Treatment developments and the unfolding of the quality of life discussion in childhood medulloblastoma: a review

Purpose

To describe how the quality of life (QOL) discussion in childhood medulloblastoma (MB) relates to treatment developments, survival and sequelae from 1920 to 2014.

Methods

Articles containing “childhood medulloblastoma” and “quality of life” were identified in PubMed. Those containing phrases pertaining to psychological, emotional, behavioral or social adjustment in the title, abstract or keywords were selected. Inclusion of relevant older publications was assured by cross-checking references.

Results

1920–1930s: suction, electro-surgery, kilovolt (KV) irradiation. Survival = months. Focus on operative mortality, symptoms and survival. 1940s: radiotherapy improved. 1950s: chemotherapy and intubation. Survival = years. Opinions oscillated between optimism/awareness of physical sequelae of radiotherapy. 1960s: magnified vision, ventriculo-peritoneal (VP) shunts, megavolt (MV) irradiation. Long-term survival shifted the attention towards neurological problems, disability and carcinogenesis of radiotherapy. 1970s: CT, microscope, bipolar coagulation, shunt filters, neuroanesthesia, chemotherapy trials and staging studies. Operative mortality decreased and many patients (re)entered school; emphasis on neuropsychological sequelae, IQ and academic performance. 1980s: magnetic resonance imaging (MRI), Cavitron ultrasonic aspiration (CUSA), laser surgery, hyper-fractionated radiotherapy (HFRT). Cerebellar mutism, psychological and social issues. 1990s: pediatric neurosurgery, proton beams, stem cell rescue. Reflections on QOL as such. 21st century: molecular genetics. Premature aging, patterns of decline, risk- and resilience factors.

Discussion

QOL is a critical outcome measure. Focus depends on survival and sequelae, determined after years of follow-up. Detailed measurements are limited by time, money and human resources, and self-reporting questionnaires represent a crude measure limited by subjectivity. Therapeutic improvements raise the question of QOL versus cure. QOL is a potential primary research endpoint; multicenter international studies are needed, as are web-based tools that work across cultures.     

A dual-labeled Annexin A5 is not suited for SPECT imaging of brain cell death in experimental murine stroke

Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (AnxA5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled AnxA5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding AnxA5 or the nonfunctional AnxA5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled AnxA5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled AnxA5 appears to be unsuited for visualizing death of brain cells in this MCAO model.     

Cortical Porosity Identifies Women With Osteopenia at Increased Risk for Forearm Fractures

Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high‐resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10‐year fracture probability using the country‐specific fracture risk assessment tool (FRAX) in 68 postmenopausal women with forearm fractures and 70 age‐matched community controls in Olmsted County, MN, USA. Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact‐appearing cortical porosity predicted fracture independent of aBMD; odds ratio (OR) = 1.92 (95% confidence interval [CI] 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with fractures from those without because high porosity was present in 92% and 86% of each group, respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact‐appearing cortex conferred an OR for fracture of 4.00 (95% CI 1.15–13.90). In women with osteoporosis, porosity is captured by aBMD, so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. © 2014 American Society for Bone and Mineral Research.     

Changes in Sleep Disruption in the Treatment of Co‐Occurring Posttraumatic Stress Disorder and Substance Use Disorders

Sleep disruption appears not only to reflect a symptom of posttraumatic stress disorder (PTSD), but also a unique vulnerability for its development and maintenance. Studies examining the impact of psychosocial treatments for PTSD on sleep symptoms are few and no studies to date of which we are aware have examined this question in samples with co‐occurring substance use disorders. The current study is a secondary analysis of a large clinical trial comparing 2 psychological treatments for co‐occurring PTSD and substance use disorders. Women (N = 353) completed measures of PTSD at baseline, end of treatment, and 3‐, 6‐, and 12‐month follow‐ups. Results indicated that the prevalence of insomnia, but not nightmares, decreased during treatment, and that 63.8% of participants reported at least 1 clinical‐level sleep symptom at the end of treatment. Improvement in sleep symptoms during treatment was associated with better overall PTSD outcomes over time, χ²(1) = 33.81, p < .001. These results extend the existing literature to suggest that residual sleep disruption following PTSD treatment is common in women with co‐occurring PTSD and substance use disorders. Research on the benefits of adding sleep‐specific intervention for those with residual sleep disruption in this population may be a promising future direction.     

Prediction of peak oxygen uptake from differentiated ratings of perceived exertion during wheelchair propulsion in trained wheelchair sportspersons

Purpose

To assess the validity of predicting peak oxygen uptake ( $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ ) from differentiated ratings of perceived exertion (RPE) obtained during submaximal wheelchair propulsion.

Methods

Three subgroups of elite male wheelchair athletes [nine tetraplegics (TETRA), nine paraplegics (PARA), eight athletes without spinal cord injury (NON-SCI)] performed an incremental speed exercise test followed by graded exercise to exhaustion ( $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ test). Oxygen uptake ( $ {\dot{\text{V}}}{\text{O}}_2$ ), heart rate (HR) and differentiated RPE (Central RPE_C, Peripheral RPE_P and Overall RPE_O) were obtained for each stage. The regression lines for the perceptual ranges 9–15 on the Borg 6–20 scale ratings were performed to predict $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ .

Results

There were no significant within-group mean differences between measured $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ (mean 1.50 ± 0.39, 2.74 ± 0.48, 3.75 ± 0.33 L min^?1 for TETRA, PARA and NON-SCI, respectively) and predicted $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ determined using HR or differentiated RPEs for any group (P > 0.05). However, the coefficients of variation (CV %) between measured and predicted $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ using HR showed high variability for all groups (14.3, 15.9 and 9.7 %, respectively). The typical error ranged from 0.14 to 0.68 L min^?1 and the CV % between measured and predicted $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ using differentiated RPE was ≤11.1 % for TETRA, ≤7.5 % for PARA and ≤20.2 % for NON-SCI.

Conclusions

Results suggest that differentiated RPE may be used cautiously for TETRA and PARA athletes when predicting $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ across the perceptual range of 9–15. However, predicting $ {\dot{\text{V}}}{\text{O}}_{{\text{2peak}}}$ is not recommended for the NON-SCI athletes due to the large CV %s (16.8, 20.2 and 18.0 %; RPE_C, RPE_P and RPE_O, respectively).     

Is Borg’s perceived exertion scale a useful indicator of muscular and cardiovascular load in blue-collar workers with lifting tasks? A cross-sectional workplace study

Purpose

To investigate associations between perceived exertion and objectively assessed muscular and cardiovascular load during a full working day among workers with manual lifting tasks.

Methods

A total of 159 men and 41 women from 14 workplaces with manual lifting tasks participated. Participants reported perceived exertion (BORG-CR10) at midday and after work. Surface electromyography of the thigh, lower back and neck muscles were normalized to isometric voluntary contractions (MVC) to express relative muscle load during the day. Cardiovascular load was measured with electrocardiography and calculated as the average percentage of the heart rate reserve capacity (((heart rate during work – resting heart rate) / (maximum heart rate ? resting heart rate)) * 100) during the day.

Results

Using linear regression, significant but weak associations (β < 0.23) were observed between perceived exertion and (1) high muscle activity (>60 % of MVC) of the neck muscles and (2) inactivity (<1 % of MVC) of the thigh muscles and (3) cardiovascular load, respectively. Using logistic regression, perceived exertion ≥4 (high exertion), referencing <4 (low-to-moderate exertion), was related to high activity of the trapezius muscle [OR 18 (95 % CI 2–143)], i.e., the odds for experiencing high exertion during work increased 18-fold for each percentage increase in time above 60 % MVC.

Conclusions

During a full working day among blue-collar workers with lifting tasks, high neck muscle activity increases the odds for experiencing high perceived physical exertion. Perceived exertion of at least 4 on the BORG CR10 scale appears to be a good indicator that high muscular loading occurs.