3% declared to receive specific training in sarcomas. The most frequent type of hospital was the third level (56.8%), where 38,1% of the surgeons belong to societies or working-groups in sarcoma fields vs. 9,4% in first-second levels. The number of surgeons with specific theoretical training and papers published in this field are higher in third level hospitals. 55,4% belonged to a multidisciplinary unit. A multidisciplinary team was available in 57% of third level hospital vs 28% in others. Most services in charge of this patients are characterized by deficient specialization, low workload and the absence of a multidisciplinary team.
The predictD intervention, a multicomponent intervention delivered by family physicians (FPs), reduced the incidence of major depression by 21% versus the control group and was cost-effective. A ...qualitative methodology was proposed to identify the mechanisms of action of these complex interventions.
To seek the opinions of these FPs on the potential successful components of the predictD intervention for the primary prevention of depression in primary care and to identify areas for improvement.
Qualitative study with FPs who delivered the predictD intervention at 35 urban primary care centres in seven Spanish cities. Face-to-face semi-structured interviews adopting a phenomenological approach. The data was triangulated by three investigators using thematic analysis and respondent validation was carried out.
Sixty-seven FPs were interviewed and they indicated strategies used to perform the predictD intervention, including specific communication skills such as empathy and the activation of patient resources. They perceived barriers such as lack of time and facilitators such as prior acquaintance with patients. FPs recognized the positive consequences of the intervention for FPs, patients and the doctor-patient relationship. They also identified strategies for future versions and implementations of the predictD intervention.
The FPs who carried out the predictD intervention identified factors potentially associated with successful prevention using this program and others that could be improved. Their opinions about the predictD intervention will enable development of a more effective and acceptable version and its implementation in different primary health care settings.