Overcoming barriers to opioid-induced constipation management in cancer patients.

PURPOSE: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. We aim to identify the main barriers hindering clinical recommendations implementation and propose consensus solutions to improve OIC control in cancer patients. METHODS: Following collaborative and prioritization techniques, a scientific committee generated statements addressing possible barriers to optimal OIC management (related to patients, health providers and health care system), and potential interventions to overcome these barriers. An expert panel of 36 oncologists assessed the statements to reach a consensus. RESULTS: The survey consisted of 70 statements. Consensus was reached on 12/45 items related to barriers (26.6%) and on 19/25 items about corrective interventions (76%). The panel considered that patients are unaware of the existence of a specific OIC treatment, and their information sources are highly variable and unreliable. Regarding health providers, the panel considered that the oncologists prioritize symptoms such as diarrhea, pain, anxiety, or other treatment toxicities, over constipation. Work overload and bureaucratic requirements were the main barriers related to health care system. Regarding potential interventions, best-rated proposals included specific training programs development for primary care physicians and nurses, and multiplatform informative resources development for patients and caregivers, including precisely written instructions about OIC recognition and management. Oncologists assessed positively measures aiming to improve coordination between primary care physicians and oncologists, and nursing consultations implementation. The panel considered useful the OIC treatment algorithms simplification. CONCLUSIONS: The expert panel identified the main barriers to optimal OIC management and suggested some feasible approaches to overcome these barriers.

PD-L1 testing and clinical management of newly diagnosed metastatic non-small cell lung cancer in Spain: MOREL study.

AIM: To describe the clinical management and PD-L1 testing of patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC) without driver mutations in Spain. METHODS: Multicenter, retrospective study. RESULTS: Among 297 evaluated patients, 89.2% received systemic treatment for stage IV disease, of whom 53.6% received platinum doublet therapy, 26.8% immunotherapy as monotherapy and 14.7% immunotherapy + chemotherapy, with 9.4% receiving treatment as part of a clinical trial. Treatment was initiated 1 month after histological diagnosis, with PD-L1 test results available in most cases (92.6%). PD-L1 testing was performed in 287 patients, 95.1% by in-house tests, mostly with the 22C3 pharmDx assay. The factor most strongly associated with treatment selection was, as expected, the expression of PD-L1. CONCLUSION: PD-L1 testing is implemented in clinical practice and seems to guide treatment decisions in patients with NSCLC in Spain.

Exploring Potential Benefits of Accumulated Multicomponent-Training in Non-Active Older Adults: From Physical Fitness to Mental Health.

The present study aimed to analyze the impact of a multicomponent training (MCT) program in a group of non-active older adults, comparing two different dose distributions. Twenty-four individuals, assigned to two groups, completed 15 weeks of MCT (2 days/week). The continuous group (CMCT; n = 14, 9 females; 71.07 ± 5.09 years) trained for 60 min/session in the morning. The accumulated group (AMCT; n = 10, 5 females; 72.70 ± 3.59 years) performed the same exercises, volume, and intensity, but the training was distributed twice per day (30 min in the morning; 30 more in the afternoon). Bonferroni post hoc comparisons revealed significant (p < 0.001) and similar large improvements in both groups in lower limb strength (five times sit-to-stand test: CMCT, 12.55 ± 2.83 vs. 9.44 ± 1.72 s; AMCT, 10.37 ± 2.35 vs. 7.46 ± 1.75 s). In addition, there were large gains in preferred walking speed and instrumental daily life activities, which were higher for CMCT and AMCT, respectively (in this order: 1.00 ± 0.18 vs. 1.44 ± 0.26 m/s and 1.09 ± 0.80 vs. 1.58 ± 0.18 m/s; 33.07 ± 2.88 vs. 36.57 ± 1.65 points and 32.80 ± 1.93 vs. 36.80 ± 0.92 points); improvements in cardiorespiratory fitness, now moderate for CMCT (474.14 ± 93.60 vs. 529.64 ± 82.76 m) and large for AMCT (515.10 ± 20.24 vs. 589.60 ± 40.38 m); and medium and similar enhancements in agility in both groups (TUG test: CMCT: 7.49 ± 1.11 vs. 6.77 ± 1.16 s; AMCT: 6.84 ± 1.01 vs. 6.18 ± 0.62 s). None of the protocols had an impact on the executive function, whereas health-related quality of life showed a trend to significance in the whole sample only (EQindex overall sample, p = 0.062; d = 0.48 CMCT; d = 0.34 AMCT). Regardless of the type of dose distribution, starting multicomponent training improves physical function in non-active older adults, but does not improve cognitive function at mid-term. Because both forms of MCT showed similar compliance, slightly positive differences in accumulated strategies may indicate some benefits related to breaking afternoon sedentary behaviors, which deserves further research in longer and larger interventions. The mixed nature of MCT suggests accumulative group interventions may be a promising approach to address sedentary aging.

Inspiratory Muscle Strength and Cardiorespiratory Fitness Association With Health-Related Quality of Life in Healthy Older Adults.

The main purpose of this study was to explore similarities and differences in the association between two capabilities affecting the cardiorespiratory system (overall and multifactorial cardiorespiratory fitness and inspiratory muscle strength) and the health-related quality of life (HRQoL), in a group of active healthy seniors. Sixty-five individuals (age, 73.01 ± 5.27 years; 53 women) who participated regularly in a multicomponent training program completed the EuroQol 5D-5L questionnaire, the 6-min walking test (6MWT), and the maximum inspiratory pressure test (MIP). Non-parametric correlations (Spearman's rho) were conducted to analyze the association between HRQoL indices (EQindex and EQvas), MIP, and 6MWT, considering both, the whole sample and men and women separately. Furthermore, partial correlation was made by controlling age and sex. We found a moderate association between HRQoL and cardiorespiratory fitness (EQvas: r = 0.324, p = 0.009; EQindex: r = 0.312, p = 0.011). Considering sex, relationship EQvas-6MWT decrease to small (r = 0.275; p = 0.028) whereas EQindex-6MWT remained moderated (r = 0.425; p = 0.000). When we considered women and men separately, the association between HRQoL and 6MWT appeared only in women, while the observed strong trend (p = 0.051) toward a large and positive association between EQindex and MIP, mediated by the covariate age, appeared only in men. Conversely to the cardiorespiratory fitness, MIP is not a limiting factor of HRQoL in healthy active elderly. Moreover, MIP and HRQoL should be included in the assessment of exercise interventions because they provide different information about the cardiorespiratory system deterioration. Similarly, EQvas and EQindex confirm to be complementary in the assessment of HRQoL. Furthermore, like aging process is different for men and women, the association between MIP and cardiorespiratory fitness with HRQoL may behave differently, so keeping on research these associations could help to improve training programs for this population.

120 min/week of neuromotor multicomponent training are enough to improve executive function and functional fitness in older women.

PURPOSE: The study aimed at comparing the effects of a neuromotor multicomponent training program (MCTP) on executive function, functional fitness, blood pressure, body composition and health-related quality of life (HRQOL), compared with a concurrent strength and endurance exercise training program (CONTROL-EXE) and a cognitive training program (CONTROL-COG). METHODS: 56 older women (73 ± 6 years) completed the 30-weeks intervention. The three groups attended two 60-min sessions per week and they were assessed before and after the intervention. RESULTS: MCTP showed a moderate improvement in Stroop C condition (28 ± 7 vs 32 ± 8 correct items; p = 0.001; d = 0.53) and Stroop interference score (-7.4 ± 7.3 vs -3.7 ± 6.1; p = 0.035; d = 0.55), while no changes were observed among control groups. MCTP showed a small to moderate improvement in Timed Up and Go test (TUGT) (5.85 ± 0.58 vs 5.46 ± 0.56 s; p < 0.001; d = 0.71) and Chair-Stand test (CST) (18 ± 4 vs 19 ± 4 repetitions; p < 0.001; d = 0.47); while CONTROL-EXE only improved moderately at TUGT (7.02 ± 1.1 vs 6.44 ± 0.91 s; p = 0.005; d = 0.59) and CONTROL-COG showed a moderate to small worsening in TUGT, CST and handgrip strength. Additionally, MCTP enhanced body composition and HRQOL. Lastly, both exercise groups showed lowered blood pressure values. CONCLUSIONS: Our results suggest that a neuromotor MCTP could be considered as a highly suitable training to enhance executive function, functional fitness, HRQOL and body composition in older women.

Multicomponent Exercise Training Combined with Nutritional Counselling Improves Physical Function, Biochemical and Anthropometric Profiles in Obese Children: A Pilot Study.

Aerobics or strength exercise plus diet interventions have been shown to counteract childhood obesity. However, little is known with regard to periodized multicomponent exercise interventions combined with nutritional counselling, which might be less demanding but more enjoyable and respectful of children and adolescents' nature. In order to analyze the impact of such a multimodal approach, 18 obese children (10.8 ± 1.6 years; 63% females; z Body Mass Index 3 ± 0.4) trained for 60 min, twice weekly and were measured for body composition, biochemical parameters and physical function. We found that 16 weeks of multimodal intervention (14 of training), based on fun-type skill-learning physical activities and physical conditioning with challenging circuits and games, together with nutritional counselling, led to an attendance > 80%, with significant overall health improvement. Body composition was enhanced (p < 0.01 for z BMI, mid-upper-arm-circumference, waist-to-height ratio, tricipital and subscapular skinfolds, body-fat % by Slaughter equation and Dual energy X-ray absorptiometry body fat% and trunk fat%), as well as metabolic profile (LDL cholesterol, gamma-glutamyl transferase , alanine aminotransferase ; p < 0.05), homeostatic model assessment of insulin resistance (HOMA-IR; p < 0.05) and inflammatory response (C-Reactive Protein; p < 0.05). Physical fitness was also improved (p < 0.01) through better cardiovascular test scores and fundamental movement patterns (Functional Movement Screen-7, FMS-4). Tailoring multimodal supervised strategies ensured attendance, active participation and enjoyment, compensating for the lack of strict caloric restrictions and the low volume and training frequency compared to the exercise prescription guidelines for obesity. Nutritional counselling reinforced exercise benefits and turned the intervention into a powerful educational strategy. Teamwork and professionals' specificity may also be key factors.

Short and Long-Term Trainability in Older Adults: Training and Detraining Following Two Years of Multicomponent Cognitive-Physical Exercise Training.

Despite the benefits of multicomponent physical-cognitive training programs (MCCogTPs), lower training intensities in the concurrent approach, and bigger heterogeneity with aging, suggest the need for long-term analyses, with special attention to training and detraining in older adults. The present study aims to examine these training/detraining effects in a two year MCCogTP, looking for specific dynamics in the trainability of their physical and cognitive capacities. The intervention was divided into four periods: T1, T2 (8 months of training each), and D1, D2 (3.5 months of detraining plus 0.5 of testing each). Twenty-five healthy seniors (70.82 ± 5.18 years) comprised the final sample and were assessed for cardiovascular fitness (6-minutes walking test), lower-limbs strength (30-seconds chair-stand test) and agility (8-feet timed up-and-go test). Inhibition (Stroop test) was considered for executive function. Physical and cognitive status improved significantly (p < 0.05) throughout the two years, with larger enhancements for physical function (mainly strength and agility). Strength and cardiovascular fitness were more sensitive to detraining, whilst agility proved to have larger training retentions. Inhibition followed an initial similar trend, but it was the only variable to improve along D2 (d = 0.52), and changes were not significant within periods. Notwithstanding aging, and the exercise cessation in D2, physical and cognitive status remained enhanced two years later compared to baseline, except for lower-limb strength. According to these results, basic physical capacities are very sensitive to training/detraining, deserving continuous attention (especially strength). Both reducing detraining periods and complementary resistance training should be considered. Additionally, physical enhancements following MCcogTPs may help cognition maintenance during detraining.

Continuous Compared to Accumulated Walking-Training on Physical Function and Health-Related Quality of Life in Sedentary Older Persons.

The present study aimed to analyze the impact of overground walking interval training (WIT) in a group of sedentary older adults, comparing two different dose-distributions. In this quasi-experimental and longitudinal study, we recruited twenty-three sedentary older adults (71.00 ± 4.10 years) who were assigned to two groups of WIT. The continuous group (CWIT) trained for 60 min/session in the morning, while the accumulated group (AWIT) performed the same duration and intensity of exercise, but it was distributed twice a day (30 min in the morning and 30 more in the afternoon). After 15 weeks of an equal external-load training (3 days/week), Bonferroni post-hoc comparisons revealed significant (p < 0.050) and similar large improvements in both groups in cardiorespiratory fitness and lower limb strength; even larger gains in preferred walking speed and instrumental daily life activity, which was slightly superior for CWIT; and improvements in agility, which were moderate for CWIT and large for AWIT. However, none of the training protocols had an impact on the executive function in the individuals, and only the AWIT group improved health-related quality of life. Although both training protocols induced a general significant improvement in physical function in older adults, our results showed that the accumulative strategy should be recommended when health-related quality of life is the main target, and the continuous strategy should be recommended when weakness may be a threat in the short or medium term.

Strategies to change body composition in older adults: do type of exercise and dose distribution matter?

BACKGROUND: This study aims to analyze changes in sedentary elderlies' body composition, comparing the impact of two dose distributions: continuous (60 min/session) vs. accumulated (30 min/session in the morning and 30 min/session in the afternoon), on two types of physical exercise programs (multicomponent-training [MCT] vs. walking interval-training [WIT]). METHODS: Forty-six sedentary overweight elderly (71.3±4.3 years) were evaluated by bioimpedance with a pre-post 2x2 factorial design. Participants were distributed in four homogeneous groups, considering gait and health parameters. RESULTS: The overall sample showed significant improvements in fat mass (% and kg) and fat-free mass (kg) following 15 weeks of training. There was a main effect of "type of exercise" and a moderating effect of "dose distribution" reflected in the interaction of both factors. Bonferroni analyses of the type*dose interaction revealed significant improvements in all groups, except for MCT-accumulated, on both body composition compartments. CONCLUSIONS: Starting exercise training, properly periodized and supervised by physical-education trainers, improves body composition of sedentary elderlies regardless of the type of exercise. Accumulated strategies were beneficial only when applied to WIT. Although MCT training improves body composition with only 2 days/week, WIT-accumulated could be a key element in the design of weight control policies looking for breaking sedentary behaviors.

Mujer de 68 años con síndrome de ojos bailarines / A-68-year-old woman with dancing eyes syndrome

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Beneficial Effects of Inspiratory Muscle Training Combined With Multicomponent Training in Elderly Active Women.

Purpose: This study aims to analyze changes in Maximum Inspiratory Pressure (MIP), lung function, cardiorespiratory fitness, and blood pressure, in 10 healthy active elderly women, following 7 weeks of inspiratory muscle training (IMT) combined with a multicomponent training program (MCTP). The association among these health parameters, their changes after training (deltas), and the influence of MIP at baseline (MIPpre) are also considered. Methods: IMT involved 30 inspirations at 50% of the MIP, twice daily, 7 days a week, while MCTP was 1 hr, twice a week. MIP, lung function (FVC, FEV1, FEV1/FVC, FEF25-75%, PEF), 6MWT, and blood pressure (SBP, DBP), jointly with body composition, were assessed before and after the intervention. Results: Seven weeks were enough to improved MIP (p = .019; d = 1.397), 6MWT (p = .012; d = .832), SBP (p = .003; d = 1.035) and DBP (p = .024; d = .848). Despite the high physical fitness (VO2 peak: M = 23.38, SD = 3.39 ml·min·Kg-1), MIPpre was low (M = 39.00, SD = 7.63 cmH2O) and displayed a significant negative correlation with ΔMIPpre-post (r = -.821; p < .004), showing that women who started the intervention with lower MIP achieved higher improvements in inspiratory muscle strength after training. Conclusions: No significant changes in spirometric parameters may signal that lung function is independent of early improvements in inspiratory muscles and cardiorespiratory fitness. Absence of correlation between physical fitness and respiratory outcomes suggests that being fit does not ensure cardiorespiratory health in active elderly women, so IMT might be beneficial and should supplement the MCTP in this population.

[Euthanasia in patients with cancer and the continuous-care providers]. / La eutanasia en el paciente con cáncer y los cuidados continuos.

During the clinical evolution of patients with cancer there are many occasions, or phases of the disease, when there are no specific treatments and, as such, we need to provide maximum comfort following appropriate symptom control; in this stage it is fundamental to respect personal autonomy together with the option to reject futile treatment. With appropriate control of symptoms it is possible to reach the stage where the majority of the patients do not continue to suffer. Continuous-care providers for cancer patients are those who are responsible for providing help to resolve these situations. In palliative medicine there are highly-efficacious procedures to the help in these last hours. Sedation is applied when it is impossible to control symptoms by other means. With appropriate Carer cover, it is not necessary to introduce laws on assisted suicide and/or active voluntary euthanasia, neither because of the magnitude of demand, nor because of the difficulties in achieving appropriate control of symptoms.

La eutanasia en el paciente con cáncer y los cuidados continuos / Euthanasia in patients with cancer and the continuous-care providers

La evolución de los enfermos con cáncer conduce en muchas ocasiones a fases de la enfermedad en las que no existen tratamientos específicos y éstos debemos aplicarlos en la consecución del máximo confort a través de un adecuado control sintomático, en esa etapa es fundamental el respeto de la autonomía personal y la posibilidad del rechazo de tratamientos fútiles. Con el adecuado control de síntomas es posible lograr que la mayoría de los enfermos no padezcan sufrimientos. Los cuidados continuos en el paciente oncológico son los responsables de ayudarnos a resolver estas situaciones. En medicina paliativa existe un procedimiento altamente eficaz en la ayuda en las últimas horas, la sedación, aplicable cuando sea imposible el control sintomático con otros medios. Con una cobertura adecuada de cuidados no debería ser necesario introducir leyes de suicidio asistido y/o eutanasia activa voluntaria, ni por la magnitud de la demanda, ni por las dificultades en el adecuado control sintomático

During the clinical evolution of patients with cancer there are many occasions, or phases of the disease, when there are no specific treatments and, as such, we need to provide maximum comfort following appropriate symptom control; in this stage it is fundamental to respect personal autonomy together with the option to reject futile treatment. With appropriate control of symptoms it is possible to reach the stage where the majority of the patients do not continue to suffer. Continuous-care providers for cancer patients are those who are responsible for providing help to resolve these situations. In palliative medicine there are highly-efficacious procedures to the help in these last hours. Sedation is applied when it is impossible to control symptoms by other means. With appropriate Carer cover, it is not necessary to introduce laws on assisted suicide and/or active voluntary euthanasia, neither because of the magnitude of demand, nor because of the difficulties in achieving appropriate control of symptoms

[Analysis of tumour-derived DNA in serum in advanced non-microcytic lung cancer: might it be a prognostic factor?]. / Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: 'es útil como factor pronóstico?

INTRODUCTION: Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. OBJECTIVE: To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. METHODS: Serum DNA from 78 patients was purified and spectrophotometrically quantified. RESULTS: No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] < 500 ng/ml TTP = 7.25 months, 95%CI: 3.5-5.25; [DNA ] > or = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). CONCLUSIONS: Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease.

Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: ¿es útil como factor pronóstico? / Analysis of tumour-derived DNA in serum in advanced non-microcytic lung cancer: might it be a prognostic factor?

Introducción. El ADN sérico de pacientes oncológicos puede permitir detectar alteraciones genéticas específicas del tumor. Objetivo. Estudiar la concentración de ADN sérico ([ADN]) en pacientes con cáncer de pulmón no microcítico (CPNM) avanzado. Evaluar su relación con la edad, histología, estadio, respuesta, tiempo a la progresión (TTP) y supervivencia. Métodos. Se purificó el ADN sérico de 78 pacientes y se cuantificó espectrofotométricamente. Resultados. No hubo diferencias significativas entre [ADN] media y edad, histología, respuesta, y supervivencia. Hubo significatividad respecto al estadio (IIIB= 408,75 ng/ml; IV= 478,74 ng/ml; p= 0,02). Agrupando los pacientes según el [ADN] hubo significatividad en TTP estableciendo un punto de corte en 500 ng/ml ([ADN] = 500 ng/ml, TTP=4,25 meses, IC 95% 2-6,5; p= 0,05). Conclusiones. La cuantificación del ADN sérico resulta sencilla mediante este método, pero presenta deficiencias debido a la variabilidad intermuestral y a la baja especificidad, al medirse el [ADN] total sin especificar su asociación o no al tumor. Nuestro estudio sugiere que el [ADN] está relacionado con el pronóstico permitiendo un análisis evolutivo

Introduction. Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. Objective. To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. Methods. Serum DNA from 78 patients was purified and spectrophotometrically quantified. Results. No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). Conclusions. Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease