Chronic pain, fatigue, and depressive symptoms in adults with spastic bilateral cerebral palsy

Aim To investigate the prevalence and co-occurrence of chronic pain, fatigue, and depressive symptoms in adults with spastic bilateral cerebral palsy (SBCP) and explore associations of chronic pain and fatigue with depressive symptoms and daily functioning. Method Fifty-six adults with SBCP without severe cognitive impairment participated (35 males, 21 females; mean age 36y 5mo, SD 5y 10mo; Gross Motor Function Classification System level I [13], II [28], III [11], IV [4]). Chronic pain (>3mo), severity and nature of fatigue (Fatigue Severity Scale; Multidimensional Fatigue Inventory), and depressive symptoms (Center for Epidemiological Studies Depression Scale) were assessed. Associations were explored using multivariable logistic regression analyses. Results The study sample had a higher prevalence of chronic pain (75% vs 39%; p<0.001), mean fatigue (Fatigue Severity Scale, 4.4 [SD 1.3] vs 2.9 [SD 1.1]; p<0.001), and prevalence of depressive symptoms (25% vs 12%; p=0.004) than Dutch healthy reference samples. Chronic pain and severe fatigue co-occurred in 34% and in combination with depressive symptoms in 16% of the participants. Severity of fatigue was associated with depressive symptoms (OR 3.38; p<0.01). Chronic pain and fatigue were not associated with limitations in daily functioning. Interpretation These findings suggest that adults with SBCP are severely affected by chronic pain, fatigue, and depressive symptoms, in addition to their spastic paresis.     

Uncertainty in health care: Towards a more systematic program of research

ObjectiveTo promote a more systematic approach to research on uncertainty in health care, and to explore promising starting points and future directions for this research.MethodsWe examine three fundamental aspects of medical uncertainty that a systematic research program should ideally address: its nature, effects, and communication. We summarize key insights from past empirical research and explore existing conceptual models that can help guide future research.ResultsA diverse body of past research on medical uncertainty has produced valuable empirical insights and conceptual models that provide useful starting points for future empirical and theoretical work. However, these insights need to be more fully developed and integrated to answer remaining questions about what uncertainty is, how it affects people, and how and why it should be communicated.ConclusionUncertainty in health care is an extremely important but incompletely understood phenomenon. Improving our understanding of the many important aspects of uncertainty in health care will require a more systematic program of research based upon shared, integrative conceptual models and active, collaborative engagement of the broader research community.Practice ImplicationsA more systematic approach to investigating uncertainty in health care can help elucidate how the clinical communication of uncertainty might be improved.     

Chemically synthesized protein as tumour-specific vaccine: immunogenicity and efficacy of synthetic HPV16 E7 in the TC-1 mouse tumour model

Many successful candidate vaccines capable of combating tumours in animal models come to an untimely end because of the costs associated with the approval and production of the GMP-grade materials, which are usually of biological origin, for use in humans. We have used a GMP-compatible method to chemically synthesize a pure synthetic E7 protein of the human papillomavirus type 16 (HPV16-E7). This oncogen-derived protein is constitutively expressed in cervical cancer and its precursors and is thus considered as an excellent target for tumour-specific immunity. Injection of a mixture of the synthetic HPV16-E7 protein and the synthetic adjuvant CpG in mice resulted in strong functional HPV16-specific cytotoxic T-lymphocyte responses as measured by CD8+ MHC class I-tetramer staining, the detection of antigen-specific intracellular IFNgamma production and the ability to protect mice against a challenge with HPV16-E7+ TC-1 tumour cells in both prophylactic and therapeutic vaccination regimens. Our results demonstrate the potential use of pure synthetic vaccines that can be efficiently produced under GMP at low cost, which will stimulate the translation of new vaccination strategies into phase I/II clinical trials.     

Genetic analysis of physical activity in twins

BACKGROUND: The reduced contribution of physical activity (PA) to daily energy expenditure contributes to the increased prevalence of obesity. A genetic control of activity-induced energy expenditure (AEE) may contribute to a genetic susceptibility to obesity. OBJECTIVE: Our aim was to investigate the relative contribution of genetic and environmental factors to the variation and covariation in AEE and PA. DESIGN: Twelve monozygotic and 8 same-sex dizygotic (including 2 same-sex sibling pairs; age differences: 2 and 2.5 y) twin pairs aged between 18 and 39 y participated. AEE was measured in a respiration chamber for 24 h and with doubly labeled water in daily life for 2 wk. PA was recorded simultaneously with a triaxial accelerometer. Structural equation modeling was used to separate and quantify the observed variance into sex-adjusted additive genetic and common and unique environmental contributions. RESULTS: In the respiration chamber, common and unique environmental factors explained the variance in AEE and PA, and no genetic contribution was found. In daily life, genetic factors explained 72% of the variance in AEE and 78% of the variance in PA. Unique environmental factors explained the remaining variance. The same additive genetic factors explained 67% of the covariance in AEE and PA in daily life. CONCLUSIONS: In the present exploratory study that used gold standard measurements for AEE and PA but a limited sample size, genetic influence explained a large part of the variation in AEE and PA in daily life, whereas both AEE and PA were influenced by environment only within the confined area of the respiration chamber.     

Treatment failure in patients with HPV 16-induced vulvar intraepithelial neoplasia: understanding different clinical responses to immunotherapy

Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.     

Validation of the English version of the Trust in Oncologist Scale (TiOS)

Objective

The Trust in Oncologist Scale (TiOS) was recently developed and validated in The Netherlands to assess cancer patients’ trust in their oncologist. In this study, we translated and further validated the scale amongst English-speaking Australian cancer patients, to establish cross-cultural validity.

Methods

The translated 18-item scale was administered to cancer patients (n = 175) from three Sydney hospitals. In addition to trust, we assessed patients’ satisfaction, trust in health care, and background characteristics. Dimensionality, internal consistency, and construct validity of the translated scale were assessed.

Results

Psychometric properties of all items were acceptable. Trust scores were very high. Factor analyses indicated one-dimensionality of the scale. Internal consistency was strong. Moderate to high correlations were found between trust (TiOS) and its known correlates, i.e., satisfaction, number of previous consultations with the oncologist, and trust in health care, indicating good construct validity.

Conclusion

Trust is highly coherent, suggesting that cancer patients do not distinguish between separate dimensions of trust. Future research could clarify if trust is equally strong and one-dimensional among specific groups of cancer patients.

Practice implications

Both the English and the Dutch Trust in Oncologist Scales appear suitable for assessing cancer patients’ trust reliably and validly.     

Improved peptide vaccine strategies, creating synthetic artificial infections to maximize immune efficacy

Soon after it was realized that T-cells recognize their target antigens as small protein fragments or peptides presented by MHC molecules at the cell surface, these peptide epitopes have been tried as vaccines. Human testing of such vaccines, although protective in mouse models, has produced mixed results. Since these initial trials, there has been an tremendous increase in our understanding of how infectious organisms can induce potent immune responses. In this article we review the key changes in the design, formulation and delivery of synthetic peptide vaccines that are applied to improve peptide vaccine strategies.