Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program.

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

Patient reported outcomes for quality of life (QOL) by Expanded Prostate Cancer Index (EPIC) on average 15 years post treatment.

Objective/purpose: Previously patient reported quality of life (QOL) was reported in men with prostate cancer a mean 2 and 6 years post treatment with open radical prostatectomy (RP), 3D conformal radiation therapy (3D CRT), or 125I low dose rate (LDR) brachytherapy (BT). Herein we update the results 15 years post-treatment QOL. Materials/methods: The Expanded Prostate Cancer Index (EPIC) domains were scored with differences evaluated at a median 15.8 years follow up based upon mean EPIC summary domains by ANOVA with pairwise post-hoc comparisons adjusted for age. Patient differences of current survey from first cross-section are reported as median change in summary score for each treatment group at median of 2.2 and 6.0, and 15.8 years. Results: Among men still alive response rate was 52% in BT, 60% in 3D CRT, and 62% in RP resulting in 30, 41, and 330 QOL questionnaires to evaluate for each corresponding modality at median follow up of 15.8 years. Men were a mean 75.3, 83.6, and 79.3 years of age after RP, 3DCRT, and BT, respectively.At a median of 15.8 years, there were largely persistent differences in EPIC domains without substantial evolution in QoL from middle time points. Persistent worsening in urinary irritative and bowel domain with 3DRT or BT compared to RP. Trend towards worse urinary incontinence with RP were noted without statistical differences within radiotherapy options. Conclusion: As the EPIC patient reported outcomes with the longest follow-up, these data uniquely reveal temporal trends from 2 to 15 years post treatment. However, the treatment modalities of open RP, 3D CRT without image guidance or intensity modulation, and BT without peripheral loading or MRI guidance may not reflect modern techniques.

European principles of care for physiotherapy provision for persons with inherited bleeding disorders: Perspectives of physiotherapists and patients.

INTRODUCTION: In their Chronic Care Model, the World Health Organisation states that people with chronic disorders and their families should be informed about the expected course, potential complications, and effective strategies to prevent complications and manage symptoms. Physiotherapists are a key professional group involved in the triage, assessment and management of musculoskeletal conditions of persons with a bleeding disorder (PWBD). Nevertheless, recent reports describe access to physiotherapy for those with these conditions is only sometimes available. AIM: Access to high quality individualised physiotherapy should be ensured for all PWBD, including those with mild and moderate severities, male and female, people with von Willebrand Disease (vWD) and other rare bleeding disorders. Physiotherapy should be viewed as a basic requisite in their multidisciplinary care. METHODS/ RESULTS: Following a series of meetings with physiotherapists representing the European Association for Haemophilia and Allied Disorders (EAHAD) and PWBD representing the European Haemophilia Consortium (EHC) and a review of publications in the field, eight core principles of physiotherapy care for persons with a bleeding disorder have been co-produced by EAHAD and EHC. CONCLUSION: These eight principles outline optimum standards of practice in order to advocate personalised patient-centred care for physical health in which both prevention and interventions include shared decision making, and supported self-management.

How does a lifetime of painful experiences influence sensations and beliefs about pain in adults with severe haemophilia? A qualitative study.

PURPOSE: To explore the life experiences of pain in people with severe haemophilia and understand how such experiences influence beliefs and sensation of pain in adulthood. METHODS: A qualitative inquiry approach using focus groups and semi-structured individual interviews was used. Participants included people with severe haemophilia living with chronic pain. Data were analysed using reflexive thematic analysis. RESULTS: Fourteen men with a median age of 47 (range 23-73) agreed to take part. Eleven participated in two focus groups and three were interviewed over telephone. Two themes were conceptualised from the data: (i) haemophilia and pain - an evolving life biography (the personal narrative, historical, social, and medical context, continuous adaptation of activity choices, surveillance of pain and its meaning); (ii) "My normal isn't normal" - identity and self-agency (pain as a feature of life and identify with severe haemophilia, loss of enjoyable activities balanced against staying active, barriers to participation). CONCLUSIONS: Pain is a constantly evolving, lifetime feature for many adults with haemophilia and it is viewed as part of their identity with their condition. Healthcare professionals working in haemophilia should try to better understand the influence of an individuals lived experience with their haemophilia on beliefs and behaviours of pain.Implications for rehabilitationSevere haemophilia is a rare bleeding disorder that results in musculoskeletal joint disease.Adults with severe haemophilia have experienced multiple episodes of bleeding related musculoskeletal pain since childhood.Pain beliefs and behaviours in adulthood appear to be influenced by a lifetime of painful experiences associated with haemophilia.In order to better support people with haemophilia and chronic pain, healthcare professionals in haemophilia need to better understand how an individuals lived experience of pain helps inform their beliefs about it.

The experiences and beliefs of people with severe haemophilia and healthcare professionals on pain management, and their views of using exercise as an aspect of intervention: a qualitative study.

PURPOSE: To explore the experiences, views and beliefs of people with severe haemophilia and healthcare professionals (HCPs) on approaches for pain management, as well as their views on exercise being used as an aspect of management. METHODS: Taking a qualitative inquiry approach using focus groups and semi-structured interviews, participants included people with severe haemophilia living with chronic pain and haemophilia HCPs. Data were analysed using reflexive thematic analysis. RESULTS: Fourteen men with haemophilia with a median age of 47 (range 23-73) and six haemophilia HCPs agreed to participate. Of the people with haemophilia, 11 attended two focus groups and three were interviewed over telephone. Healthcare professionals were interviewed face-to-face. Two themes were conceptualised from the data: (i) haemophilia management and pain management is discordant (imbalance between good haemophilia care but poor pain management, historical medico-social influences on pain management, the need for trust); (ii) uncertain about exercise but clear on what matters (conflicting views on exercise, the need for proof of safety, personalised care). CONCLUSIONS: Options for effective pain management remain limited and what is used is heavily influenced by beliefs and experience. Exercise as a treatment option in pain management is conceptually acceptable for people with haemophilia. Effective pain management requires understanding of individual beliefs and fears, and a personalised approach supported by knowledgeable, trusted clinicians.Implications for rehabilitationMusculoskeletal joint pain and its relationship with bleeding in people with haemophilia continues to be a management challenge.Current pain management strategies are of limited effectiveness with little evidence of an approach that reflects the multi-modal pain experience.Whilst exercise and rehabilitation approaches are conceptually possible for people with severe haemophilia, barriers remain regarding perception of overall safety and effectiveness.People with severe haemophilia may consider exercise as part of a pain management strategy if it is individualised, and they are supported to do it by clinicians who understand them and their haemophilia.

Retrospective study of first episode psychosis in the Dublin Southwest Mental Health Service: demographics, clinical profile and service evaluation of treatment.

OBJECTIVE: In Ireland, National Clinical Programmes are being established to improve and standardise patient care throughout the Health Service Executive. In line with internationally recognised guidelines on the treatment of first episode psychosis the Early Intervention in Psychosis (EIP) programme is being drafted with a view to implementation by mental health services across the country. We undertook a review of patients presenting with a first episode of psychosis to the Dublin Southwest Mental Health Service before the implementation of the EIP. This baseline information will be used to measure the efficacy of our EIP programme. METHODS: Patients who presented with a first episode psychosis were retrospectively identified through case note reviews and consultation with treating teams. We gathered demographic and clinical information from patients as well as data on treatment provision over a 2-year period from the time of first presentation. Data included age at first presentation, duration of untreated psychosis, diagnosis, referral source, antipsychotic prescribing rates and dosing, rates of provision of psychological interventions and standards of physical healthcare monitoring. Outcome measures with regards to rates of admission over a 2-year period following initial presentation were also recorded. RESULTS: In total, 66 cases were identified. The majority were male, single, unemployed and living with their family or spouse. The mean age at first presentation was 31 years with a mean duration of untreated psychosis of 17 months. Just under one-third were diagnosed with schizophrenia. Approximately half of the patients had no contact with a health service before presentation. The majority of patients presented through the emergency department. Two-thirds of all patients had a hospital admission within 2 years of presentation and almost one quarter of patients had an involuntary admission. The majority of patients were prescribed antipsychotic doses within recommended British National Formulary guidelines. Most patients received individual support through their keyworker and family intervention was provided in the majority of cases. Only a small number received formal Cognitive-Behavioural Therapy. Physical healthcare monitoring was insufficiently recorded in the majority of patients. CONCLUSIONS: There is a shortage of information on the profile and treatment of patients presenting with a first episode of psychosis in Ireland. This baseline information is important in evaluating the efficacy of any new programme for this patient group. Many aspects of good practice were identified within the service in particular with regards to the appropriate prescribing of antipsychotic medication and the rates of family intervention. Deficiencies remain however in the monitoring of physical health and the provision of formal psychological interventions to patients. With the implementation of an EIP programme it is hoped that service provision would improve nationwide and to internationally recognised standards.

Recommendations on multidisciplinary management of elective surgery in people with haemophilia.

Planning and undertaking elective surgery in people with haemophilia (PWH) is most effective with the involvement of a specialist and experienced multidisciplinary team (MDT) at a haemophilia treatment centre. However, despite extensive best practice guidelines for surgery in PWH, there may exist a gap between guidelines and practical application. For this consensus review, an expert multidisciplinary panel comprising surgeons, haematologists, nurses, physiotherapists and a dental expert was assembled to develop practical approaches to implement the principles of multidisciplinary management of elective surgery for PWH. Careful preoperative planning is paramount for successful elective surgery, including dental examinations, physical assessment and prehabilitation, laboratory testing and the development of haemostasis and pain management plans. A coordinator may be appointed from the MDT to ensure that critical tasks are performed and milestones met to enable surgery to proceed. At all stages, the patient and their parent/caregiver, where appropriate, should be consulted to ensure that their expectations and functional goals are realistic and can be achieved. The planning phase should ensure that surgery proceeds without incident, but the surgical team should be ready to handle unanticipated events. Similarly, the broader MDT must be made aware of events in surgery that may require postoperative plans to be changed. Postoperative rehabilitation should begin soon after surgery, with attention paid to management of haemostasis and pain. Surgery in patients with inhibitors requires even more careful preparation and should only be undertaken by an MDT experienced in this area, at a specialized haemophilia treatment centre with a comprehensive care model.

Study of physical function in adolescents with haemophilia: The SO-FIT study.

INTRODUCTION: Contemporary haemophilia care demands Patient-Reported Outcomes. SO-FIT is a UK multi-centre study, assessing self-reported function, health-related quality of life (HRQoL) and joint health in boys with severe haemophilia. METHODS: Subjective physical function (PedHAL, HEP-Test-Q) and HRQoL (Haemo-QoL Short Form [SF]) were assessed alongside joint health using the objective Haemophilia Joint Health Score (HJHS v2.1). Demographic and clinical data were collected. RESULTS: Data from 127 boys mean age 12.38 ± 2.5 (range 8-17) treated at 16 sites were analysed. One-hundred-and-thirteen had haemophilia A, 25/9 past/current inhibitor, 124 were treated prophylactically (46.8% primary) and three on-demand. In the preceding 6 months, boys reported median 0 joint bleeds (range 0-8) with a median HJHS score of 1 (range 0-30). Boys reported good physical functioning; HEP-Test-Q (M = 80.32 ± 16.1) showed the highest impairments in the domain "endurance" (72.53 ± 19.1), in PedHAL (M = 85.44 ± 18.9) highest impairments were in the domains "leisure activities & sports" (M = 82.43 ± 23.4) and "lying/sitting/kneeling/standing" (M = 83.22 ± 20.3). Boys reported generally good HRQoL in Haemo-QoL SF SF (M = 22.81 ± 15.0) with highest impairments in the domains "friends" (M = 28.81 ± 30.5) and "sports & school" (M = 26.14 ± 25.1). HJHS revealed low correlations with the Haemo-QoL SF (r = .251, P < .006), the PedHAL (r = -.397, P < .0001) and the HEP-Test-Q (r = -.323, P < .0001). A moderate correlation was seen between HEP-Test-Q and Haemo-QoL SF of r = -.575 (P < .0001) and between PedHAL and Haemo-QoL SFr = -.561 (P < .0001) implying that good perceived physical function is related to good HRQoL. CONCLUSIONS: The SO-FIT study has demonstrated that children with severe haemophilia in the UK report good HRQoL and have good joint health as reflected in low HJHS scores.

Prostate magnetic resonance imaging for brachytherapists: Diagnosis, imaging pitfalls, and post-therapy assessment.

Optimal integration of multiparametric MRI (mp MRI) into prostate brachytherapy practice necessitates an understanding of imaging findings pertinent to prostate cancer detection and staging. This review will summarize prostate cancer imaging findings and tumor staging on mp MRI, including an overview of the Prostate Imaging Reporting and Data System (PIRADS)-structured reporting schema, mp MRI findings observed in the post-therapy setting including cases of post-treatment recurrence, and MRI concepts integral to successful salvage brachytherapy.