The utility of publicly reported cancer treatment wait time information for patients and health care providers.

AIMS: To determine the utility of web-based radiation wait time information for patients and health care providers in decision-making. To revise the information using a simulated laboratory environment and to re-evaluate the new web-based information. MATERIALS AND METHODS: An online 'pop-up' survey on the Cancer Care Ontario (CCO) website measured user satisfaction. Qualitative data were gathered through patient focus groups and physician interviews. On the basis of the analysis, the website was revised and usability testing conducted. The information was re-evaluated by end-users through survey methodology. RESULTS: The majority accessing the wait time website were patients and family members. The modal age of use of the website was 31-50 years. Patients found the information more helpful after redesign than health professionals, but both found the language less easy to understand, highlighting the need to continuously evaluate the effectiveness of the website. Patients did not identify themselves as consumers of wait time information. Their expectation was that physicians would determine the urgency for treatment and would ensure timely access to care. Physicians reported that they did not use the CCO website on wait times and would not use the data for decision-making. Referrals were based on urgency of care and usual referral patterns. Referral patterns did not shift to centres with shorter wait times. CONCLUSIONS: The results of this study did not confirm the usefulness of the web-based wait time information for patients and physicians as a resource on how to obtain timely access to radiation treatment. Patients relied on their physician to manage their access to treatment according to the urgency of their clinical condition. Physicians preferred their established referral process rather than referring their patients to centres with shorter wait times. As patients become more computer savvy, it will be interesting to see if they increasingly become consumers of web-based wait time information.

Organisational standards for the delivery of intensity-modulated radiation therapy in Ontario.

By minimising the effect of irradiation on surrounding tissue, intensity-modulated radiation therapy (IMRT) can deliver higher, more effective doses to the targeted tumour site, minimising treatment-related morbidity and possibly improving cancer control and cure. A multidisciplinary IMRT Expert Panel was convened to develop the organisational standards for the delivery of IMRT. The systematic literature search used MEDLINE, EMBASE, the Cochrane Database, the National Guidelines Clearing House and the Health Technology Assessment Database. An environmental scan of unpublished literature used the Google search engine to review the websites of key organisations, cancer agencies/centres and vendor sites in Canada, the USA, Australia and Europe. In total, 22 relevant guidance documents were identified; 12 from the published literature and 10 from the environmental scan. Professional and organisational standards for the provision of IMRT were developed through the analysis of this evidence and the consensus opinion of the IMRT Expert Panel. The resulting standards address the following domains: planning of new IMRT programmes, practice setting requirements, tools, devices and equipment requirements; professional training requirements; role of personnel; and requirements for quality assurance and safety. Here the IMRT Expert Panel offers organisational and professional standards for the delivery of IMRT, with the intent of promoting innovation, improving access and enhancing patient care.

PPARgamma activators down-regulate the expression of PPARgamma in 3T3-L1 adipocytes.

Transcriptional activation of PPARgamma by the anti-diabetic compound troglitazone enhances the rate of 3T3-L1 adipocyte differentiation. In this study, we examined the effects of troglitazone, a specific PPARgamma ligand, on the expression of PPARgamma during and after 3T3-L1 adipocyte differentiation. Troglitazone treatment caused a significant decrease in PPARgamma proteins and DNA binding activity. This reduction was associated with a similar decrease in transcription of PPARgamma mRNA. These data suggest that in 3T3-L1 cells, the expression of PPARgamma is auto-regulated.

Anti-MAG antibodies: major effects of antigen purity and antibody cross-reactivity on ELISA results and clinical correlation.

There is controversy regarding the relationship of polyneuropathy syndromes to the presence of serum antibody binding to myelin-associated glycoprotein (MAG). Using standard ELISA methodology, we identified 74 sera that appeared to have high titers of IgM binding to MAG and found that only 34% of these sera stained MAG using Western blot methodology. Follow-up studies showed that two factors greatly influence concordance between ELISA and Western blot testing for anti-MAG antibodies. Sera with high titers of binding to both MAG and histone H3 identified by ELISA rarely stain MAG on Western blot. In addition, sera analyzed by ELISA often bind to impurities in the semipure MAG that is frequently used in ELISA assays. Further purifications to separate MAG from other contaminants improved concordance between ELISA and Western blot results to 85% to 90% in a retrospective analysis, as well as in a prospective study of 49 additional sera. Patients with a polyneuropathy and serum IgM binding to MAG preparations by ELISA but not by Western blot methodology had several different clinical syndromes, including gait disorders and asymmetric motor neuropathies. Patients with IgM binding to MAG by both assay methods usually had a distal, sensory-motor, symmetric polyneuropathy with some features of demyelination on electrodiagnostic testing.

Health-related quality of life in survivors of tumours of the central nervous system in childhood--a preference-based approach to measurement in a cross-sectional study.

There is an evident need to measure the comprehensive burden of morbidity experienced by survivors of brain tumours in childhood. To this end, a questionnaire based on the Health Utilities Index mark 2 (HUI2) and mark 3 (HUI3) systems was completed independently for a cohort of such children by their parents, by a nurse, by physicians and by a selected group of the children themselves. Each of the HUI2 and HUI3 systems consists of a multi-attribute health status classification scheme linked to a preference function which provides utility scores for levels within single attributes (domains of health) and for global health states. All eligible families (n = 44) participated. Even cognitively impaired children of at least 9.5 years of age could complete the questionnaire. The greatest burden of morbidity, occurring in two-thirds of children, was in the attribute of cognition. Surprisingly, almost one-third of children experienced pain. Global health status was lowest in children who underwent radiotherapy before the age of 5 years and the corresponding utility scores were related inversely to the volume irradiated. Children with demonstrable disease had lower scores than those in whom disease was not evident. There was a high level of agreement (intraclass correlation coefficients > 0.5) on formal assessment of inter-rater reliability for global health-related quality of life utility scores. The usefulness of measures of health status and health-related quality of life, in children surviving brain tumours, has been demonstrated by this study.

Osteopenia in children surviving brain tumours.

Osteopenia has been reported in children surviving acute lymphoblastic leukaemia, apparently as a consequence of therapy. It has been suggested that cranial irradiation may play a crucial role in this disorder. To explore that possibility, survivors of brain tumours in childhood, all of whom had received radiotherapy, were examined for evidence of bone mineral loss. 19 children were assessed, on average at 7 years after treatment. Measurements of growth velocities, plain radiography of the skeleton, bone densitometry, health-related quality of life and physical activity were undertaken. Growth hormone (GH) deficiency had been detected in 6 children and 5 had received GH replacement, for a minimum of more than 3 years. 9 children were radiographically osteopenic (including the 5 who had received GH). Z scores for bone mineral density (BMD) were negative in the majority of children. Health-related quality of life was less and pain more frequent in those with low BMD scores. Pain was correlated negatively with both free-time activity and seasonal activity (P < 0.01). Osteopenia is a common sequel of therapy in children with brain tumours. Those with osteopenia have more pain and more compromised, health-related quality of life than those who are not osteopenic, and pain significantly limits physical activity. The pathogenesis of osteopenia in these children is still uncertain, but is likely to be multifactorial.

Low grade glioma of the cerebral hemispheres in adults: a retrospective analysis of 88 cases.

Eighty-eight adult patients with histologically verified cerebral low grade gliomas (grades 1 and 2) treated with post-operative radiotherapy at the Royal Marsden Hospital between 1960 and 1985 were reviewed. Survival of oligodendroglioma patients was greater than those with astrocytoma (64% vs 36% at 5 years) but the difference was less marked in the long term (35% vs 26% at 10 years). Previous studies have identified prognostic factors important in these tumors: age, extent of surgery, grade, performance status, and duration of symptoms. In this study of low grade astrocytomas and oligodendrogliomas, age (highly significant in the former and significant in the latter), extent of surgery (oligodendrogliomas), and performance status have been demonstrated as factors influencing outcome. The precise role of radiotherapy including the optimal radiation dose and timing of treatment remains unclear. The information, given by a retrospective analysis such as this, helps in the design of prospective, randomized studies looking at radiation dose and time of surgical and radiotherapeutic interventions, always with careful assessment needed of quality of life and treatment morbidity.

Combining backscattered electrons and low energy photons to improve the dose distribution to an eyelid.

In electron beam therapy, backscattered electrons from metal shields result in a high dose to tissue in the vicinity of the shield. Data are now available which enable both the magnitude of the dose enhancement at the interface and the fall off in dose 'up stream' to be determined. With the aid of these data, a combined modality therapy (5 MeV electrons, 1.1 mm A1 HVL X rays) was given to an eyelid during which the lens was protected with a superficial X ray lead eye shield. The eyelid was treated to a mid lid dose of 45 Gy in 28 days, and the dose gradient on the beam central axis was more uniform (+/- 3%) than that obtainable with superficial X rays alone. The lens dose from the combined therapy was estimated to be less than 0.25 Gy.

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.

PURPOSE: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. METHODS AND MATERIALS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. RESULTS: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm. CONCLUSION: Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.

Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the Radiation Therapy Oncology Group protocol 91-04.

PURPOSE: Little information is available on the importance of pretreatment Mini-Mental Status Exam (MMSE) on long-term survival and neurologic function following treatment for unresectable brain metastases. This study examines the importance of the MMSE in predicting outcome in a group of patients treated with an accelerated fractionation regimen of 30 Gy in 10 daily fractions in 2 weeks. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastases were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. Two hundred twenty-four patients were entered on the accelerated fractionated arm, and 182 were eligible for analysis (7 patients were judged ineligible, no MMSE information in 29, no survival data in 1, no forms submitted in 1). RESULTS: Average age was 60 years; 58% were male and 25% had a single intracranial lesion on their pretherapy evaluation. KPS was 70 in 32%, 80 in 31%, 90 in 29%, and 100 in 14%. The average MMSE was 26.5, which is the lower quartile for normal in the U.S. population. The range of the MMSE scores was 11-30 with 30 being the maximum. A score of less than 23 indicates possible dementia, which occurred in 16% of the patients prior to treatment. The median time from diagnosis to treatment was 5 days (range, 0-158 days). The median survival was 4.2 months with a 95% confidence interval of 3.7-5.1 months. Thirty-seven percent of the patients were alive at 6 months, and 17% were alive at 1 year. The following variables were examined in a Cox proportional-hazards model to determine their prognostic value for overall survival: age, gender, KPS, baseline MMSE, time until MMSE below 23, time since diagnosis, number of brain metastases, and radiosurgery eligibility. In all Cox model analyses, age, KPS, baseline MMSE, time until MMSE below 23, and time since diagnosis were treated as continuous variables. Statistically significant factors for survival were pretreatment MMSE (p = 0.0002), and KPS (p = 0.02). Age was of borderline significance (p = 0.065) as well as gender (p = 0.074). A poorer outcome is associated with an increasing age, male gender, lower MMSE, and shorter time until MMSE below 23. Improvement in MMSE over time was assessed; 62 patients died prior to obtaining follow-up MMSE, and 30 patients had a baseline MMSE of 30 (the maximum), and, therefore, no improvement could be expected. Of the remaining 88, 48 (54.5%) demonstrated an improvement in their MMSE at any follow-up visit. Lack of decline of MMSE below 23 was seen in long-term survivors, with 81% at 6 months and 66% at 1 year of patients maintaining a MMSE above 23. Analysis of time until death from brain metastases demonstrated that decreasing baseline MMSE (p = 0.003) and primary site (breast vs. lung vs. other p = 0.032) were highly associated with a terminal event. CONCLUSION: While gender and perhaps age remain significant predictors for survival, MMSE is also an important way of assessing a patient's outcome. Accelerated fractionation used in the treatment of brain metastases (30 Gy in 10 fractions) appears to also be associated with an improvement in MMSE and a lack of decline of MMSE below 23 in long-term survivors.

Accelerated radiation therapy for primary lymphoma of the brain.

BACKGROUND AND PURPOSE: We report the results of a pilot study of the use of accelerated radiation therapy for 10 patients with primary lymphoma of the brain. MATERIALS AND METHODS: There were five females and five males with a median age of 60 years (range 31-77 years) and a median Karnofsky performance status of 60 (range 30-90). Nine patients underwent biopsies only and one patient underwent a partial resection. The radiation therapy consisted of 50 Gy in 25 fractions over 13 consecutive days to the whole brain including all meningeal surfaces. Two fractions were delivered daily with a minimum interval of 6 h between fractions. Treatment was delivered daily right through the weekend with no treatment interruptions. RESULTS: To date nine patients have died. The median survival was 17 months. Seven patients have demonstrated definite evidence of recurrence (six in the brain and one with positive CSF cytology only). There have been two autopsies, one of which demonstrated diffusely recurrent tumor and the other showing residual disease and radiation demyelination and small areas of necrosis in the pons which undoubtedly was the cause of death at 5 months. One patient alive and free of recurrence at 69 months has bilateral radiation retinopathy and an undiagnosed degenerative neurologic condition. CONCLUSION: We conclude that this accelerated schedule of radiation therapy is ineffective in improving survival in primary lymphoma of the brain and is associated with unacceptable increased toxicity.

Attitudes toward motherhood in postnatal depression: development of the Maternal Attitudes Questionnaire.

This article describes the development of the Maternal Attitudes Questionnaire (MAQ), a 14-item self-report instrument measuring cognitions relating to role change, expectations of motherhood, and expectations of the self as a mother in postnatal women. This questionnaire was found to have good test-retest and internal reliability. In a large sample of women (n = 483) at 6-8 weeks postpartum, scores on the questionnaire were highly correlated with scores on the Edinburgh Postnatal Depression Scale (EPDS) and the Revised Clinical Interview Schedule (CIS-R). Cluster analysis demonstrated that, among depressed women with similar symptom scores on the CIS-R, the MAQ discriminated a group with low MAQ scores and a group with high MAQ scores. This finding supports the hypothesis that women who are depressed postnatally are cognitively heterogeneous; such differences may be important in understanding the etiology and determining the treatment of postnatal depression.

The pathway to care in post-natal depression: women's attitudes to post-natal depression and its treatment.

Women suffering from post-natal depression were interviewed about their symptoms, help-seeking behaviour and treatment. Over 90% recognized there was something wrong, but only one-third believed they were suffering from post-natal depression. Over 80% had not reported their symptoms to any health professional.

Phase I study of hyperfractionated whole brain irradiation (HWBI) in the treatment of primary cerebral lymphoma.

The poor prognosis for primary cerebral lymphoma following conventional radiation therapy has generally been attributed to high local relapse rates despite initial local control. Hyperfractionated radiation therapy may improve the therapeutic ratio by allowing higher total radiation doses to be prescribed without exceeding the radiation tolerance of the central nervous system (CNS). Eight patients entered a study of hyperfractionated whole brain irradiation (HWBI) between October 1988 and May 1991. The prescribed dose was 64.8 Gy in 54 fractions over 5.5 weeks. All patients were followed clinically and with computed tomographic scanning. Additional investigations to discriminate between lymphoma recurrence and radionecrosis included magnetic resonance imaging (MRI), thallium-201 single photon emission computed tomography (SPECT), and immunocytological examination of the cerebrospinal fluid (CSF). A complete remission as seen on CT scan was achieved in all cases. The overall median survival was 102 weeks. Six patients initially deteriorated neurologically without evidence of tumour recurrence. Three patients have died without evidence of recurrence at 18, 62 and 128 weeks. As of 31 May 1992, three patients remain alive, two with radiation brain injury at 147 and 184 weeks. Treatment toxicity prompted study closure in September 1991. The hyperfractionation regimen used is reported by others to be free from significant morbidity. The pathogenesis of cerebral lymphomas (diffuse disease, angiotropism, subependymal involvement) may adversely affect CNS radiation tolerance.

The effect of storage conditions on amniotic fluid phosphatidylglycerol concentration.

In certain high-risk gestations, phosphatidylglycerol in the amniotic fluid is reported to be useful in predicting respiratory distress syndrome of the neonate in high-risk patients. This study of amniotic fluid phosphatidylglycerol was performed to determine the degradation of phosphatidylglycerol in both the supernatant and the lamellar bodies of amniotic fluid samples collected from normal term pregnant patients. The objective of the study was to discover whether phosphatidylglycerol retained its stability when measured in transported and stored amniotic fluid. The results of the study showed that phosphatidylglycerol remained stable in all amniotic fluid samples stored at various temperatures over a 3-week period.

Radiotherapy for jugulo-tympanic paragangliomas (glomus jugulare tumours).

Sixty patients with glomus jugulare tumour, seen at St. Bartholomew's Hospital, London, over forty years, have been reviewed. The term 'jugulo-tympanic paraganglioma' is suggested as a more accurate name for these tumours. The following simple classification is recommended: Group I tumours (tympanic paragangliomas) are those with or without VIIth nerve palsy, but with no other cranial nerve involvement. Group II tumours (jugular paragangliomas) are those with involvement of any cranial nerve other than the VIIth. The method and results of treatment by radiotherapy are discussed. It is concluded that surgery and radiotherapy give comparable results in Group I tumours, but radiotherapy gives superior results in Group II tumours.

A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression.

OBJECTIVE: To study the effectiveness of fluoxetine and cognitive-behavioural counselling in depressive illness in postnatal women: to compare fluoxetine and placebo, six sessions and one session of counselling, and combinations of drugs and counselling. DESIGN: Randomised, controlled treatment trial, double blind in relation to drug treatment, with four treatment cells: fluoxetine or placebo plus one or six sessions of counselling. SUBJECTS: 87 women satisfying criteria for depressive illness 6-8 weeks after childbirth, 61 (70%) of whom completed 12 weeks of treatment. SETTING: Community based study in south Manchester. MAIN OUTCOME MEASURES: Psychiatric morbidity after 1, 4, and 12 weeks, measured as mean scores and 95% confidence limits on the revised clinical interview schedule, the Edinburgh postnatal depression scale and the Hamilton depression scale. RESULTS: Highly significant improvement was seen in all four treatment groups. The improvement in subjects receiving fluoxetine was significantly greater than in those receiving placebo. The improvement after six sessions of counselling was significantly greater than after a single session. Interaction between counselling and fluoxetine was not statistically significant. These differences were evident after one week, and improvement in all groups was complete after four weeks. CONCLUSIONS: Both fluoxetine and cognitive-behavioural counselling given as a course of therapy are effective treatments for non-psychotic depression in postnatal women. After an initial session of counselling, additional benefit results from either fluoxetine or further counselling but there seems to be no advantage in receiving both. The choice of treatment may therefore be made by the women themselves.

OS093. Prevalance of sleep disordered breathing in pregnancy.

INTRODUCTION: Snoring is a common symptom of Sleep Disordered Breathing (SDB), a condition that is present in 4% of the general population. SDB is identified by snoring and repetitive cessation of breathing during sleep accompanied by repetitive hypoxia and has been found to be associated with hypertension, stroke and heart attack.The general risk factors associated with severe preeclampsia significantly overlap with those reported to increase the risk of SDB syndromes. Further risk factors that need consideration include: multiple pregnancy, diabetes and chronic hypertension treatment. OBJECTIVES: To determine the prevalence of SDB in the pregnant population in a metropolitan hospital and to examine self-reported snoring against actual snoring as determined by Sonomat © studies and report fetal outcomes of those who snored compared to those who did not snore. METHODS: A questionnaire containing The Epworth Sleepiness Scale and the Berlin Questionnaire (which examines snoring and tiredness) was administered to 3000 pregnancies over a period of two years. Women were additionally recruited for detailed sleep studies, which entailed continuous night time blood pressure monitoring, encephalogram for sleep staging and continuous night time cardiotocographic monitoring. RESULTS: To date, 2206 surveys have been completed. Sleep studies have been undertaken by 280 women, of which half have continuous blood pressure readings. The detailed data provided through these studies is currently being examined and will be completed by June 2012. CONCLUSION: This study is unique and unprecedented in the scope of detailed data obtained through the variety of parameters measured. Coupled with pregnancy progression and comprehensive maternal and neonatal outcomes, it is anticipated that this multi-faceted study will provide a wealth of knowledge on sleep patterns, SDB and its effect on pregnancy for both the mother and the fetus.

PP154. Relationship between recorded and reported snoring during pregnancy: Objective measurement versus questionnaire responses.

INTRODUCTION: Snoring is a common symptom of sleep disordered breathing (SDB), a condition that is present in 4% of the general population. SDB is identified by snoring and repetitive cessation of breathing during sleep accompanied by repetitive hypoxia and has been found to be associated with hypertension, stroke and heart attack. There is not depth of knowledge examining the association between SDB and pregnancy outcomes. OBJECTIVES: To examine the prevalence of self reported snoring in pregnancy and the potential association between self reported snoring and the development of Hypertensive Disorders of Pregnancy (HDP) within a larger cohort from a prevalence of SDB in pregnancy study. METHODS: Questionnaires were administered to pregnant women attending an outpatient's antenatal clinic. The self reported snoring is a component of the Epworth scale. Pregnancy progression and outcome data were collected on all participants and analyse by IBM SPSS v.20™ utilising Chi-square analysis, Student T test and logistic regression analysis. HDP diagnoses were in alignment with the SOMANZ (2009) diagnostic criteria. RESULTS: Questionnaires were administered and outcomes collected on 2023 pregnancies. Snoring was reported by 49.2% of women. HDP affected 10.1% of the cohort, 3.3% of whom were preeclamptic. Of the pregnancies affected by HDP self reported snoring occurred in 57.7% in comparison to 43.3% who do not report snoring (p<0.001). CONCLUSION: This would indicate that there is an association between self reported snoring and the development of HDP. Further analysis will be undertaken to model the effect of other potential risk factors such as maternal age, parity, pre-pregnancy BMI and other co morbidities.