Amplifying the Patient Voice: A Survey of Practitioners' Use of Patient-reported Outcome Measures Across Radiotherapy Providers in England.

AIMS: The NHS England Radiotherapy Service Specification calls for routine use of patient-reported outcome measures (PROMs). However, barriers exist at patient, healthcare professional and service levels. The aim of the present study was to determine the current use of PROMs within radiotherapy services in England. The current attitudes, barriers and enablers to the implementation of PROMs in radiotherapy practice were evaluated and practical recommendations to inform future implementation were developed. MATERIALS AND METHODS: A mixed-methods approach was adopted to obtain quantitative and qualitative data. An online questionnaire was developed and disseminated to all radiotherapy operational delivery network managers across England. The questionnaire consisted of 12 open and closed questions relating to PROMs use, with the option to provide free-text responses. Inductive thematic analysis was conducted on free-text comments, whereas descriptive statistics were used to analyse quantitative data. RESULTS: In total, 182 responses were received from 40 of the 50 radiotherapy providers, resulting in a response rate of 84%. The current use of PROMs was analysed, including rationale for use, tools used, format of PROMs collection and timing within the radiotherapy pathway. Most respondents indicated that PROMs were used in the context of clinical trials only. Through thematic analysis, four identical key themes were identified relating to both barriers and enablers to PROMs use; these included IT infrastructure, time, human/financial resources and training/education. A fifth theme, standardisation, was identified as a key enabler to PROMs use. CONCLUSIONS: Our findings show that outside of clinical trials, PROMs are not routinely used in radiotherapy services due to barriers identified at professional and service levels. Here we provide recommendations to mitigate the barriers identified and implement PROMs in radiotherapy, including training for healthcare professionals and standardisation of PROMs tools and storage. This study provides a key first step in driving PROMs implementation within radiotherapy services across England.

Radiotherapy-specific interprofessional learning through simulation.

INTRODUCTION: Interprofessional learning (IPL) is a vital aspect of training in radiation oncology professions, yet is rarely delivered to those professionals who work most closely together in clinical practice. Scenario-based learning using simulation facilities provides a unique opportunity to facilitate this learning and this project aimed to determine the impact and value of this initiative. METHODS: Small groups comprising post-graduate diploma pre-registration therapeutic radiographers, medical physics trainees and radiation oncology registrars were challenged with 4 plausible and challenging radiotherapy scenarios within an academic simulation centre. Pre- and post-event completion of the "Readiness for Interprofessional Learning Scale" measured impact and a Likert-style survey gathered feedback from participants. RESULTS: The session increased participants' teamwork and collaboration skills as well as strengthening professional identities. Participants reported high levels of enjoyment related to collaborative working, communication and observing other professionals deploying their technical skills and specialist knowledge. CONCLUSION: Although beneficial, simulated scenarios offering equal opportunities for engagement across the professions are challenging to plan and timetabling issues between the 3 groups present significant difficulties. The safe environment and unique opportunity for these groups to learn together was particularly well received and future oncology-specific simulated scenario sessions are planned with larger cohorts. IMPLICATIONS FOR PRACTICE: Simulated scenario training can be used to improve team working across the radiotherapy interprofessional team and may have wider use in other specialist interdisciplinary team development.

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection.

Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3(+) and TUNEL(+) hepatocytes, as well as total, CD4(+), CD8(+), Foxp3(+) and CD20(+) lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3(+) r = 0.74, p < 0.0001; TUNEL(+) r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3(+) cell count was increased in severe hepatitis (p = 0.009). Total, CD4(+), CD8(+) and Foxp3(+) lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8(+) cells correlated with infected (r = 0.495, p 0.04) and TUNEL(+) hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3(+) hepatocytes (r = 0.387, p 0.04). In adults, CD8(+) was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8(+) r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

Image based feasibility of renal sparing surgery for very low risk unilateral Wilms tumors: a report from the Children's Oncology Group.

PURPOSE: Nephrectomy with lymph node sampling is the recommended treatment for children with unilateral Wilms tumor under the Children's Oncology Group protocols. Using radiological assessment, we determined the feasibility of performing partial nephrectomy in a select group of patients with very low risk unilateral Wilms tumor. MATERIALS AND METHODS: We reviewed imaging studies of 60 patients with a mean age of less than 2 years with very low risk unilateral Wilms tumor (mean weight less than 550 gm) to assess the feasibility of partial nephrectomy. We evaluated percentage of salvageable parenchyma, tumor location and anatomical features preventing a nephron sparing approach. RESULTS: A linear relationship exists between tumor weight and computerized tomography estimated tumor volume. Mean tumor weight in the study population was 315 gm. Partial nephrectomy was deemed feasible in only 5 of 60 patients (8%). CONCLUSIONS: When considering a select population with very low risk unilateral Wilms tumor (lower volume tumor), only a small percentage of nonpretreated patients are candidates for nephron sparing surgery.

De novo CDH1 mutation in a family presenting with early-onset diffuse gastric cancer.

In this report, we describe the first concluded case of a de novo germline mutation in CDH1 in a hereditary diffuse gastric cancer (HDGC) kindred. The incident case was a woman with a personal history of Hodgkin's lymphoma and diffuse gastric cancer, who was then confirmed to have a CDH1 mutation (c.1792 C>T (R598X)). The patient's mother was found to have the same CDH1 germline mutation; however, neither maternal grandparent was found to carry the mutation, thus leading to a conclusion that the proband's mother's mutation is of de novo origin. This case highlights the importance of recognition of the HDGC syndrome and of testing for CDH1 germline mutations in young individuals with diffuse gastric cancer without a family history of the disease.

Carcinomatosis peritoneal: resultados quirúrgicos de la cirugía de citorreducción y quimioterapia / Peritoneal carcinomatosis: results of surgical cytoreduction surgery and chemotherapy

Objetivo: Presentar la experiencia preliminar en el tratamiento de la carcinomatosis peritoneal de origen gastrointestinal y ginecológico. Métodos: El estudio incluye 11 pacientes portadores de carcinomatosis, tratados por medio de citorreducción y quimioterapia hipertérmica intraoperatoria y operados entre enero del 2005 y enero del 2008. Resultados: La mediana de edad de los pacientes fue de 50 años (rango = 22-56) y pertenecieron al sexo masculino el 54.5%. La mediana de duración del procedimiento citorreductivo fue de 630 min (rango 205-840). La citorreducción completa fue obtenida en el 54,6% (6/11) de los pacientes. La mediana de órganos resecados por paciente fue 4 (rango = 2 - 5) y la mediana de peritonectomia por paciente fue de 3 (rango = 0-6). Las drogas utilizadas para el baño hipertérmico fueron la Mitomicina C en las carcinomatosis por cancer de colon y del apéndice y el Cisplatino en carcinomatosis por cáncer de ovario. El tiempo d irrigación fue de 90 min y la mediana de la temperatura alcanzada fue de 41º C (39ºC - 43ºC). La mortalidad posoperatoria fue del 9,1% (1/11) y la morbilidad del 63,6% (7/11). La mediana de internación fue de 10 días (4-67), en los pacientes complicados la media de internación fue de 44 días para las severas y de 9 días para las leves. La supervivencia libre de tumor fue del 30% (mediana de seguimiento de 8,3 meses).

The effects of postoperative pain and its management on postoperative cognitive dysfunction.

To determine risks for postoperative cognitive dysfunction (POCD), the authors conducted a prospective cohort study of 225 patients > or = 65 years of age undergoing noncardiac surgery. Cognitive testing using the Word List, Verbal Fluency, and Digit Symbol tests was conducted for each patient preoperatively and 1 and 2 days postoperatively in patients without postoperative delirium. POCD was defined as meeting statistical criteria for decline from the patient's preoperative performance levels on at least two of the three cognitive tests. Multivariate logistic regression analysis determined the association between pain and postoperative analgesia with POCD after controlling for demographics, comorbidities, preoperative level of cognitive and daily functioning, preoperative medications, duration and type of anesthesia, and adverse events. Patients were on average 72 years old and 13% of patients experienced POCD on day 1, 7% on day 2, and 15% had POCD on either day 1 or day 2 after the surgery. Multivariate regression analyses revealed that only postoperative analgesia was associated with the development of POCD. Compared with those receiving postoperative analgesia through a patient-controlled analgesia device that administered opioids intravenously, those who received postoperative analgesia orally were at significantly lower risk for the development of POCD (odds ratio: 0.22; 95% confidence interval: 0.06-0.80; Wald chi-square = 5.36, df = 1, p = 0.02). Older patients undergoing noncardiac surgery who are not delirious can experience significant declines in cognitive functioning postoperatively. Those at least risk of experiencing POCD were those who received postoperative analgesia orally.

Postoperative delirium: the importance of pain and pain management.

Postoperative delirium is common in geriatric patients. Few studies have examined events in the postoperative period that may contribute to the occurrence of postoperative delirium. We hypothesized that postoperative delirium is related to postoperative pain and/or pain management strategy. Patients aged > or =65 years who were scheduled for major noncardiac surgery were studied. A structured interview was conducted preoperatively and for the first 3 postoperative days to determine the presence of delirium using the Confusion Assessment Method. The method of postoperative pain management, as well as pre- and postoperative medications for the first 3 days, was collected. Pre- and postoperative pain at rest and with movement was recorded using the Visual Analog Scale. Three hundred thirty-three patients, with a mean age of 74 +/- 6 years, were studied. After surgery, 46% of patients developed postoperative delirium. By multivariate logistic regression, age (odds ratio [OR], 2.5; 95% confidence interval [CI] 1.5 to 4.2), moderate (OR, 2.2; 95% CI 1.2 to 4.0) and severe (OR, 3.7; 95% CI 1.5 to 9.0) preoperative resting pain, and increase in level of pain from baseline to postoperative day one (OR, 1.1; 95% CI 1.01 to 1.2) were independently associated with a greater risk for the development of postoperative delirium. In contrast, patients who used oral opioid analgesics as their sole means of postoperative pain control were at decreased risk of developing delirium in comparison with those who used opioid analgesics via IV patient-controlled analgesia technique (OR, 0.4; 95% CI 0.2 to 0.7). These results validate our hypothesis that pain and pain management strategies are important factors related to the development of postoperative delirium in elderly patients.

Are preoperative depressive symptoms associated with postoperative delirium in geriatric surgical patients?

BACKGROUND: Delirium is common in older surgical patients and predicts negative health outcomes. Whether depressive symptoms are prevalent and predict the development of postoperative delirium in elderly surgical patients has not been investigated. Our study aimed to examine the prevalence and prognostic importance of preoperative depressive symptoms in older surgical patients. METHODS: Patients at least 65 years of age who were scheduled for major noncardiac surgery were recruited. Preoperatively, patients were screened for symptoms of depression using the 15-point Geriatric Depression Scale (GDS). Postoperative delirium was measured using the Confusion Assessment Method. The associations between covariates and preoperative depression, and postoperative delirium were determined by multivariate logistic regression. RESULTS: In the 219 patients studied, the mean age was 73.6 +/- 6 years, 12% of patients reported six or more depressive symptoms, and 32% reported three to five depressive symptoms. By multivariate logistic regression, patient characteristics associated with six or more symptoms of depression included <12 years of education, moderate to severe limitation in functional status, and drinking more than two alcoholic beverages per day. Postoperatively, 46% of patients developed delirium. Patients with a greater number of preoperative depressive symptoms were more likely to develop postoperative delirium (p =.048) and experience a longer duration of postoperative delirium (p =.027). Even after adjusting for covariates associated with depression and postoperative delirium--including age, educational level, functional status, and preoperative alcohol use--patients with more than six preoperative depressive symptoms were still significantly more likely to have a longer duration of postoperative delirium than did those patients with fewer than two depressive symptoms (odds ratio = 2.69, confidence interval = 1.04-6.93). CONCLUSION: Preoperative screening for the presence of depressive symptoms can be performed easily in elderly patients, and yields useful prognostic information relating to postoperative delirium.

Mutación del gen BMPR1A (Bone Morphogenetic Protein Receptor 1A) en un caso de poliposis juvenil / BMPR1A (Bone Morphogenetic Protein Receptor 1A) gene mutation in juvenile polyposis: a case report

Antecedentes: la poliposis juvenil (PJ) es una infrecuente afección hereditaria autosómica dominante caracterizada por la presencia de múltiples pólipos hamartomatosos gastrointestinales. Hasta el momento se han identificado 3 genes relacionados a esta afección: SMAD4 (cromosoma 18q21), el PTEN (cromosoma 10q23) y recientemente el BMPR1A (cromosoma 10q22-23). El diagnóstico genético permite optimizar el manejo de estos pacientes. Objetivo: presentar los resultados del diagnóstico clínico de poliposis juvenil. Método: paciente de sexo masculino de 16 años de edad con pólipos colónicos cuyas biopsias preoperatorias informaron la presencia de componentes adenomatosos, hamartosos e hiperplásicos. Luego de la resección endoscópica de 6 pólipos rectosigmoideos, se le realizó una colectomía subtotal con ileo-recto anastomosis. Antes de poder contar con el diagnóstico genético y a fin de determinar la posible afectación fenotípica se indicó videocolonoscopías (VFCC) a ambos padres y a cuatro hermanos. Luego del asesoramiento genético se obtuvo el consentimiento informado y se mandaron las muestras de sangre del paciente y sus padres a la Universidad de Iowa, USA para la determinación de mutaciones germinales en los genes SMAD 4 y BMPR1A. Resultados: todas las VFCC efectuadas fueron normales. El estudio molecular encontró una mutación germinal del gen BMPR1A (864-868 del ACTTGIVS7 + 1-2delgt) en el paciente y ausencia de la misma en ambos padres. Se concluyo que se trataba de una mutación "de novo" asociada a la poliposis juvenil y que por lo tanto ninguno de sus familiares presentaba riesgo aumentado. En base a esta información no se recomendó continuar con la vigilancia estricta de los mismos. Conclusión: la identificación de la mutación germinal permitió confirmar el diagnóstico de poliposis juvenil y estimar el riesgo de presentar dicha enfermedad en los familiares cosanguineos optimizando la estrategia de prevención en la familia.

Mutación del gen BMPR1A (Bone Morphogenetic Protein Receptor 1A) en un caso de poliposis juvenil / BMPR1A (Bone Morphogenetic Protein Receptor 1A) gene mutation in juvenile polyposis: a case report

Antecedentes: la poliposis juvenil (PJ) es una infrecuente afección hereditaria autosómica dominante caracterizada por la presencia de múltiples pólipos hamartomatosos gastrointestinales. Hasta el momento se han identificado 3 genes relacionados a esta afección: SMAD4 (cromosoma 18q21), el PTEN (cromosoma 10q23) y recientemente el BMPR1A (cromosoma 10q22-23). El diagnóstico genético permite optimizar el manejo de estos pacientes. Objetivo: presentar los resultados del diagnóstico clínico de poliposis juvenil. Método: paciente de sexo masculino de 16 años de edad con pólipos colónicos cuyas biopsias preoperatorias informaron la presencia de componentes adenomatosos, hamartosos e hiperplásicos. Luego de la resección endoscópica de 6 pólipos rectosigmoideos, se le realizó una colectomía subtotal con ileo-recto anastomosis. Antes de poder contar con el diagnóstico genético y a fin de determinar la posible afectación fenotípica se indicó videocolonoscopías (VFCC) a ambos padres y a cuatro hermanos. Luego del asesoramiento genético se obtuvo el consentimiento informado y se mandaron las muestras de sangre del paciente y sus padres a la Universidad de Iowa, USA para la determinación de mutaciones germinales en los genes SMAD 4 y BMPR1A. Resultados: todas las VFCC efectuadas fueron normales. El estudio molecular encontró una mutación germinal del gen BMPR1A (864-868 del ACTTGIVS7 + 1-2delgt) en el paciente y ausencia de la misma en ambos padres. Se concluyo que se trataba de una mutación "de novo" asociada a la poliposis juvenil y que por lo tanto ninguno de sus familiares presentaba riesgo aumentado. En base a esta información no se recomendó continuar con la vigilancia estricta de los mismos. Conclusión: la identificación de la mutación germinal permitió confirmar el diagnóstico de poliposis juvenil y estimar el riesgo de presentar dicha enfermedad en los familiares cosanguineos optimizando la estrategia de prevención en la familia. (AU)

[Multifocal biliary papillomatosis: an indication for liver transplantation]. / Papillomatose multifocale des voies biliaires: une indication de transplantation hépatique.

Biliary papillomatosis is a uncommon disease. Because of the high rate of recurrence and the possibility of malignant transformation, liver resection or transplantation was recommended. A case of diffuse bilobar biliary papillomatosis, in a 60 years old patient, responsible for cholangitis, cholestasis and for high portal pressure (esophageal varices grade I and II and hypersplenisme) is reported. The patient had had an external biliary drainage leading to an great loss of hydroelectrolytic component important. Opacification and biopsies under endoscopic control assert the right diagnosis. He was treated by a orthotopic liver transplantation. Post operative course was simple. In the 9th month, it was asymptomatic with a completely satisfactory evolution. The other therapeutic modalities was discussed, as well as the review of the literature.

Evaluation of a breast cancer patient information and support program.

CONTEXT: Women with newly diagnosed breast cancer seek answers to many questions about their disease, treatment options, and prognosis. Failure to meet these needs may cause dissatisfaction with the care process. OBJECTIVE: To evaluate the impact of a support and information program for women with newly diagnosed breast cancer. INTERVENTION: A support and information program that featured a program coordinator, information resources, and mentoring from a breast cancer survivor. DESIGN AND OUTCOME MEASURES: Women in whom breast cancer was diagnosed at program sites (n = 111) and a random sample of women whose breast cancer was diagnosed at nonprogram sites (n = 277) were surveyed by mail to ascertain their level of satisfaction with various aspects of their medical care. The response rates were 74% and 81%, respectively. RESULTS: 75% of women at program sites used the information resources, and 60% requested a patient mentor. Demographic characteristics and satisfaction with non-breast cancer care were almost identical among program and non-program site respondents. For overall breast cancer care, 71% of program site respondents but only 56% of non-program site respondents were very satisfied. More than half of program site respondents rated presurgery care, provision of information, and support received as excellent, versus about 40% of non-program site respondents. Program site respondents were consistently more likely to rate the amount of reassurance and support provided by physicians and nurses as excellent and were less likely to want a second opinion (35% vs. 51%). CONCLUSIONS: The support and information program appears to have had a positive impact on satisfaction with breast cancer care.

Low altitude dose measurements from APEX, CRRES and DMSP.

Dosimeter data taken on the APEX (1994-1996), CRRES (1990-1991) and DMSP (1984-1987) satellites have been used to study the low altitude (down to 350 km) radiation environment. Of special concern has been the inner edge of the inner radiation belt due to its steep gradient. We have constructed dose models of the inner edge of the belt from all three spacecraft and put them into a personal computer utility, called APEXRAD, that calculates dose for user-selected orbits. The variation of dose for low altitude, circular orbits is given as a function of altitude, inclination and particle type. Dose-depth curves show that shielding greater than approximately 1/4 in Al is largely ineffectual for low altitude orbits. The contribution of outer zone electrons to low altitude dose is shown to be important only for thin shields and to have significant variation with magnetic activity and solar cycle.

A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin.

We performed a pilot clinical trial with safingol (L-threo-dihydrosphingosine), a protein kinase C-specific inhibitor that potentiates the effect of doxorubicin (DOX) in tumor-bearing animals. Safingol was initially administered as a 1-h infusion at escalating doses. Fourteen days later, patients received the same dose of safingol in combination with a fixed dose of DOX. The combination was repeated at 3-week intervals. Safingol dose levels ranged from 15 to 120 mg/m2. The plasma levels achieved at the final dose level were comparable to those associated with potentiation of DOX in animals. The mean Cmax and area under the curve for safingol at the 120 mg/m2 dose level were 1040 +/- 196 ng/ml and 1251 +/- 317 mg x h/ml, respectively. The mean plasma half-life for safingol was 3.97 +/- 2.51 h, the mean estimated clearance was 3140 +/- 765 ml/min, and the mean volume of distribution was of 995 +/- 421 liters. Coadministration of a fixed dose of DOX did not significantly change the pharmacokinetics of safingol, nor did increasing doses of safingol significantly affect the pharmacokinetics of DOX. Minor responses were observed in three patients with pancreatic cancer and one patient with angiosarcoma of the scalp. This pilot Phase I study indicates that the protein kinase C inhibitor safingol can be given safely with 45 mg/m2 of DOX at a dose that is potentially pharmacologically active without dose-limiting toxicity.

Salvage radiotherapy for local failures of lumpectomy and breast irradiation.

BACKGROUND AND PURPOSE: In-breast tumor recurrence (IBTR) following lumpectomy and breast irradiation is usually managed by mastectomy. For women who refused mastectomy at the time of an IBTR, a repeat course of radiotherapy following repeat lumpectomy was offered. MATERIALS AND METHODS: Sixteen women with an IBTR following lumpectomy, axillary node dissection and breast irradiation were treated with repeat lumpectomy and radiotherapy to the operative area. Fifteen patients received 5000 cGy/25 fractions. One patient discontinued radiotherapy for non-medical reasons after having received only 3200 cGy/16 fractions. The interval from completion of the initial course of radiotherapy to documentation of IBTR varied from 10-130 months (median 31 months). RESULTS: Four patients (20%) have had further local failure. Ten of sixteen patients (62.5%) are alive and free or disease at 42-119 months from completion of the repeat course of radiotherapy. Of these latter patients, one had another in-breast tumor recurrence treated by excision alone and another had an in-breast tumor recurrence in the contra lateral breast post-lumpectomy and irradiation. Four patients died with distant metastasis, one is currently alive with contralateral breast cancer and distant metastasis, and one is alive with an extensive recurrence in the re-irradiated breast. Two of the patients with distant metastasis had abnormal bone scans at the time they received the repeat course of radiotherapy. There have been no severe late sequelae from the repeat course of radiotherapy. CONCLUSIONS: For selected patients, a repeat course of radiotherapy for an IBTR following lumpectomy and radiotherapy is well tolerated and may provide long-term local control.