Managing cancer‐related fatigue in men with prostate cancer: A systematic review of non‐pharmacological interventions

The aim of this systematic review was to synthesize the best available evidence informing the effectiveness of non‐pharmacological interventions for managing cancer‐related fatigue in men treated for prostate cancer. This review considered experimental studies that included men with prostate cancer (regardless of staging, previous treatment or comorbidities), aged 18 years and over who were undergoing any treatment, or had completed any treatment for prostate cancer within the previous 12 months. Three interventions were identified for the management of cancer‐related fatigue in men with prostate cancer. Evidence from five studies including 447 participants demonstrates the effectiveness of physical activity, both aerobic and resistance exercise, and from three studies including 153 participants suggesting the benefits of psychosocial interventions including education and cognitive behavioural therapy. Health professionals require knowledge of a range of effective interventions aimed at reducing cancer‐related fatigue in men with prostate cancer and should incorporate those interventions into their patient management. Although physical activity appears to show the greatest benefit, other non‐pharmacological interventions such as education and cognitive behavioural therapy have demonstrated benefit and should also be considered as a strategy in treating this debilitating side effect of cancer and its treatment.     

Tiotropium Respimat Soft Mist Inhaler versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD

Purpose

Patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality as a result of various alterations in oxygenation parameters and sleep macro- and micro-architecture. There is a shortage of data to support the efficacy of long-acting inhaled anticholinergic agents in improving these adverse effects, which are known to have a negative impact on clinical outcomes. We aimed to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO₂) and sleep quality in patients with COPD.

Methods

In a randomized, open-label, parallel-group trial involving 200 patients with mild to moderate COPD (resting arterial oxygen tension >60 mmHg while awake), we compared the effects of 6 months’ treatment with the two devices on sleeping SaO₂ and sleep quality. Overnight polysomnography and pulmonary function testing were performed at baseline and after 6 months’ treatment.

Results

A total of 188 patients completed the trial. Both groups showed significant improvement in minimum sleep SaO₂ and time of sleep spent with SaO₂ below 90 (TST90) compared to baseline. The patients using the Respimat had significantly better TST90 than did those using the HandiHaler. Sleep disturbance was highly variable in these patients, but the sleep stage durations were significantly better in the Respimat group.

Conclusions

Sleeping SaO₂ can be improved by tiotropium delivered using either the HandiHaler device or the Respimat Soft Mist Inhaler. However, the patients who used the Respimat device had significantly better TST90 and sleep architecture parameters.

     

Recombinant methionyl human leptin administration to achieve high physiologic or pharmacologic leptin levels does not alter circulating inflammatory marker levels in humans with leptin sufficiency or excess

A role for high leptin levels in the proinflammatory state associated with obesity has been proposed on the basis of observational studies, but a recent interventional study employing administration of long-acting pegylated leptin resulting in very high pharmacologic levels in obese subjects did not support this idea. These interventional studies have not yet been independently confirmed, however, and varying levels and duration of hyperleptinemia as well as the presence of comorbidities such as diabetes have not yet been investigated as potential effect modifiers. We performed three interventional studies involving administration of recombinant methionyl human leptin (r-metHuLeptin) to lean, otherwise healthy obese, and obese diabetic subjects to investigate whether increasing circulating leptin levels over a wide spectrum of values (from low physiologic to high pharmacologic) would alter serum levels of inflammatory markers and other cytokines important in the T helper cell response. Increasing leptin levels from low physiologic to high physiologic in lean men and from higher physiologic to low pharmacologic in obese men over 3 d did not alter serum interferon-gamma, IL-10, TNF-alpha, monocyte chemoattractant protein-1, or soluble intercellular adhesion molecule-1. In obese subjects with type 2 diabetes mellitus, the administration of r-metHuLeptin for 4 or 16 wk, resulting in high pharmacologic leptin levels, did not activate the TNF-alpha system or increase cytokines or inflammatory markers, including IL-10, IL-6, C-reactive protein, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1. These findings do not support an etiopathogenic role for leptin in proinflammatory states associated with leptin excess such as obesity and have direct relevance for the potential future therapeutic use of r-metHuLeptin in humans.     

Predictive factors of excess body weight loss 1?year after laparoscopic bariatric surgery

Background

Bariatric surgery (BS) is widely accepted for the treatment of patients with morbid obesity (MO). We aimed to determine presurgical predictors of and surgical technique-related differences in excess weight loss (EWL) 1?year after BS.

Methods

This retrospective study included 407 subjects (F/M 3:1, median age?=?44?years) who underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n?=?307) or sleeve gastrectomy (SG, n?=?100) at our University Hospital and were evaluated 1?year after surgery.

Results

Baseline median (min–max) body mass index (BMI) was 47?kg/m² (range?=?36–71). BMI was higher in the SG than in the RYGB group (53 vs. 46?kg/m², p?p?p?=?0.2), was lower in diabetic than in nondiabetic subjects (71?±?17% vs. 79?±?17%, p?p?p?=?0.4) after taking into account baseline BMI. Multiple regression and logistic analysis showed that younger individuals with lower BMI but higher WC, and lower HbA1c and TG, had higher EWL and a higher rate of successful (EWL?≥?60%) weight loss.

Conclusions

Our data indicate that some of the characteristics that would have subjects referred early for BS were associated with higher weight loss. Therefore, the timing of laparoscopic BS might be an important factor for MO individuals in which medical weight loss intervention has failed.     

Flexibility in Processing Visual Information: Effects of Mood and Hypnosis

This quasi-experiment using a real/simulator model investigated differences in cognitive flexibility in high and low hypnotizable participants. Using the variables of hypnotizability (low/high), consciousness (nonhypnotized/hypnotized), mood (happy/sad), and visual-information processing (global/local), reaction times and target detection paradigms of the subjects were evaluated during both nonhypnotic and hypnotic states. Flexibility in cognitive processing was operationalized as the ability to overcome the typical global precedence and answer quickly about the nonprevalent local features. It was observed that the low hypnotizable participants were not influenced in their preference for the global or local dimension by any manipulated variable, whereas the high hypnotizables were more flexible.     

Analysis of gene expression profiles in melanoma cells with acquired resistance against antineoplastic drugs

Resistance to various antineoplastic agents is common in the clinical management of malignant melanoma. The biological mechanisms conferring these different drug-resistant phenotypes are still unclear. To identify potential factors mediating drug resistance to melanoma cells, the mRNA expression profiles of the parental drug-sensitive human melanoma cell line MeWo and four derived drug-resistant sublines with acquired resistance against four commonly used drugs for melanoma treatment (cisplatin, etoposide, fotemustine and vindesine) were analysed. We investigated cDNA arrays with 43,000 cDNA clones ( approximately 30,000 unique genes) to study the expression patterns of these cell lines. We were able to simultaneously extract new candidate genes associated with drug resistance in malignant melanoma and to correlate the present findings with previously described resistance-associated genes. Using hierarchical clustering and analysing the overlap of genes with altered expression, we detected similarities between the expression signatures related to cisplatin and fotemustine resistance. The resistance against vindesine required a minimal set of changes in gene expression relative to the parental MeWo cell line. Our study provides new data that may be used to obtain further insight into the resistance characteristics of malignant melanoma.     

Activation of the adenylyl cyclase/protein kinase A pathway facilitates neural release of beta-nicotinamide adenine dinucleotide in canine mesenteric artery

Using high performance liquid chromatography techniques with fluorescence detection we demonstrate that overflow of beta-nicotinamide adenine dinucleotide evoked by electrical field stimulation (16 Hz, 0.3 ms) in the canine isolated mesenteric artery is increased by the activators of adenylyl cyclase (AC) forskolin and calcitonin gene-related peptide (CGRP), by dibutyryl cAMP, and by the inhibitors of phosphodiesterases III and IV milrinone and rolipram. The enhancing effect of forskolin is abolished by the AC inhibitor MDL 12,330A and by protein kinase A (PKA) inhibitors peptide 14-22 amide and 4-cyano-3-methylisoquinoline. Therefore, activation of the AC/cAMP/PKA pathway enhances the release of beta-NAD+ from perivascular nerve terminals.