Nigral and striatal connectivity alterations in asymptomatic LRRK2 mutation carriers: A magnetic resonance imaging study

Background. The study of the functional connectivity by means of magnetic resonance imaging (MRI) in asymptomatic LRRK2 mutation carriers could contribute to the characterization of the prediagnostic phase of LRRK2 associated Parkinson's disease (PD). Objective. To characterize MRI functional patterns during resting state in asymptomatic LRRK2 mutation carriers. Methods. We acquired structural and functional MRI data of 18 asymptomatic LRRK2 mutation carriers and 18 asymptomatic LRRK2 mutation noncarriers, all first-degree relatives of LRRK2-PD patients. Starting from resting state data, we analyzed the functional connectivity of the striatocortical and the nigrocortical circuitry. Structural brain data was analyzed by voxel based morphometry, cortical thickness and volumetric measures. Results: Asymptomatic LRRK2 mutation carriers had functional connectivity reductions between the caudal motor part of the left striatum and ipsilateral precuneus and superior parietal lobe. Connectivity in these regions correlated with subcortical gray matter volumes in mutation carriers. Asymptomatic carriers also showed increased connectivity between the right substantia nigra and bilateral occipital cortical regions (occipital pole and cuneus bilaterally, and right lateral occipital cortex). No intergroup differences in structural MRI measures were found. In LRRK2 mutation carriers, age and functional connectivity correlated negatively with striatal volumes. Additional analyses including only subjects with the G2019S mutation revealed similar findings. Conclusion: Asymptomatic LRRK2 mutation carriers showed functional connectivity changes in striatocortical and nigrocortical circuits compared with noncarriers. These findings support the concept that altered brain connectivity precedes the onset of classical motor features in a genetic form of PD

Adaptation and validation of the Spanish version of the patient-oriented prostate utility scale (PORPUS)

Objective: the Patient-Oriented Prostate Utility Scale (PORPUS) is a combined profile and utility-based quality of life measure for prostate cancer patients. Our objectives were to adapt the PORPUS into Spanish and to assess its acceptability, reliability, and validity. Methods: the PORPUS was adapted into Spanish using forward and back translations and cognitive debriefing. PORPUS was administered jointly with the SF-36 and the Expanded Prostate Index Composite (EPIC) to 480 Spanish prostate cancer patients treated with radical prostatectomy or radiotherapy. The Spanish PORPUS scores' distribution and reliability were examined and compared with the original instrument. To evaluate construct validity, relationships were assessed between PORPUS and other instruments (testing hypotheses of the original PORPUS study), and among known groups defined by side effect severity. Results: reliability coefficient was 0.76 (similar to the original PORPUS' 0.81). Spanish PORPUS items presented correlations ranging 0.57-0.88 with the corresponding EPIC domains, as in the original PORPUS study (0.60-0.83). Both PORPUS-P and PORPUS-U showed significant differences and large effect sizes (0.94-1.90) when comparing severe versus no problem groups on urinary, bowel, sexual and hormonal side effects defined by EPIC. Conclusions: a conceptually equivalent Spanish version was obtained, with high reliability and good construct validity, similar to the original Canadian PORPUS version. It can therefore be used to measure health-related quality of life and utilities in Spanish prostate cancer patients

Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers

Objective: In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC). Methods: A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD. Results: Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC. Conclusions: Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD

Quality of life impact of primary treatments for localized prostate cancer patients without hormonal treatment

Purpose Earlier studies evaluating the effect on quality of life (QoL) of localized prostate cancer interventions included patients receiving adjuvant hormone therapy, which could have affected their outcomes. Our objective was to compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment. PATIENTS AND METHODS: This was a prospective study of 435 patients treated with radical prostatectomy, external-beam radiotherapy, or brachytherapy. QoL was assessed before and after treatment with the Short Form-36 and the Expanded Prostate Cancer Index Composite. Differences between groups were tested by analysis of variance. Distribution of outcome at 3 years was examined by stratifying according to baseline status. Generalized estimating equation models were constructed to assess the effect of treatment over time. RESULTS: Compared with the brachytherapy group, the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results (-18.22, -13.19, and +6.38, respectively, at 3 years; P < .001). In patients with urinary irritative-obstructive symptoms at baseline, improvement was observed in 64% of those treated with nerve-sparing radical prostatectomy. Higher bowel worsening (-2.87, P = .04) was observed in the external radiotherapy group, with 20% of patients reporting bowel symptoms. CONCLUSION: Radical prostatectomy caused urinary incontinence and sexual dysfunction but improved pre-existing urinary irritative-obstructive symptoms. External radiotherapy and brachytherapy caused urinary irritative-obstructive adverse effects and some sexual dysfunction. External radiotherapy also caused bowel adverse effects. Relevant differences between treatment groups persisted for up to 3 years of follow-up, although the difference in sexual adverse effects between brachytherapy and prostatectomy tended to decline over long-term follow-up. These results provide valuable information for clinical decision making

Early experience and quality of life in SBRT prostate cancer boost of 9 Gy in a phase II trial

Purpose or ObjectiveExtracranial stereotactic body radiation therapy (SBRT) allows delivering high doses per fraction with high accuracy to the prostatic gland in a low number of fractions.Dose escalation in normofractionaded radiation prostate cancer trials showed an increased toxicity.In order to evaluate the feasibility and toxicity of a regimen of a single dose hypofractionated prostate stereotactic boost a phase II study was undertaken. Self-reported quality of life (QOL) measures were also obtained in order to better define the possible deleterious effect of treatment

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with I-125 brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan-Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making. Study identifier at ClinicalTrials.gov: NCT01492751

Comparación de costes de tres tratamientos del cáncer de próstata localizado en España : prostatectomía radical, braquiterapia prostática y radioterapia conformacional externa 3D

Altres ajuts: AATM/086/24/2000Objetivo: comparar los costes de los tratamientos más establecidos para el cáncer de próstata localizado según grupos de riesgo, edad y comorbilidad, desde la perspectiva del proveedor asistencial. Métodos: comparación de costes en pacientes reclutados consecutivamente entre 2003 y 2005 en una unidad funcional de tratamiento del cáncer de próstata. La utilización de servicios hasta 6 meses después del inicio del tratamiento se obtuvo de las bases de datos hospitalarias, y los costes directos se estimaron mediante cálculo microcoste. La información sobre las características clínicas de los pacientes y los tratamientos recogió prospectivamente. Los costes se compararon mediante tests no paramétricos de comparación de medianas (Kruskall-Wallis) y un modelo semilogarítmico de regresión múltiple. Resultados: la diferencia de costes fue estadísticamente significativa: medianas de 3229.10D, 5369.00Dy 6265.60D para los pacientes tratados con radioterapia conformacional externa 3D, braquiterapia, y prostatectomía radical retro pública, respectivamente (p <0,001). En el análisis multivariado (R2 ajustada=0,8), los costes medios de la braquiterapia y de la radioterapia externa fueron significativamente menores que los de la prostatectomía (coeficiente -0,212 y -0,729, respectivamente). Conclusiones: la prostatectomía radical resultó ser la opción terapéutica de mayor coste. En general, los costes estimados en nuestro estudio son inferiores a los publicados en otros ámbitos. La opción terapéutica explica gran parte de los costes, y tanto la comorbilidad como el grupo de riesgo no mostraron efecto independiente del tratamiento sobre los costes totales.Objective: To compare the initial costs of the three most established treatments for clinically localized prostate cancer according to risk, age and comorbidity groups, from the healthcare provider's perspective. Methods: We carried out a cost comparison study in a sample of patients consecutively recruited between 2003 and 2005 from a functional unit for prostate cancer treatment in Catalonia (Spain). The use of services up to 6 months after the treatment start date was obtained from hospital databases and direct costs were estimated by micro-cost calculation. Information on the clinical characteristics of patients and treatments was collected prospectively. Costs were compared by using nonparametric tests comparing medians (Kruskall-Wallis) and a semi-logarithmic multiple regression model. Results: Among the 398 patients included, the cost difference among treatments was statistically significant: medians were €3,229.10, €5,369.00 and €6,265.60, respectively, for the groups of patients treated with external 3D conformal radiotherapy, brachytherapy and radical retropublic prostatectomy, (p<0.001). In the multivariate analysis (adjusted R=0.8), the average costs of brachytherapy and external radiotherapy were significantly lower than that of prostatectomy (coefficient -0.212 and -0.729, respectively). Conclusions: Radical prostatectomy proved to be the most expensive treatment option. Overall, the estimated costs in our study were lower than those published elsewhere. Most of the costs were explained by the therapeutic option and neither comorbidity nor risk groups showed an effect on total costs independent of treatment

The Notijoves project : Protocol for a randomized controlled trial about new communication technologies and gamification to promote partner notification of sexually transmitted infections among young people

Background: An increase in sexually transmitted infections (STIs) as well as an increase in the use of new information and communication technologies among young people in Catalonia is the inspiration behind the idea of designing a smartphone app to promote partner notification of STIs. Objective: The main objective of this study is to design a Web-based tool adapted to smartphones for partner notification of STIs among youth who are 16 to 24 years old. Additionally, the objective is to evaluate the Web-based tool's role in increasing the patient referral partner notification. Methods: This is a multicenter randomized controlled trial with a proportional stratification of the sample by center and random allocation of participants to the 3 arms of the study (simple Web-based intervention, game Web-based intervention, and control). This study is being conducted by midwives, gynecologists, and physicians in the sexual and reproductive areas of the primary health care centers. Results: The primary outcome measure is the number and proportion of partner notifications. Additional outcome measures are the yield of early diagnosis and treatment of those exposed and infected, acceptability, barriers, and preferences for partner notification. Expected results include an increase in the yield of partner notification, early diagnosis and treatment among youth using Web-based interventions compared with those receiving the traditional advice to notify, and a description of sexual networks among those participating in the study. Conclusions: The Notijoves is expected to have a sustainable positive impact in the partner notification practice among youth and contribute to increasing the awareness of STI prevention

Validation of the Spanish Version of the Minnesota Living With Heart Failure Questionnaire ORIGINAL ARTICLES Validación de la versión española del Minnesota Living with Heart Failure Questionnaire

Introduction and objectives. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most commonly used instrument for evaluating quality of life in patients with heart failure. It comprises 21 items and 2 dimensions: the physical and the emotional. The aim of this study was to assess the psychometric properties of the Spanish version of the MLHFQ. Methods. The MLHFQ and the 36-item short form (SF-36) questionnaire were administered 1 and 2 months after discharge to 677 patients who had been hospitalized for heart failure. Patients were classified as either stable (n=245) or unstable (n=103) on the basis of New York Heart Association (NYHA) functional class and 3 other functional capacity variables. Reliability was evaluated using measures of internal consistency (Cronbach&apos;s alpha) and reproducibility (the intraclass correlation coefficient [ICC]). Validity was assessed by looking at the scores by NYHA class, and at correlations between scores on MLHFQ and SF-36 dimensions. Responsiveness to change was evaluated using the effect size. Results. Cronbach&apos;s alpha was ≥0.8 for the 3 MLHFQ scores, and the ICC was also large (0.74-0.83). In addition, MLHFQ scores varied significantly with functional class (P&lt;.001), and there were intermediate-tohigh correlations with the assumed corresponding SF-36 dimensions (0.74-0.52). The observed effect sizes were small or intermediate (0.09-0.44). Conclusions. The Spanish version of the MLHFQ demonstrated adequate metric properties, comparable to the original. These results support the use of the MLHFQ in Spanish heart failure patients, although it would be advisable to re-evaluate its responsiveness to change. Validación de la versión española del Minnesota Living with Heart Failure Questionnaire Introducción y objetivos. El Minnesota Living with Heart Failure Questionnaire (MLHFQ) es el instrumento más utilizado para la evaluación de la calidad de vida en pacientes con insuficiencia cardiaca. Contiene 21 ítems y dos dimensiones: física y emocional. El objetivo de este estudio es evaluar las propiedades métricas de la versión española del MLHFQ. Métodos. Se aplicó, 1 y 2 meses después del alta, el MLHFQ y el SF-36 a 677 pacientes ingresados por insuficiencia cardiaca. A partir de la clasificación NYHA y otras 3 variables de capacidad funcional, se definió a los pacientes como estables (n = 245) o con cambio (n = 103). De la fiabilidad, se estudió: la consistencia interna (alfa de Cronbach) y la reproducibilidad (coeficiente de correlación intraclase [CCI]). La validez se estudió con las puntuaciones según la clase funcional y las correlaciones con las dimensiones del SF-36. La sensibilidad al cambio se evaluó por el tamaño del efecto. Resultados. El alfa de Cronbach fue ≥ 0,8 en las tres puntuaciones, y el CCI también fue elevado (0,83). Las puntuaciones del MLHFQ mostraron diferencias según la clase funcional (p &lt; 0,001), así como correlaciones moderadas-altas con las dimensiones del SF-36 planteadas a priori (0,74-0,52). Los cambios observados fueron pequeños o moderados (0,44). Conclusiones. La versión española del MLHFQ ha mostrado unas adecuadas propiedades métricas, igual que la original. Estos resultados respaldan el uso del MLHFQ en pacientes españoles con insuficiencia cardiaca, aunque sería recomendable reevaluar su sensibilidad al cambio

Shoulder strength changes one year after axillary lymph node dissection or sentinel lymph node biopsy in patients with breast cancer

OBJECTIVES: To assess the changes in shoulder strength of patients with breast cancer during the first year after surgery; and to compare the effect of sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) on shoulder strength. DESIGN: Prospective longitudinal observational study from presurgery to 1 year after. SETTING: Tertiary hospital. PARTICIPANTS: Of 129 consecutive patients examined for eligibility, a sample of women (N=112) with breast cancer were included (44 underwent ALND, and 68 underwent SLNB). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Difference between the affected and unaffected arm in strength of shoulder external rotators, internal rotators, abductors, and serratus anterior, measured by dynamometry. Evaluations were performed prior to surgery and at 1, 6, and 12 months after surgery. RESULTS: After breast cancer ALND surgery, strength decreased significantly at the first month for internal rotators, without having recovered presurgery values after 1 year of follow-up, with a mean difference of 2.26kg (P=.011). There was no significant loss of strength for patients treated with SLNB. The loss of shoulder range of motion was only significant the first month for the ALND group. The factors identified as associated with strength loss in the general estimating equation models were the ALND surgery and having received physical/occupational therapy during follow-up. CONCLUSIONS: One year after breast cancer surgery, patients treated with ALND had not recovered their previous shoulder internal rotators strength, whereas those who underwent SLNB presented no significant loss of strength. This provides important information for designing rehabilitation programs targeted specifically at the affected muscle group after nodal surgical approach.This study was sponsored by a government grant from: Instituto de Salud Carlos III FEDER (PI06/90070