A multi institutional comparison of imaging dose and technique protocols for neonatal chest radiography.

INTRODUCTION: The focus on paediatric radiation dose reduction supports reevaluation of paediatric imaging protocols. This is particularly important in the neonates where chest radiographs are frequently requested to assess respiratory illness and line placement. This study aims to assess the impact of neonatal chest radiographic protocols on patient dose in four hospitals in different countries. METHODS: Exposure parameters, collimation, focus to skin distance (FSD) and radiation dose from 200 neonatal chest radiographs were registered prospectively. Inclusion criteria consisted of both premature and full-term neonates weighing between 1000 and 5000 g. Only data from the examinations meeting diagnostic criteria and approved for the clinical use were included. Radiation dose was assessed using dose area product (DAP). RESULTS: The lowest DAP value (4.58 mGy cm2) was recorded in the Norwegian hospital, employing a high kVp, low mAs protocol using a DR system. The Canadian hospital recorded the highest DAP (9.48), using lower kVp and higher mAs with a CR system, including the addition of a lateral projection. The difference in the mean DAP, weight, field of view (FOV) and kVp between the hospitals is statistically significant (p < 0.001). CONCLUSION: Use of non-standardised imaging protocols in neonatal chest radiography results in differences in patient dose across hospitals included in the study. Using higher kVp, lower mAs and reducing the number of lateral projections to clinically relevant indications result in a lower DAP measured in the infant sample studied. Further studies to examine image quality based on exposure factors and added filtration are recommended. IMPLICATIONS FOR PRACTICE: Reevaluation of paediatric imaging protocols presents an opportunity to reduce patient dose in a population with increased sensitivity to ionising radiation.

Can contrast-enhanced MRI with gadoxetic acid predict liver failure and other complications after major hepatic resection?

AIM: To determine whether a combination of clinical factors, the future liver remnant (FLR) ratio, and hepatic uptake of gadoxetic acid can be used to predict post-hepatectomy liver failure (PHLF) and other major complications (OMC). MATERIALS AND METHODS: Sixty-five consecutive patients who underwent pre-hepatectomy gadoxetic acid-enhanced magnetic resonance imaging (MRI) between October 2010 and December 2013 were included. The relative liver enhancement (RLE) of gadoxetic acid was calculated from regions of interest on MRI, and FLR ratios were obtained from computed tomography (CT). PHLF and OMC were defined by the International Study Group of Liver Surgery criteria and Clavien-Dindo grade of ≥3, respectively. Multivariate logistic regression modelling was performed to identify predictors of PHLF and OMC, including RLE, FLR ratio, age, sex, chemotherapy history, intra-operative blood loss, and intra-operative transfusion. RESULTS: Nine patients experienced PHLF and another nine patients experienced OMC. RLE was comparable to the FLR ratio in predicting PHLF (areas under the receiver operating characteristic [AUROC] curves, 0.665 and 0.705), but performed poorly in predicting OMCs (AUROCs, 0.556 and 0.702). Combining all clinical and imaging parameters as predictors yielded the best performing predictive models (AUROCs, 0.875 and 0.742 for PHLF and OMC, respectively). CONCLUSION: A model based on clinical parameters, the FLR ratio, and RLE of gadoxetic acid may improve pre-hepatectomy risk assessment.

The Toronto Western Hospital catheter: one center's experience and review of the literature.

BACKGROUND: We report our center's experience with the Toronto Western Hospital (TWH) catheter, and discuss our catheter survival and complication rates. METHODS: Retrospective chart review of patients receiving peritoneal dialysis therapy via a TWH catheter. Catheter complication rates of peritonitis, exit site infection, obstruction, leak, and malfunction were assessed. A catheter was considered failed if removed because of exit site infection, obstruction, or malfunction. All other catheters, even if removed for other reasons, were considered censured. Survival was defined as the period from insertion to failure or censure date, and reported using Kaplan Meier analysis. RESULTS: 192 patients with a total of 208 TWH catheters (4,845.3 catheter months) were analyzed. Our overall 1- and 3-year catheter survival rates were identical at 0.9182. Our catheter complication rates (expressed as number of catheter months per event) were 31.3 for peritonitis, 42.9 for exit site infection, 72.3 for obstruction, 538.4 for malfunction, and 969.1 for catheter leak. Our findings were similar to those reported in the literature for TWH and other peritoneal catheters.

A survey of factor prophylaxis in boys with haemophilia followed in North American haemophilia treatment centres.

A survey was conducted in 2002 to determine the pattern of factor prophylaxis use in boys or=45 weeks per year, was significantly higher for haemophilia A vs. haemophilia B cases (51% vs. 32%, P< 0.0001), and for boys with severe haemophilia A living in Canada vs. the USA (77% vs. 47%, P< 0.0001). Use of full-dose prophylaxis, defined as the infusion of 25-40 IU kg(-1) of factor VIII on alternate days (minimum three times per week) or 25-40 IU kg(-1) of factor IX twice weekly, was similar for boys

A modified protocol for the assessment of visual function in patients with retinitis pigmentosa.

BACKGROUND: The assessment of visual function for retinitis pigmentosa routinely includes: electroretinography, visual acuity and visual field-testing. Patients with retinitis pigmentosa sometimes complain of changes in visual function, which are not paralleled by routine eye tests. AIMS AND OBJECTIVES: To determine which visual function test or group of tests can predict reliably perceived visual function in patients with retinitis pigmentosa METHODS: Subjects with progressive retinitis pigmentosa are recruited from the Ocular genetics program of The Hospital for Sick Children and Mount Sinai Hospital, Toronto. Subjects will be tested four times over the over the period of one year. On each visit they undergo following tests- 1) Central visual acuity (VA) using the crowded logMAR acuity chart, 2) Contrast Sensitivity (CS) using Pelli-Robson contrast sensitivity chart, 3) Visual field test (VF) using Humphrey (10-2), 4) Color vision using Mollon-Reffin 'minimalist' test and 5) Subjective visual function questionnaire testing near and global perceived visual function respectively. RESULTS: Phase I (baseline and visit I measure) results are reported. Total of sixty-eight patients with mean age of 41 years, age range of twelve to sixty seven were tested. Of these thirty-one were males and thirty-seven were females. Repeat testing correlation was high (r>0.8, p<0.05) for all parameters between baseline visit and visit I. The near perceived visual function correlated best with the combination of visual acuity and contrast sensitivity. The global perceived visual function correlated best with combination of visual field and visual acuity. Objective measure of central visual function (HVF 10-2) correlated best with contrast sensitivity. DISCUSSION: The addition of contrast sensitivity and Humphrey visual field to routine visual assessment should improve the quality of the longitudinal data of visual function recorded on these patients. Patients will be re- tested at six months and one-year interval. To date of the sixty-eight subjects twenty-seven have returned for their six-month visit (phase II).

Binary partitioning for continuous longitudinal data: categorizing a prognostic variable.

We investigate a binary partitioning algorithm in the case of a continuous repeated measures outcome. The procedure is based on the use of the likelihood ratio statistic to evaluate the performance of individual splits. The procedure partitions a set of longitudinal data into two mutually exclusive groups based on an optimal split of a continuous prognostic variable. A permutation test is used to assess the level of significance associated with the optimal split, and a bootstrap confidence interval is obtained for the optimal split.

Long-term medical outcomes and quality-of-life assessment of patients with chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow transplantation.

PURPOSE: Benchmark analysis of patients with chronic myeloid leukemia (CML) alive for more than 10 years after allogeneic bone marrow transplantation (BMT) including data on disease status, bone marrow reserve, long-term complications, and quality of life (QOL). PATIENTS AND METHODS: Eighty-nine patients (46 in first chronic phase, 43 in advanced phase) received an allogeneic BMT for CML during the study period. Medical outcomes and QOL of patients were analyzed retrospectively. RESULTS: Twenty-eight (31.5%) of 89 patients were alive at 10 years and included in this analysis. Thirteen (46.4%) of 28 long-term survivors never relapsed. Fifteen patients relapsed between 0.5 and 16 years after transplantation. Ten patients showed a hematologic relapse and received salvage treatment. Five patients showed transient low levels of BCR-ABL-positive cells by Southern blot with no subsequent hematologic relapse. One of the 28 patients died in blast crisis at 12 years. The most frequent long-term complications were chronic graft-versus-host disease, osteoporosis, and cataracts. Frequency of clonogenic progenitors remained persistently decreased. QOL assessment yielded lower scores in physical performance as compared with an age-matched normative population, whereas social functioning was equivalent. A high degree of satisfaction was noted with interpersonal relationships. CONCLUSION: Patients with CML surviving their BMT long term do well in terms of medical outcomes. A constant rate of relapse was noted, with a high salvage rate of affected patients, suggesting the need for lifelong monitoring. QOL is perceived as good, particularly as related to social functioning; however, it is inferior to a normative population with regard to physical performance.

Visual results in children treated for macular retinoblastoma.

PURPOSE: To evaluate the results of patching treatment in children with macular retinoblastoma in one eye. METHODS: Fifteen children affected by macular retinoblastoma received instructions for patching treatment for amblyopia. Data were collected on age at diagnosis of the tumor, presence of unilateral or bilateral disease, area of posterior pole involvement by the scar of the regressed tumor and its relationship to the fovea; and the onset, duration, and compliance of patching. The visual acuities recorded were expressed in logMAR (logarithm minimum angle of resolution) equivalents. RESULTS: Twelve children (80%) had bilateral retinoblastoma with the macular involved in one eye and three children had unilateral macular tumors. The median age at which patching was initiated was 15 months (range 4-36). Compliance to patching was good in 80% of children, with a median duration of 4 h (range 0.5-8) per day, 7 days per week, with total occlusion of the better eye. The median percentage of posterior pole involvement was 34% (range 11-100%). Eighty percent of children had some improvement in their visual acuity, and of the children in whom final logMAR acuity was recorded, 73% had an acuity of 1.0 logMAR or better and 53% an acuity of 0.5 logMAR or better after patching. There was no evidence of association between age of patient, sex, duration of patching, or percentage of posterior pole involvement and the improvement in visual acuity. CONCLUSIONS: In spite of the macular involvement of eyes with retinoblastoma, some visual recovery was achieved in 80% of children. Hence a trial of patching therapy is recommended for all children with involvement of the macula by retinoblastoma.

Positioning errors and prostate motion during conformal prostate radiotherapy using on-line isocentre set-up verification and implanted prostate markers.

PURPOSE: To evaluate treatment errors from set-up and inter-fraction prostatic motion with port films and implanted prostate fiducial markers during conformal radiotherapy for localized prostate cancer. METHODS: Errors from isocentre positioning and inter-fraction prostate motion were investigated in 13 men treated with escalated dose conformal radiotherapy for localized prostate cancer. To limit the effect of inter-fraction prostate motion, patients were planned and treated with an empty rectum and a comfortably full bladder, and were instructed regarding dietary management, fluid intake and laxative use. Field placement was determined and corrected with daily on-line portal imaging. A lateral portal film was taken three times weekly over the course of therapy. From these films, random and systematic placement errors were measured by matching corresponding bony landmarks to the simulator film. Superior-inferior and anterior-posterior prostate motion was measured from the displacement of three gold pins implanted into the prostate before planning. A planning target volume (PTV) was derived to account for the measured prostate motion and field placement errors. RESULTS: From 272 port films the random and systematic isocentre positioning error was 2.2 mm (range 0.2-7.3 mm) and 1.4 mm (range 0.2-3.3 mm), respectively. Prostate motion was largest at the base compared to the apex. Base: anterior, standard deviation (SD) 2.9 mm; superior, SD 2.1 mm. Apex: anterior, SD 2.1 mm; superior, SD 2.1 mm. The margin of PTV required to give a 99% probability of the gland remaining within the 95% isodose line during the course of therapy is superior 5.8 mm, and inferior 5.6 mm. In the anterior and posterior direction, this margin is 7.2 mm at the base, 6.5 mm at the mid-gland and 6.0 mm at the apex. CONCLUSIONS: Systematic set-up errors were small using real-time isocentre placement corrections. Patient instruction to help control variation in bladder and rectal distension during therapy may explain the observed small SD for prostate motion in this group of patients. Inter-fraction prostate motion remained the largest source of treatment error, and observed motion was greatest at the gland base. In the absence of real-time pre-treatment imaging of prostate position, sequential portal films of implanted prostatic markers should improve quality assurance by confirming organ position within the treatment field over the course of therapy.

Local excision and postoperative radiotherapy for distal rectal cancer.

PURPOSE: To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma. MATERIALS AND METHODS: Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and "elective" where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1--8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38--60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3--5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10--165 months). RESULTS: Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery). CONCLUSION: The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.

The effects of age of cochlear implantation on speech perception outcomes in prelingually deaf children.

We have made a retrospective analysis on 70 prelingually deaf children (78% congenital; age range 2-15 years) followed for up to 5 years post-implant during which both closed set speech perception tests (TAC, WIPI) and open set tasks (PBK, GASP) were administered. We used a binary partitioning algorithm to optimally divide our dataset on the basis of age at implantation This technique achieves an optimal split when the heterogeneity of the data is most reduced (maximal drop in deviance). For the closed set speech perception tests (TAC and WIPI) partitioning best divided-out data at age 4.4 years. For the open set tests optimal division was at a higher age of implantation (GASP word, 5.6 years; PBK word, 8.4 years). Using these partitioning values, we have found statistically significant differences between rate of improvement of scores in the younger implanted children compared with those implanted later.

Postradiotherapy prostate biopsies: what do they really mean? Results for 498 patients.

PURPOSE: Postradiotherapy (RT) prostate biopsies are prone to problems in interpretation. False negatives due to sampling error, false positives due to delayed tumor regression, and indeterminate biopsies showing radiation effect in residual tumor of uncertain viability are common occurrences. METHODS AND MATERIALS: A cohort of 498 men treated with conventional RT from 06/87-10/96 were followed prospectively with systematic transrectal ultrasound (TRUS)-guided post-RT prostate biopsies, starting 12-18 months after RT. If there was residual tumor but further decline in serum prostate-specific antigen (PSA), biopsies were repeated every 6-12 months. Patients with negative biopsies were rebiopsied at 36 months. Residual tumor was evaluated for RT effect and proliferation markers. The 498 men had 978 biopsies. Median time of the first biopsy (n = 498) was 13 months, biopsy #2 (n = 342) 28 months, biopsy #3 (n = 110) 36 months, biopsy #4 (n = 28) 44 months, and biopsy #5 (n = 4) 55 months. Median follow-up is 54 months (range 13-131). One hundred seventy-five patients (34%) had prior hormonal therapy for a median of 5 months (range 1-60). RESULTS: Clinical stage distribution was T1b: 46; T1c: 50; T2a: 115; T2b/c: 170; T3: 108; T4: 11; Tx: 1. Distribution by Gleason score was: 28% Gleason score 2-4; 42%: 5-6; 18%: 7; and 12%: 8-10. Seventy-one men have died, 26 of prostate cancer and 45 of other causes. Actuarial failure-free survival by T stage at 5 years is T1b: 78%; T1c: 76%; T2a: 60%; T2b/c: 55%; T3: 30%; and T4: 0%. Actuarial freedom from local failure at 5 years is T1b: 83%; T1c: 88%; T2a: 72%; T2b/c: 66%; T3: 58%; and T4: 0%. The proportion of indeterminate biopsies decreases with time, being 33% for biopsy 1, 24% for biopsy 2, 18% for biopsy 3, and 7% for biopsy 4. Thirty percent of indeterminate biopsies resolved to NED status, regardless of the degree of RT effect, 18% progressed to local failure, and 34% remained as biopsy failures with indeterminate status within the time frame of this report. Positive staining for proliferation markers was associated with both subsequent local failure and also any type of failure. In multivariate analysis, only PSA nadir (p = 0.0002) and biopsy status at 24-36 months (p = 0. 0005) were independent predictors of outcome. CONCLUSIONS: Post-RT prostate biopsies are not a gold standard of treatment efficacy, but are an independent predictor of outcome. Positive immunohistochemical staining for markers of cellular proliferation is associated with subsequent local failure. Indeterminate biopsies, even when showing marked RT effect, cannot be considered negative.

Cognitive function in breast cancer patients receiving adjuvant chemotherapy.

PURPOSE: Breast cancer patients receiving chemotherapy have complained of difficulties in their ability to remember, think, and concentrate. This study assessed whether there are differences in cognitive function between breast cancer patients treated with standard-dose adjuvant chemotherapy compared with healthy controls. PATIENTS AND METHODS: The High Sensitivity Cognitive Screen and the Profile of Mood States (POMS) were used to assess cognitive function and mood in a group of 107 women. The women consisted of 31 breast cancer patients receiving adjuvant chemotherapy (group A), 40 breast cancer patients who had completed adjuvant chemotherapy a median of 2 years earlier (group B), and 36 healthy controls (group C). RESULTS: Univariate analysis showed statistically significant differences (P =.009) in overall cognitive function scores between groups A and C, with poorer function in patients receiving adjuvant chemotherapy. These differences remained significant (P =.046) when controlling for age, education level, and menopausal status. More patients had moderate or severe cognitive impairment in groups A and B than in controls (P

Perceptions of Ashkenazi Jewish breast cancer patients on genetic testing for mutations in BRCA1 and BRCA2.

The perceived benefits and risks of genetic testing may vary between groups of individuals with different cultural, demographic, and family history features. This multicentre study examined the factors that influenced the decision to undergo genetic testing for BRCA1 and BRCA2 in Canadian Jewish women with breast cancer. A self-administered questionnaire was developed and distributed to 134 individuals enrolled in a research-based testing program for Ashkenazi women. The questionnaire assessed demographic, social, and family history parameters, and the influence of medical, family, social, psychological, and cultural/religious factors on decision making about genetic testing. Seventy-six percent of women completed the questionnaire. Forty-one percent of study participants had no family history of breast or ovarian cancer. The most important factors influencing the decision to undergo testing were a desire to contribute to research, potential benefit to other family members, curiosity, and the potential for relief if not found to be a carrier (endorsed by 87, 78, 70, and 60% of participants, respectively). The main perceived risks of undergoing genetic testing related to insurance discrimination, confidentiality, accuracy and interpretability of results, potential impact on marriage prospects for family members, and focus on the Jewish community (endorsed by 28, 24, 30, 17, and 14% of participants, respectively). This study provides novel information on the motivating factors for BRCA1 and BRCA2 mutation testing in Canadian women of Ashkenazi Jewish descent. The focus on altruistic factors and those related to perceived psychological benefits of testing is notable.

Liarozole fumarate (R85246): in the treatment of ER negative, tamoxifen refractory or chemotherapy resistant postmenopausal metastatic breast cancer.

Three phase II studies were conducted to determine the efficacy and tolerability of liarozole fumarate (R85246; liarozole), a retinoic acid metabolism blocking agent (RAMBA) and aromatase inhibitor. Additionally, animal experiments in the MNU-induced rat mammary tumor model and in immature ovariectomized rats were conducted to further elucidate liarozole's mechanisms of action. Patients were postmenopausal with either: ER negative disease in first relapse (Group 1: 1n = 16); ER positive or unknown disease refractory to tamoxifen (Group 2; n = 16); ER positive, negative or unknown disease resistant or refractory to chemotherapy (Group 3; n = 27). Treatment was liarozole (150-300mg) twice daily orally until disease progression. Response rates were: 25% in group 1 (95% CI 11.0-52.3%: median duration (MD) 20 months; range 2-36.5); 25% in group 2 (95% CI 11.0-52.3%; MD 6.5 months: range 3.5-38): 11% in group 3 (95% CI 4.2-29.2%; MD 7 months; range 3-8.5). No significant improvement in quality of life scores (FLI-C) was noted. Toxicities observed were predominantly dermatological (skin disorders: 88%; dry mouth/eyes/lips: 69%). Plasma estradiol decreased from mean pre-treatment levels of 72.7 pM (9.1-1,839 pM) to below detection (9.2 pM) after 1 month. Liarozole, but not vorozole, partially inhibited estradiol induced uterine hypertrophy and demonstrated dose-dependent anti-tumor effects in the rats, only partially overcome by coadministration of estradiol. The clinical responses observed, together with our preclinical results, confirm liarozole's dual mechanism of action and provide a rationale for further evaluation of RAMBAs in the treatment of breast cancer.

Perception of quality of life by patients, partners and treating physicians.

The objective of the study was to determine possible differences in perception of quality of life (QoL) between patients with metastatic breast or prostate cancer, their partners, and the treating physician. Patients with metastatic breast cancer (n = 71), and metastatic prostate cancer (n = 29), a partner, and the physician each completed the same QoL questionnaire indicating how they perceived the patient's QoL. The European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire was used to assess patients with breast cancer and the modified prostate cancer specific quality of life instrument (PROSQOLI) for patients with prostate cancer. There was reasonable agreement in mean scores between patients, and physicians or partners, for many domains of QoL; however, there was substantial discordance between scores when considering individual patients. For patients with metastatic breast cancer, physicians systematically underestimated overall QoL (p = 0.0002), social functioning (p = 0.001), and role functioning (p = 0.008), while partners showed better agreement. With prostate cancer physicians tended to underestimate pain, while mean scores for spouses were more concordant. There is substantial variability between ratings of QoL by physicians or partners, as compared to patient ratings. Medical decisions should be based on information about QoL provided by patients using validated methods.

Upper limb work-related musculoskeletal disorders among newspaper employees: cross-sectional survey results.

At a metropolitan newspaper office in Canada with extensive video display terminal (VDT) use, researchers carried out a survey (n = 1,007, 84% response) to establish baseline prevalence of work-related musculoskeletal disorders (WMSDs) and to identify demographic, postural, task, and psychosocial factors associated with WMSD symptoms. One-fifth of the respondents reported moderate or worse upper limb pain recurring at least monthly or lasting more than a week over the previous year. Logistic regression showed that employees who faced frequent deadlines and high psychological demands (fast work pace and conflicting demands), had low skill discretion and social support, spent more time keyboarding, or who had their screen in a non-optimal position were more likely to report moderate to severe symptoms. Women reported significantly higher levels of symptoms than men.