The power of Para sport: the effect of performance-focused swimming training on motor function in adolescents with cerebral palsy and high support needs (GMFCS IV) - a single-case experimental design with 30-month follow-up.

OBJECTIVE: This study aims to evaluate the effect of a performance-focused swimming programme on motor function in previously untrained adolescents with cerebral palsy and high support needs (CPHSN) and to determine whether the motor decline typical of adolescents with CPHSN occurred in these swimmers. METHODS: A Multiple-Baseline, Single-Case Experimental Design (MB-SCED) study comprising five phases and a 30-month follow-up was conducted. Participants were two males and one female, all aged 15 years, untrained and with CPHSN. The intervention was a 46-month swimming training programme, focused exclusively on improving performance. Outcomes were swim performance (velocity); training load (rating of perceived exertion min/week; swim distance/week) and Gross Motor Function Measure-66-Item Set (GMFM-66). MB-SCED data were analysed using interrupted time-series simulation analysis. Motor function over 46 months was modelled (generalised additive model) using GMFM-66 scores and compared with a model of predicted motor decline. RESULTS: Improvements in GMFM-66 scores in response to training were significant (p<0.001), and two periods of training withdrawal each resulted in significant motor decline (p≤0.001). Participant motor function remained above baseline levels for the study duration, and, importantly, participants did not experience the motor decline typical of other adolescents with CPHSN. Weekly training volumes were also commensurate with WHO recommended physical activity levels. CONCLUSIONS: Results suggest that adolescents with CPHSN who meet physical activity guidelines through participation in competitive swimming may prevent motor decline. However, this population is clinically complex, and in order to permit safe, effective participation in competitive sport, priority should be placed on the development of programmes delivered by skilled multiprofessional teams. TRIAL REGISTRATION NUMBER: ACTRN12616000326493.

Does sports-specific training improve measures of impairment developed for para sport classification? A multiple-baseline, single-case experiment.

Conceptually, sports-specific training should not influence measures of impairment used to classify Para athletes. This study evaluated the extent to which measures of strength, range of movement and coordination developed for Para swimming classification changed in response to a performance-focused swimming programme. A five-phase multiple-baseline, single-case experimental research design was utilized. Three participants with cerebral palsy and high support needs completed the 64-week study, which included two 16-week performance-focused swimming training blocks. Swimming speed, isometric shoulder extension strength, shoulder flexion range of movement and upper limb coordination were monitored throughout.Interrupted Time-Series Simulation Method analysis demonstrated large, significant changes in swimming speed (m/s) during the first (d = 2.17; 95% CI 0.45-3.88; p = 0.01) and second (d = 2.59; 95% CI 1.66-3.52; p = 0.00) training blocks. In contrast, changes in strength, range of movement and coordination were predominantly trivial and non-significant. This was the first study to investigate training responsiveness of measures developed for Para sport classification. Results indicate that despite significantly improved swimming performance, impairment measures remained relatively stable, and therefore these measures of impairment may be valid for the purposes of Para swimming classification. Further research is required in elite athletes, different sports and different impairment types.

Identifying Urinary Tract Infection-Related Information in Home Care Nursing Notes.

OBJECTIVES: Urinary tract infection (UTI) is common in home care but not easily captured with standard assessment. This study aimed to examine the value of nursing notes in detecting UTI signs and symptoms in home care. DESIGN: The study developed a natural language processing (NLP) algorithm to automatically identify UTI-related information in nursing notes. SETTING AND PARTICIPANTS: Home care visit notes (n = 1,149,586) and care coordination notes (n = 1,461,171) for 89,459 patients treated in the largest nonprofit home care agency in the United States during 2014. MEASURES: We generated 6 categories of UTI-related information from literature and used the Unified Medical Language System (UMLS) to identify a preliminary list of terms. The NLP algorithm was tested on a gold standard set of 300 clinical notes annotated by clinical experts. We used structured Outcome and Assessment Information Set data to extract the frequency of UTI-related emergency department (ED) visits or hospitalizations and explored time-patterns in documentation of UTI-related information. RESULTS: The NLP system achieved very good overall performance (F measure = 0.9, 95% CI: 0.87-0.93) based on the test results obtained by using the notes for patients admitted to the ED or hospital due to UTI. UTI-related information was significantly more prevalent (P < .01 for all the tests) in home care episodes with UTI-related ED admission or hospitalization vs the general patient population; 81% of home care episodes with UTI-related hospitalization or ED admission had at least 1 category of UTI-related information vs 21.6% among episodes without UTI-related hospitalization or ED admission. Frequency of UTI-related information documentation increased in advance of UTI-related hospitalization or ED admission, peaking within a few days before the event. CONCLUSIONS AND IMPLICATIONS: Information in nursing notes is often overlooked by stakeholders and not integrated into predictive modeling for decision-making support, but our findings highlight their value in early risk identification and care guidance. Health care administrators should consider using NLP to extract clinical data from nursing notes to improve early detection and treatment, which may lead to quality improvement and cost reduction.

Shaping the post-COVID-19 "New Normal" with Communication and Collaboration Platforms: state of the art communications for radiology, oncology, MDTs and beyond.

The COVID-19 pandemic has driven the use of digital communications to unprecedented levels across society whilst the NHS struggles with non-compatible IT systems that are often outdated and inhibit effective communication. MDTs use teleconferencing but the IT infrastructure does not permit clinicians to readily discuss cases and collaboratively review imaging outside of formal meetings if not on the same site and face-to-face. NHS radiology home reporting was not widely in place at the outbreak of the pandemic. Paper records persist further inhibiting remote working. Email has degraded the quality of written communication leading to suggestions of a 'broken' email culture. Despite NHS policy ambitions to address radiologist under capacity with increased networking and collaboration between providers the IT infrastructure has proven inadequate. Modern Communication and Collaboration Platforms have functionality that cuts across the non-compatible IT restrictions with screen sharing a key enabler. By engaging with these platforms radiologists and oncologists have a once-in-a-lifetime opportunity to shape the 'new normal' of delivery of healthcare with superior quality communication practices exceeding those in place at the outbreak of the pandemic.

Free-Text Documentation of Dementia Symptoms in Home Healthcare: A Natural Language Processing Study.

BACKGROUND: Little is known about symptom documentation related to Alzheimer's disease and related dementias (ADRD) by home healthcare (HHC) clinicians. OBJECTIVE: This study: (1) developed a natural language processing (NLP) algorithm that identifies common neuropsychiatric symptoms of ADRD in HHC free-text clinical notes; (2) described symptom clusters and hospitalization or emergency department (ED) visit rates for patients with and without these symptoms. METHOD: We examined a corpus of -2.6 million free-text notes for 112,237 HHC episodes among 89,459 patients admitted to a non-profit HHC agency for post-acute care with any diagnosis. We used NLP software (NimbleMiner) to construct indicators of six neuropsychiatric symptoms. Structured HHC assessment data were used to identify known ADRD diagnoses and construct measures of hospitalization/ED use during HHC. RESULTS: Neuropsychiatric symptoms were documented for 40% of episodes. Common clusters included impaired memory, anxiety and/or depressed mood. One in three episodes without an ADRD diagnosis had documented symptoms. Hospitalization/ED rates increased with one or more symptoms present. CONCLUSION: HHC providers should examine episodes with neuropsychiatric symptoms but no ADRD diagnoses to determine whether ADRD diagnosis was missed or to recommend ADRD evaluation. NLP-generated symptom indicators can help to identify high-risk patients for targeted interventions.

Fitness, Function, and Exercise Training Responses after Limb Salvage With a Lower Limb Megaprosthesis: A Systematic Review.

OBJECTIVE: To describe the fitness, function, and exercise training responses of patients following reconstruction of the lower limb with a total femoral (TF), proximal femoral (PF), distal femoral (DF), or proximal tibial (PT) megaprosthesis. TYPE: Systematic review. LITERATURE SURVEY: Five research databases were searched systematically for original studies published in English from 2006 to 2017 that reported fitness, functioning, or exercise training responses for one or more of the four types of lower limb megaprosthesis listed above. METHODOLOGY: Methodologic quality was assessed using a 22-item modified STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. SYNTHESIS: Of the 5342 articles retrieved, 28 met the inclusion criteria. Thirteen studies reported fitness outcomes, primarily in PT, with none in TF. Impaired knee extensor strength of the affected limb was reported following limb salvage with PF, DF, and PT megaprosthetics. Impaired flexibility was reported following limb salvage with DF and PT megaprosthetics. Functional outcomes were described in all studies and were most commonly reported using the Musculoskeletal Tumor Society (MSTS) system score. Results indicated no clear difference in functional outcomes between megaprosthesis locations. No studies evaluated exercise training responses. CONCLUSIONS: This review identified impairments of lower limb strength and flexibility following limb salvage with a lower limb megaprosthesis. Similarity in functional outcomes for all four reported megaprosthetic locations may indicate a lack of sensitivity in outcome measures, including the absence of items assessing higher-level functioning. Exercise interventions that aim to improve fitness and function in this population have not been evaluated but are required given increasing 5-year survival rates. LEVEL OF EVIDENCE: I.

Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.

BACKGROUND: Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. METHODS: The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061. FINDINGS: Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to receive either OSC plus WBRT (269) or OSC alone (269). Baseline characteristics were balanced between groups, and the median age of participants was 66 years (range 38-85). Significantly more episodes of drowsiness, hair loss, nausea, and dry or itchy scalp were reported while patients were receiving WBRT, although there was no evidence of a difference in the rate of serious adverse events between the two groups. There was no evidence of a difference in overall survival (hazard ratio 1·06, 95% CI 0·90-1·26), overall quality of life, or dexamethasone use between the two groups. The difference between the mean QALYs was 4·7 days (46·4 QALY days for the OSC plus WBRT group vs 41·7 QALY days for the OSC group), with two-sided 90% CI of -12·7 to 3·3. INTERPRETATION: Although the primary outcome measure result includes the prespecified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and quality of life between the two groups suggests that WBRT provides little additional clinically significant benefit for this patient group. FUNDING: Cancer Research UK, Medical Research Council Clinical Trials Unit at University College London, and the National Health and Medical Research Council in Australia.

Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.

BACKGROUND: The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial. METHODS: We did a multicentre, open-label, phase 3, randomised controlled trial in 22 UK hospitals of patients with histocytologically proven mesothelioma who had undergone large-bore pleural interventions in the 35 days prior to recruitment. Eligible patients were randomised (1:1), using a computer-generated sequence, to receive immediate radiotherapy (21 Gy in three fractions within 42 days of the pleural intervention) or deferred radiotherapy (same dose given within 35 days of PTM diagnosis). Randomisation was minimised by histological subtype, surgical versus non-surgical procedure, and pleural procedure (indwelling pleural catheter vs other). The primary outcome was the incidence of PTM within 7 cm of the site of pleural intervention within 12 months from randomisation, assessed in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN72767336. FINDINGS: Between Dec 23, 2011, and Aug 4, 2014, we randomised 203 patients to receive immediate radiotherapy (n=102) or deferred radiotherapy (n=101). The patients were well matched at baseline. No significant difference was seen in PTM incidence in the immediate and deferred radiotherapy groups (nine [9%] vs 16 [16%]; odds ratio 0·51 [95% CI 0·19-1·32]; p=0·14). The only serious adverse event related to a PTM or radiotherapy was development of a painful PTM within the radiotherapy field that required hospital admission for symptom control in one patient who received immediate radiotherapy. Common adverse events of immediate radiotherapy were skin toxicity (grade 1 in 50 [54%] and grade 2 in four [4%] of 92 patients vs grade 1 in three [60%] and grade 2 in two [40%] of five patients in the deferred radiotherapy group who received radiotherapy for a PTM) and tiredness or lethargy (36 [39%] in the immediate radiotherapy group vs two [40%] in the deferred radiotherapy group) within 3 months of receiving radiotherapy. INTERPRETATION: Routine use of prophylactic radiotherapy in all patients with mesothelioma after large-bore thoracic interventions is not justified. FUNDING: Research for Patient Benefit Programme from the UK National Institute for Health Research.

Continuous hyperfractionated accelerated radiotherapy - Escalated dose (CHART-ED): A phase I study.

INTRODUCTION: Patients who present with locally advanced inoperable non-small cell lung cancer (NSCLC) may be suitable for radical radiotherapy. A randomised trial of 563 patients compared CHART and conventional radical radiotherapy (60 Gy/30f) given over 6 weeks and suggested that CHART resulted in a 9% improvement in 2-year survival (Saunders et al., 1999). RT dose escalation for both conventional and CHARTWEL (CHART-WeekEndLess) - fractionation schedules is feasible with modern 3-dimensional CT-based planning techniques and we initiated a phase I CHART dose escalation study in 2009. METHODS: Patients with WHO performance status 0-2 histologically confirmed, inoperable, stage I-III non-small cell lung cancer were recruited into an open phase I dose escalation trial. Three cohorts of six patients were recruited sequentially. Total dose was escalated from standard CHART radiotherapy of 54 Gy/36f/12 days to 57.6G y (2 × 1.8 Gy fractions on day 15, Group 1), 61.2 Gy (4 × 1.8 Gy fractions on days 15-16, Group 2) and 64.8 Gy (6 × 1.8 Gy fractions on days 15-17, Group 3). RESULTS: Between April 2010 and May 2012, 18 patients were enrolled from 5 UK centres and received escalated dose radiotherapy. 14 were male, 16 squamous cell histology and 12 were stage IIIA or IIIB. The median age was 70 years and baseline characteristics were similar across the three dose cohorts. One patient did not start escalated radiotherapy but all remaining patients completed their planned radiotherapy schedules. Of these 9 patients have died to date with a median survival of 2 years across the three cohorts. Grade 3 or 4 adverse events (fatigue, dysphagia, nausea and anorexia - classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) were reported in 6 patients but the pre-specified dose limiting toxicities (grade 4 early oesophagitis; grade 3 cardiac, spinal cord and pneumonitis) were not observed. CONCLUSIONS: CHART remains a radiotherapy schedule in routine use across the UK and in this dose escalation study no dose limiting toxicities were observed. We feel the dose of 64.8 Gy/42f/17 days should be taken forward into further clinical trials. The sample size used in this study was small so we plan a randomised phase II study that includes other radiotherapy schedules to confirm safety and select an accelerated sequential chemo-radiotherapy schedule to take into phase III studies.

A Multicenter Randomized Trial of Ibandronate Compared With Single-Dose Radiotherapy for Localized Metastatic Bone Pain in Prostate Cancer.

BACKGROUND: The radiotherapy or ibandronate (RIB) trial was a randomized multicenter nonblind two-arm trial to compare intravenous ibandronate given as a single infusion with single-dose radiotherapy for metastatic bone pain. METHODS: Four hundred seventy prostate cancer patients with metastatic bone pain who were suitable for local radiotherapy were randomly assigned to radiotherapy (single dose, 8 Gy) or intravenous infusion of ibandronate (6mg) in a noninferiority trial. Pain was measured using the Brief Pain Inventory at baseline and four, eight, 12, 26, and 52 weeks. Pain response was assessed using World Health Organization (WHO) criteria and the Effective Analgesic Score (EAS); the maximum allowable difference was ±15%. Patients failing to respond at four weeks were offered retreatment with the alternative treatment. Quality of life (QoL) was assessed at baseline and four and 12 weeks. Because the trial was designed with a 5% one-sided test, we provide 90% confidence intervals (two-sided) for differences in pain response. RESULTS: Overall, pain response was not statistically different at four or 12 weeks (WHO: -3.7%, 90% confidence interval [CI] = -12.4% to 5.0%; and 6.7%, 90% CI = -2.6 to 16.0%, respectively). Corresponding differences using the EAS were -7.5% and -3.5%. However, a more rapid initial response with radiotherapy was observed. There was no overall difference in toxicity, although each treatment had different side effects. QoL was similar at four and 12 weeks. Overall survival was similar between the two groups but was better among patients having retreatment than those who did not. CONCLUSIONS: A single infusion of ibandronate had outcomes similar to a single dose of radiotherapy for metastatic prostate bone pain. Ibandronate could be considered when radiotherapy is not available.

A hybrid process fidelity assessment in a home-based randomized clinical trial.

A process fidelity assessment was conducted as a nested study within a home-based randomized clinical trial teaching self-management to 101 long-term indwelling urinary catheter users in the treatment group. Our hybrid model combined external assessments (outside observations and tape recordings) with internal evaluation methods (through study nurse forms and notes) for a comprehensive process fidelity assessment. Barriers, patient-related issues, and nurse perspectives were identified demonstrating the complexity in home care intervention research. The complementary and synergistic approaches provided in-depth information about the context of the delivery and the impact of the intervention on study outcomes.

Effect of re-irradiation for painful bone metastases on urinary markers of osteoclast activity (NCIC CTG SC.20U).

PURPOSE: The NCIC CTG Symptom Control.20 randomized trial (SC.20) confirmed the effectiveness of re-irradiation to painful bone metastases. This companion study correlates urinary markers of osteoclast activity with response to re-irradiation, survival and skeletal related events (SREs). METHODS: Pain response was assessed using the International Consensus Endpoints. Urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1month after re-irradiation were correlated to response to re-irradiation and then to both, either or none of the initial and re-irradiation: frequent responders (response to both); eventual responders (response to re-irradiation only); eventual non-responders (response to initial radiation only), and absolute non-responders (no response to both). RESULTS: Significant differences between 40 responders and 69 non-responders to re-irradiation existed for PYD (p=0.03) and DPD (p=0.04) at baseline. When patients were categorized as frequent responders (N=34), eventual responders (6), eventual non-responders (59) and absolute non-responders (10), the mean values of all markers in the absolute non-responders at baseline and the follow-up were about double those for the other three groups with statistically significant difference for DPD (p=0.03) at baseline. Absolute non-responders had the worst survival. The few occurrences of the SREs did not allow meaningful comparisons among the groups. CONCLUSION: There were significant differences between responders and non-responders to re-irradiation for PYD and DPD at baseline. The urinary markers in the absolute non-responders were markedly elevated at both baseline and follow-up with a statistically significant difference for DPD at baseline.

Protocol for the surgical and large bore procedures in malignant pleural mesothelioma and radiotherapy trial (SMART Trial): an RCT evaluating whether prophylactic radiotherapy reduces the incidence of procedure tract metastases.

INTRODUCTION: Patients with malignant pleural mesothelioma (MPM) may develop painful 'procedure tract metastasis' (PTM) at the site of previous pleural interventions. Prophylactic radiotherapy has been used to minimise this complication; however, three small randomised trials have shown conflicting results regarding its effectiveness. The surgical and large bore procedures in malignant pleural mesothelioma and radiotherapy trial (SMART Trial) is a suitably powered, multicentre, randomised controlled trial, designed to evaluate the efficacy of prophylactic radiotherapy within 42 days of pleural instrumentation in preventing the development of PTM in MPM. METHODS AND ANALYSIS: 203 patients with a histocytologically proven diagnosis of MPM, who have undergone a large bore pleural intervention (thoracic surgery, large bore chest drain, indwelling pleural catheter or local anaesthetic thoracoscopy) in the previous 35 days, will be recruited from UK hospitals. Patients will be randomised (1:1) to receive immediate radiotherapy (21 Gy in 3 fractions over 3 working days within 42 days of the pleural intervention) or deferred radiotherapy (21 Gy in 3 fractions over 3 working days given if a PTM develops). Patients will be followed up for 12 months. The primary outcome measure is the rate of PTM until death or 12 months (whichever is sooner), as defined by the presence of a clinically palpable nodule of at least 1 cm diameter felt within 7 cm of the margins of the procedure site as confirmed by two assessors. Secondary outcome measures include chest pain, quality of life, analgaesic requirements, healthcare utilisation and safety (including radiotherapy toxicity). ETHICS AND DISSEMINATION: The trial has received ethical approval from the Southampton B Research Ethics Committee (11/SC/0408). There is a Trial Steering Committee, including independent members and a patient and public representative. The trial results will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN72767336.

Hospital accreditation--a foundation for high reliability.

The people who work in health care organizations are committed to providing the best care possible to their patients. In the contemporary health care environment this is a very difficult commitment to keep. Health care has never been more complicated or demanding of the people who work in the industry. This article describes two different but complimentary methods for improving the quality and safety of health care. Accreditation provides a foundation for creating systems of care across many types of health care organizations. High reliability inspires people and organizations to strive for the highest levels of performance. Together, these methods give people working in health care an opportunity to fulfil their commitment to their patients.

Research on culturally tailored interventions aimed at improving chronic disease risk factors and management.

High blood pressure (HBP) is a worldwide epidemic with health and economic consequences. Although there is a growing body of knowledge, treatment options, and clinical guidelines, a small percentage of people with hypertension (HTN) achieve optimal control. In addition, HBP disproportionately affects racial and ethnic minorities. Strategies to address the management of HTN among specific populations remain scarce. Evidence shows that successful management of HTN requires pharmacological, educational, and self-care approaches. The first 3 summaries here profile research addressing this issue. The research focuses on the tailoring of interventions for racial and ethnic minority groups, specifically African Americans and Korean Americans. The fourth summary profiles an intervention targeted at a low-literacy group to improve diet. Readers are encouraged to access the full articles to learn more details about the intervention strategies and outcomes of these initiatives.

Evolutionary diversification indicated by compensatory base changes in ITS2 secondary structures in a complex fungal species, Rhizoctonia solani.

The rRNA cistron (18S-ITS1-5.8S-ITS2-28S) is used widely for phylogenetic analyses. Recent studies show that compensatory base changes (CBC) in the secondary structure of ITS2 correlate with genetic incompatibility between organisms. Rhizoctonia solani consists of genetically incompatible strain groups (anastomosis groups, AG) distinguished by lack of anastomosis between hyphae of strains. Phylogenetic analysis of internal transcribed spacer (ITS) sequences shows a strong correlation with AG determination. In this study, ITS sequences were reannotated according to the flanking 5.8S and 28S regions which interact during ribogenesis. One or two CBCs were detected between the ITS2 secondary structure of AG-3 potato strains as compared to AG-3 tobacco strains, and between these two strains and all other AGs. When a binucleate Rhizoctonia species related to Ceratobasidiaceae was compared to the AGs of R. solani, which were multinucleate (3-21 nuclei per cell), 1-3 CBCs were detected. The CBCs in potato strains of AG-3 distinguish them from AG-3 tobacco strains and other AGs yielding further evidence that the potato strains of AG-3 originally described as R. solani are a species distinct from other AGs. The ITS1-5.8S-ITS2 sequences were analyzed by direct sequencing of PCR products from 497 strains of AG-3 isolated from potato. The same 10 and 4 positions in ITS1 and ITS2, respectively, contained variability in 425 strains (86%). Nine different unambiguous ITS sequences (haplotypes) could be detected in a single strain by sequencing cloned PCR products indicating that concerted evolution had not homogenized the rRNA cistrons in many AG-3 strains. Importantly, the sequence variability did not affect the secondary structure of ITS2 and CBCs in AG-3.

Potential for higher treatment failure in obese patients: correlation of elevated body mass index and increased daily prostate deviations from the radiation beam isocenters in an analysis of 1,465 computed tomographic images.

PURPOSE: Recent clinical outcome studies on prostate cancer have reported the influence of patient's obesity on the biochemical failure rates after various treatment modalities. In this study, we investigated the effect of patient's physical characteristics on prostate shift in external beam radiotherapy (EBRT) and hypothesized that there maybe a correlation between patient physique and tumor shift. METHODS AND MATERIALS: A retrospective analysis was performed using data for 117 patients who received image-guided radiation therapy (IGRT) for prostate cancer between January 2005 and April 2007. A total of 1,465 CT scans were analyzed. The standard deviations (SDs) of prostate shifts for all patients, along with patient weight, body mass index (BMI), and subcutaneous adipose-tissue thickness (SAT), were determined. Spearman rank correlation analysis was performed. RESULTS: Of the 117 patients, 26.5% were considered normal weight, 48.7% were overweight, 17.9% were mildly obese, and 6.9% were moderately to severely obese. Notably 1.3%, 1.5%, 2.0%, and 21.2% of the respective shifts were greater than 10 mm in the left-right (LR) direction for the four patient groups, whereas in the anterior-posterior direction the shifts are 18.2%, 12.6%, 6.7%, and 21.0%, respectively. Strong correlations were observed between SAT, BMI, patient weight, and SDs of daily shifts in the LR direction (p < 0.01). CONCLUSIONS: The strong correlation between obesity and shift indicates that without image-guided radiation therapy, the target volume (prostate with or without seminal vesicles) may not receive the intended dose for patients who are moderate to severely obese. This may explain the higher recurrence rate with conventional external beam radiation therapy.

Inhibition of urinary bladder carcinogenesis by broccoli sprouts.

Isothiocyanates are a well-known class of cancer chemopreventive agents, and broccoli sprouts are a rich source of several isothiocyanates. We report herein that dietary administration to rats of a freeze-dried aqueous extract of broccoli sprouts significantly and dose-dependently inhibited bladder cancer development induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. The incidence, multiplicity, size, and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no histologic changes in the bladder. Moreover, inhibition of bladder carcinogenesis by the extract was associated with significant induction of glutathione S-transferase and NAD(P)H:quinone oxidoreductase 1 in the bladder, enzymes that are important protectants against oxidants and carcinogens. Isothiocyanates are metabolized to dithiocarbamates in vivo, but dithiocarbamates readily dissociate to isothiocyanates. We found that >70% of the isothiocyanates present in the extract were excreted in the urine as isothiocyanate equivalents (isothiocyanates + dithiocarbamates) in 12 h after a single p.o. dose, indicating high bioavailability and rapid urinary excretion. In addition, the concentrations of isothiocyanate equivalents in the urine of extract-treated rats were 2 to 3 orders of magnitude higher than those in plasma, indicating that the bladder epithelium, the major site of bladder cancer development, is most exposed to p.o. dosed isothiocyanate. Indeed, tissue levels of isothiocyanate equivalents in the bladder were significantly higher than in the liver. In conclusion, broccoli sprout extract is a highly promising substance for bladder cancer prevention and the isothiocyanates in the extract are selectively delivered to the bladder epithelium through urinary excretion.

The difficulties of a randomized study in superior vena caval obstruction.

INTRODUCTION: Superior vena caval obstruction (SVCO) is a not uncommon complication of malignant disease. Treatment may consist of radiation (RT) to the mediastinum, systemic therapy for chemosensitive tumors, and supportive measures such as oxygen and steroids. Advances in interventional radiology have allowed the introduction of expandable stents into the superior vena cava (SVC), with the theoretical advantage of providing symptom relief within hours, rather than the days and weeks over which RT exerts its effect. Although small case series have supported the use of stents in SVCO, there are no randomized data. METHODS: We set up a randomized study at Princess Margaret Hospital, Toronto. Patients were randomized to receive palliative RT to the mediastinum or immediate stenting of the SVC and then mediastinal RT within a week. The aim of the study was to compare symptom response between the two treatment arms. A second study, a prospective longitudinal study, was also set up to obtain information on symptom response and outcome regardless of the treatment given. RESULTS: In a 12-month period, we were unable to accrue any patients in the randomized study; of the 19 patients approached, 13 have agreed to participate in the longitudinal study. CONCLUSIONS: In this report, we present the problems that we have encountered with these studies.