Parametrized rectal dose and associations with late toxicity in prostate cancer radiotherapy

Objective:

We investigated possible associations between planned dose–volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy.

Methods:

For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose–volume (DVH), dose–surface (DSH) and dose–line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose–surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann–Whitney U test.

Results:

Associations (p < 0.05) were found between equieffective dose (EQD2₃) and late toxicity as follows: overall toxicity with DVH and DSH at 13–24 Gy; proctitis with DVH and DSH at 25–36 Gy and with DVH, DSH and DLH at 61–67 Gy; bowel urgency with DVH and DSH at 10–20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction.

Conclusion:

Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose–toxicity comparisons.

Advances in knowledge:

This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions.     

Dysphagia in cerebral palsy: A comparative study of the exeter dysphagia assesment technique and a multidisciplinary assessment

Eighteen children with cerebral palsy in a special school, most of whom had feeding difficulties, were studied to compare the diagnostic value of the Exeter Dysphagia Assessment Technique (EDAT) with an exhaustive clinical assessment undertaken by a multidisciplinary team experienced in the diagnosis and treatment of dysphagia of neurological origin. Four feeding skills were assessed by each method independently, viz. anticipation, intraoral sensory perception, oral-motor efficiency, and pharyngeal triggering. Comparison of the two sets of results showed agreement in at least 78% of the assessed skills. The possible reasons for the few discrepancies are discussed. The noninvasive EDAT equipment was easy to use with the children, who had a range of type and severity of cerebral palsy. The test was undertaken in their familiar surroundings and took 15 to 20 min per child. Interpretation of the results showed that EDAT provided a rapid, reliable diagnostic aid which assisted in the assessment of the degree of feeding impairment within each of the four feeding skills tested. The authors are very grateful for the financial support for this project which was provided partially by Action Research and partially by the Northcott Devon Medical Foundation     

Patient and Provider Attitudes Toward the Use of Patient Portals for the Management of Chronic Disease: A Systematic Review

Background

Patient portals provide patients with the tools to better manage and understand their health status. However, widespread adoption of patient portals faces resistance from patients and providers for a number of reasons, and there is limited evidence evaluating the characteristics of patient portals that received positive remarks from patients and providers.

Objective

The objectives of this systematic review are to identify the shared characteristics of portals that receive favorable responses from patients and providers and to identify the elements that patients and providers believe need improvement.

Methods

The authors conducted a systematic search of the CINAHL and PubMed databases to gather data about the use of patient portals in the management of chronic disease. Two reviewers analyzed the articles collected in the search process in order remove irrelevant articles. The authors selected 27 articles to use in the literature review.

Results

Results of this systematic review conclude that patient portals show significant improvements in patient self-management of chronic disease and improve the quality of care provided by providers. The most prevalent positive attribute was patient-provider communication, which appeared in 10 of 27 articles (37%). This was noted by both patients and providers. The most prevalent negative perceptions are security (concerns) and user-friendliness, both of which occurred in 11 of 27 articles (41%). The user-friendliness quality was a concern for patients and providers who are not familiar with advanced technology and therefore find it difficult to navigate the patient portal. The high cost of installation and maintenance of a portal system, not surprisingly, deters some providers from implementing such technology into their practice, but this was only mentioned in 3 of the 27 articles (11%). It is possible that the incentives for meaningful use assuage the barrier of cost.

Conclusions

This systematic review revealed mixed attitudes from patients and their providers regarding the use of patient portals to manage their chronic disease. The authors suggest that a standard patient portal design providing patients with the resources to understand and manage their chronic conditions will promote the adoption of patient portals in health care organizations.     

Prevalence, detection, management, and control of hypertension in Ashanti, West Africa

Hypertension and stroke are important threats to the health of adults in sub-Saharan Africa. Nevertheless, detection of hypertension is haphazard and stroke prevention targets are currently unattainable. Prevalence, detection, management, and control of hypertension were assessed in 1013 men (n=385) and women (n=628), both aged 55 [SD 11] years, living in 12 villages in Ashanti, Ghana. Five hundred thirty two lived in semi-urban and 481 in rural villages. The participants underwent measurements of height, weight, and blood pressure (BP) and answered a detailed questionnaire. Hypertension was defined as BP > or =140 and/or > or =90 mm Hg or being on drug therapy. Women were heavier than men. Participants in semi-urban areas were heavier and had higher BP (129/76 [26/14] versus 121/72 [25/13] mm Hg; P<0.001 for both) than in rural areas. Prevalence of hypertension was 28.7% overall and comparable in men and women, but higher in semi-urban villages (32.9% [95% CI 28.9 to 37.1] versus 24.1% [20.4 to 28.2]), and increased with age. Detection rate was lower in men than women (13.9% versus 27.3%; P=0.007). Treatment and control rates were low in both groups (7.8% and 4.4% versus 13.6% and 1.7%). Detection, treatment, and control rates were higher in semi-urban (25.7%, 14.3%, and 3.4%) than in rural villages (16.4%, 6.9%, and 1.7%). Hypertension is common in adults in central Ghana, particularly in urban areas. Detection rates are suboptimal in both men and women, especially in rural areas. Adequate treatment of high BP is at a very low level. There is an urgent need for preventive strategies on hypertension control in Ghana.     

Vaccinia Virus Induces Programmed Necrosis in Ovarian Cancer Cells

The mechanisms by which oncolytic vaccinia virus induces tumor cell death are poorly understood. We have evaluated cell death pathways following infection of ovarian cancer cells with both wild-type and thymidine kinase-deleted (dTK) Lister strain vaccinia. We show that death does not rely upon classical apoptosis despite the appearances of some limited apoptotic features, including phosphatidylserine externalization and appearance of sub-G1 DNA populations. Vaccinia infection induces marked lipidation of LC3 proteins, but there is no general activation of the autophagic process and cell death does not rely upon autophagy induction. We show that vaccinia induces necrotic morphology on transmission electron microscopy, accompanied by marked by reductions in intracellular adenosine triphosphate, altered mitochondrial metabolism, and release of high mobility group box 1 (HMGB1) protein. This necrotic cell death appears regulated, as infection induces formation of a receptor interacting protein (RIP1)/caspase-8 complex. In addition, pharmacological inhibition of both RIP1 and substrates downstream of RIP1, including MLKL, significantly attenuate cell death. Blockade of TNF-α, however, does not alter virus efficacy, suggesting that necrosis does not result from autocrine cytokine release. Overall, these results show that, in ovarian cancer cells, vaccinia virus causes necrotic cell death that is mediated through a programmed series of events.     

A multiple target neural transplantation strategy for Parkinson's disease

Intracerebral transplantation of embryonic ventral mesencephalic tissue is a potential treatment for patients with Parkinson's disease for whom medical management is unsatisfactory. Neural transplantation for parkinsonism has been studied experimentally in animal models of Parkinson's disease for more than two decades. These animal studies have shown significant graft survival, synapse formation, graft induced-dopamine release, and behavioural recovery in transplanted animals. Encouraged by these results, clinical programs have been initiated over the past 15 years; more than 250 patients worldwide have undergone neural transplantation. Both animal and clinical studies indicate that neural transplantation has the potential to become a valuable treatment option for Parkinson's disease. However, while many transplant recipients obtain clinically useful symptom relief, in all cases functional recovery is incomplete. Certain symptoms do not respond well to transplant therapy, and those symptoms that do typically do not resolve completely. This has spurred efforts to optimize the transplant procedure. One important approach is exploring novel methods such as multiple site transplantation. This transplantation strategy results in a more complete reinnervation of the dopaminergic circuitry that is affected in Parkinson's disease. In principle, multiple site transplantation should provide a more satisfactory resolution of symptoms. Here we review the progress made in multiple site neural transplantation for Parkinson's disease. The effects of intrastriatal, intranigral, intrasubthalamic nucleus, and intrapallidal grafts in animal models of Parkinson's disease are analysed. The current data suggest that intrastriatal grafts alone are inadequate to promote complete functional recovery. A multiple target strategy may restore dopaminergic input to affected basal ganglia nuclei and improve outcomes of neural transplantation in Parkinson's disease.     

The trypanocide diminazene aceturate is accumulated predominantly through the TbAT1 purine transporter: additional insights on diamidine resistance in african trypanosomes

Resistance to diminazene aceturate (Berenil) is a severe problem in the control of African trypanosomiasis in domestic animals. It has been speculated that resistance may be the result of reduced diminazene uptake by the parasite. We describe here the mechanisms by which [(3)H]diminazene is transported by Trypanosoma brucei brucei bloodstream forms. Diminazene was rapidly accumulated through a single transporter, with a K(m) of 0.45 +/- 0.11 micro M, which was dose dependently inhibited by pentamidine and adenosine. The K(i) values for these inhibitors were consistent with this transporter being the P2/TbAT1 adenosine transporter. Yeast expressing TbAT1 acquired the ability to take up [(3)H]diminazene and [(3)H]pentamidine. TbAT1-null mutants had lost almost all capacity for [(3)H]diminazene transport. However, this cell line still displayed a small but detectable rate of [(3)H]diminazene accumulation, in a nonsaturable manner. We conclude that TbAT1 mediates [(3)H]diminazene transport almost exclusively and that this explains the observed diminazene resistance phenotypes of TbAT1-null mutants and field isolates.