Translational value of preclinical models for renal denervation: a histological comparison of human versus porcine renal nerve anatomy.

BACKGROUND: Preclinical models have provided key insights into the response of local tissues to radiofrequency (RF) renal denervation (RDN) that is unobtainable from human studies. However, the anatomic translatability of these models to the procedure in humans is incompletely understood.  Aims: We aimed to compare the renal arterial anatomy in normotensive pigs treated with RF-RDN to that of human cadavers to evaluate the suitability of normotensive pigs for determining the safety of RF-RDN. METHODS: Histopathologic analyses were performed on RF-treated renal arteries in a porcine model and untreated control renal arteries. Similar analyses were performed on untreated renal arteries from human cadavers.  Results: In both human and porcine renal arteries, the median number of nerves was lower in the more distal sections (the numbers in the proximal, middle, distal, 1st bifurcation, and 2nd bifurcation sections were 65, 58, 47, 22.5, and 14.7 in humans, respectively, and 39, 26, 29, 16.5, and 9.3 in the porcine models, respectively). Renal nerves were common in the regions between arteries and adjacent veins, but only 3% and 13% of the renal nerves in humans and pigs, respectively, were located behind the renal vein. The semiquantitative score of RF-induced renal arterial nerve necrosis was significantly greater at 7 days than 28 days (0.98 vs 0.75; p=0.01), and injury to surrounding organs was rarely observed. CONCLUSIONS: The distribution of nerve tissue and the relative distribution of extravascular anatomic structures along the renal artery was similar between humans and pigs, which validates the translational value of the normotensive porcine model for RDN.

Histological evidence supporting the durability of successful radiofrequency renal denervation in a normotensive porcine model.

BACKGROUND: Sustained blood pressure reductions after radiofrequency (RF) renal denervation (RDN) have been reported to 3 years in patients with uncontrolled hypertension. However, mechanistic data to support procedural durability are lacking. We aimed to quantify the long-term nerve anatomic and functional effects of RF RDN in a preclinical model. METHODS: Bilateral RF RDN was performed in 20 normotensive swine. Renal tissue samples were obtained in the RDN-treated groups at 7 ( n  = 6), 28 ( n  = 6), and 180 days ( n  = 8) postprocedure for quantification of cortical norepinephrine (NE) levels and renal cortical axon density. Tissue fibrosis, necrosis and downstream nerve fiber atrophy (axonal loss) were also scored for each sample. Three additional untreated groups ( n  = 6, n  = 6 and n  = 8, respectively) served as control. RESULTS: Pathologic nerve changes were characterized by necrosis in the ablated region at 7 days that partially resolved by 28 days and fully resolved at 180 days. Axonal loss was apparent within and downstream to the ablation regions and was evident at 7, 28 and 180 days in the main vessel and branch vessels. Consequently, renal cortical axon density and corresponding cortical NE levels were significantly reduced at 7 days in the RDN vs. control group and remained suppressed at 180 days. CONCLUSIONS: Reductions in renal NE, cortical axon density and downstream axonal loss caused by axonal destruction persisted through 180 days post-RDN in a normotensive swine model. These results suggest functional nerve regrowth after RF RDN is unlikely and support published clinical evidence that the procedure results in durable blood pressure reduction.

Time, Temperature, Power, and Impedance Considerations for Radiofrequency Catheter Renal Denervation.

Radio frequency (RF) based percutaneous catheter renal denervation systems offer an additional clinical tool, along with lifestyle modification and drug therapy, to address the global epidemic of uncontrolled hypertension. The most widely applied RF system has been designed to optimize both procedural and safety and efficacy. Lesion size, shape, and depth result from a complex interaction of device design, anatomy, and tissue electrical conduction properties. Power control algorithms must be carefully designed, incorporating feedback to maximize nerve destruction while minimizing collateral damage. Physical and numerical modelling as well as analysis of sensor feedback provide insight into design performance that cannot be derived from clinical trials. This review is focused on key design and performance aspects of the most widely applied renal denervation system meant to optimize safety and efficacy of the procedure.

Does it matter how we evaluate HRQOL? Longitudinal comparison of the EORTC QLQ-C30/QLQ-OG25 and FACT-E.

PURPOSE: To determine whether EORTC QLQ-C30/QLQ-OG25 and FACT-E compared longitudinally provide similar reflections of health-related quality of life (HRQOL). METHODS: Eighty-six esophageal cancer patients treated with curative intent, scheduled to complete both questionnaires at baseline and post-treatment time points until 36 months. A generalized estimating equation model utilizing a Gaussian family compared instruments longitudinally. The two-one-sided-test (TOST) method assessed equivalence between the instruments. RESULTS: Trajectories for social domain and overall quality of life differed significantly between instruments. Also, FACT-G's functional well-being post-treatment returns to baseline 3-6 months earlier than the EORTC QLQ-C30's role functioning subscale, suggesting measurement of different components. Trajectories for physical and esophageal symptom subscales are similar and are deemed equivalent. Emotional domains are comparable and bear little resemblance to the physical domain trajectories indicating reflection of emotional experience rather than a physical proxy. EORTC QLQ-C30 subscales have a trajectory similar to its physical functioning scale except for the emotional and esophageal symptoms scales. Overall HRQOL in both instruments showed a consistent return to baseline/pre-treatment levels by 6 months post-treatment. CONCLUSIONS: Overall HRQOL recovers earlier after curative-intent treatment than previously reported despite persistence of physical symptoms, with a consistent return to pre-treatment levels by 6 months after treatment. This supports the concept that HRQOL is not primarily defined by physical function. Based on this longitudinal comparison, FACT-E provides a more multidimensional assessment of HRQOL. IMPLICATIONS FOR CANCER SURVIVORS: Curative intent treatment for esophageal cancer has adverse effects on HRQOL but despite intense treatment, overall HRQOL recovers within 6 months.

Longitudinal Evaluation of Trial Outcome Index Scores in Patients With Esophageal Cancer.

BACKGROUND: The purpose of this study was to use the Trial Outcome Index (TOI) to longitudinally assess the effects of treatment for esophageal cancer. METHODS: Patients with esophageal cancer treated with curative intent therapy (N = 84) were evaluated with Functional Assessment of Cancer Therapy-Esophageal Cancer subscale (FACT-E) questionnaires, which were scheduled at baseline and at 1, 3, 6, 9, 12, 18, 24, and 36 months after completion of treatment. Patients treated with preoperative therapy also completed questionnaires 6 to 8 weeks after starting treatment and after completion of induction treatment (12-14 weeks) just before the operative procedure. Physical and functional well-being subscales and the esophageal specific concerns that comprise the TOI were used for the analysis. A linear mixed-effects model with identity link function was used for longitudinal TOI scores. Tukey-Kramer adjustment for multiple comparisons was used for pairwise comparisons. RESULTS: TOI scores differed over time (p < 0.0001), with a significant decrease in TOI from baseline to 6 to 8 weeks after chemotherapy or chemoradiation (p < 0.0001; median, 95 versus 68). At 1 month after treatment (esophagectomy or definitive chemoradiation), median TOI scores were 79 (p = 0.0011 compared with baseline). However by 3 months after treatment, median scores were 90, not significantly different from baseline (p = 0.23). Beyond 3 months, TOI scores either increased or stabilized. Single patients have TOI scores 12 points lower than patients with partners (p = 0.0015). CONCLUSIONS: TOI is a useful tool to assess the physical and functional effects of treatment in patients with esophageal cancer and may provide an efficient index for the comparison of different types of treatment, particularly in the context of clinical trials.

Impact of a pedometer program on nurses working in a health-promoting hospital.

The aim of this research was to describe the impact of a pedometer-based activity program on a subset of nurses in a university-affiliated, multisite health care center in Canada. This study used a longitudinal design with preintervention-postintervention (8 weeks) and follow-up (6 months). At baseline, 60 nurses participated; 51 (85%) remained for the postprogram assessment and 33 (55%) also completed the follow-up questionnaire. Data were collected through self-administered questionnaires (weight, height, fatigue, insomnia, stress and step data) and blood tests (total cholesterol and low-density lipoprotein and high-density lipoprotein cholesterol). At postprogram, participants reported 12 thinsp;912 steps on average per day. At follow-up, 79% of participants indicated that they maintained their physical activity after the pedometer program. A significant decrease in insomnia was evident in postprogram scores compared with baseline scores, and this decrease was maintained at follow-up. A significant decrease in minutes spent sitting per week was also observed from baseline to postprogram and also maintained at follow-up. Participants' stress and low-density lipoprotein cholesterol levels decreased from baseline to postprogram (marginally significant). Finally, their weight decreased from baseline to follow-up (marginally significant). The pedometer program generated some positive outcomes for nurses after 6 months.

Determinants and benefits of physical activity maintenance in hospital employees.

This study investigated whether the positive behavioral and anthropometric outcomes of a pedometer-based physical activity 8-week challenge were maintained 6 months after the end of the program. It further investigated the motivational profile of those who maintained their physical activity levels in the months following the end of the program and of those who did not. Hospital employees from a university-affiliated multisite health care center in Canada participated using a questionnaire. Of the 235 participants who completed the 8-week challenge, 157 questionnaires were returned 6 months later. Paired-samples t tests were conducted between the baseline and follow-up scores as well as between the postprogram and follow-up scores to detect significant differences between the measurement points. This study shows that the pedometer-based physical activity helped hospital employees maintain a high level of physical activity as well as maintain a healthy body mass index after 6 months. The results demonstrated that during maintenance the high physical activity group obtained higher scores for identified regulation and intrinsic regulation compared with the other groups. The results of the study revealed that identified and intrinsic regulations are important contributors to maintaining physical activity among hospital employees.

Perceived communication between physicians and breast cancer patients as a predicting factor of patients' health-related quality of life: a longitudinal analysis.

OBJECTIVE: Communication between cancer patients and healthcare providers is recognized as an important aspect of these patients' health-related quality of life (HRQOL). Nevertheless, no study has examined whether perceived communication between physicians and breast cancer patients is a determining factor in their HRQOL along the disease's trajectory. This longitudinal study aimed to ascertain whether such communication influenced the HRQOL of such women at three points in time. METHODS: The sample consisted of 120 French-speaking women with stage I or II breast cancer aged 18 years or over (mean = 55 years) who underwent a lumpectomy with adjuvant treatment. The women filled out questionnaires at three different times: around the time of diagnosis, halfway through radiotherapy and at follow-up. Either at the hospital or at home, they completed demographic and medical data questionnaires, the Medical Outcomes Study-Social Support Survey, an HRQOL questionnaire (EORTC QLQ-C30/BR23) and the Medical Communication Competence Scale. RESULTS: Generalized estimated equations analyses indicated that the women's perceptions of their own communication skills towards physicians had a greater impact on their HRQOL than the women's perception of physicians' communication skills. The women had better global health and better role, emotional, cognitive and sexual functioning as well as fewer side effects and symptoms during radiotherapy and at follow-up when they perceived themselves as competent communicators at diagnosis and during radiotherapy. CONCLUSIONS: The results underscore the importance for breast cancer patients of being proactive in information seeking and in the socio-emotional aspect of their relationship with physicians to enhance their HRQOL.

Implementation of diagnosis-related mental health programs: impact on health care providers.

Mental health services are in the midst of change in different countries. In Quebec (Canada), the government has adopted a Mental Health Action Plan (2005-2010). In this context, 2 psychiatric institutions have developed and implemented a mental health services organization model based on diagnosis-related mental health programs and support for frontline services. This article presents the impact on health care providers of implementation of diagnosis-related mental health programs in the context of transformation of mental health services.