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.

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.

Development of haemophilic arthropathy of the ankle: results of a Delphi consensus survey on potential contributory factors.

The evidence base to support the prevention of haemophilic arthropathy remains incomplete. In particular there is a lack of evidence regarding the potential influence of non-haematological factors. Additionally the ankle joint, the most affected joint in the primary prophylaxis era, has biochemical and structural features that should offer some protection from degeneration. Therefore, this study aimed to ascertain expert opinions on the potential contributory factors in order to inform a research agenda. The Delphi method, a group forum technique to achieve consensus of expert opinion was selected. It allows anonymous participation of a geographically disparate panel. A modified three-round design was used with a multi-professional international panel from 11 countries, 280 suggestions with the potential to influence arthropathy development were submitted in Round 1. These were analysed for theme, giving 47 factors in four categories: musculoskeletal intrinsic, extrinsic affecting physical health, compliance, education and non-haematological management, and haemophilia related. Subsequently, consensus was ascertained on their importance for study. At survey completion, 31 panellists (86%) completed. 41 factors reached the pre-selected level for consensus and 6 were rejected. The breadth of the factors put forward suggests that the panel believe pathogenesis of HA is multifactorial. Panel composition indicates results with high face and content validity capable of guiding future research. Developing an understanding of the relative influence of factors in each patient has the potential of not only individualizing replacement therapy with regard to frequency and trough levels but also individualizing other interventions that promote musculoskeletal health.

A case-control study assessing bone mineral density in severe haemophilia A in the UK.

It has been shown that bone mineral density (BMD) may be lower in patients with haemophilia (PWH). A comparison to control subjects is required to thoroughly assess current BMD in PWH in the UK. The objective of this study was to test the hypothesis that BMD is lower in PWH than in controls, and in patients with more severely affected joints or lower activity levels. In this case-control study, 37 patients with severe haemophilia A were recruited from two haemophilia centres in the UK. A group of 37 age, gender and ethnicity-matched control participants were recruited. All participants had a bone density scan, a musculoskeletal assessment, a blood test for vitamin D and completed a functional activity questionnaire. Of the case group, 5% had osteoporosis and 24% had BMD lower than expected for age. No control participants had osteoporosis, 3% had osteopenia and 14% had BMD lower than expected for age. Ninety one per cent of case participants and 92% of control participants had reduced 25(OH)D levels. Case participants had significantly lower BMD than control participants, and case participants with more severely affected joints, lower activity levels, HIV, history of hepatitis C or lower BMI had significantly lower BMD. Patients with severe haemophilia have a higher risk of low BMD than men without haemophilia. Patients with more severely affected joints and lower activity levels have lower BMD. It remains unclear whether patients with low BMD reached adequate peak bone mass. Low vitamin D may be present in the majority of PWH.

Radiation exposure from diagnostic imaging in young patients with testicular cancer.

OBJECTIVES: Risks associated with high cumulative effective dose (CED) from radiation are greater when imaging is performed on younger patients. Testicular cancer affects young patients and has a good prognosis. Regular imaging is standard for follow-up. This study quantifies CED from diagnostic imaging in these patients. METHODS: Radiological imaging of patients aged 18-39 years, diagnosed with testicular cancer between 2001 and 2011 in two tertiary care centres was examined. Age at diagnosis, cancer type, dose-length product (DLP), imaging type, and frequency were recorded. CED was calculated from DLP using conversion factors. Statistical analysis was performed with SPSS. RESULTS: In total, 120 patients with a mean age of 30.7 ± 5.2 years at diagnosis had 1,410 radiological investigations. Median (IQR) surveillance was 4.37 years (2.0-5.5). Median (IQR) CED was 125.1 mSv (81.3-177.5). Computed tomography accounted for 65.3 % of imaging studies and 98.3 % of CED. We found that 77.5 % (93/120) of patients received high CED (>75 mSv). Surveillance time was associated with high CED (OR 2.1, CI 1.5-2.8). CONCLUSIONS: Survivors of testicular cancer frequently receive high CED from diagnostic imaging, mainly CT. Dose management software for accurate real-time monitoring of CED and low-dose CT protocols with maintained image quality should be used by specialist centres for surveillance imaging. KEY POINTS: • CT accounted for 98.3 % of CED in patients with testicular cancer. • Median CED in patients with testicular cancer was 125.1 mSv • High CED (>75 mSv) was observed in 77.5 % (93/120) of patients. • Dose tracking and development of low-dose CT protocols are recommended.

The role of pure iterative reconstruction in conventional dose CT enterography.

PURPOSE: Pure iterative reconstruction (Pure IR) has been proposed as a solution to improve diagnostic quality of low dose CT images. We assess the performance of model based iterative reconstruction (MBIR) in improving conventional dose CT enterography (CTE) images. METHODS: 43 Crohn's patients (27 female) (38.5 ± 12.98 years) referred for CTE were included. Images were reconstructed with pure IR (MBIR, General Electric Healthcare) in addition to standard department protocol (reconstructed with hybrid iterative reconstruction (Hybrid IR) [60% filtered back projection/40% adaptive statistical IR (General Electric Healthcare)]. Image quality was assessed objectively and subjectively at 6 anatomical levels. Clinical interpretation was undertaken in consensus by 2 blinded radiologists along with 2 non-blinded readers ('gold standard'). Results were analyzed using Statistical Package for Social Scientists. RESULTS: Mean effective radiation dose was 6.05 ± 2.84 mSv (size specific dose estimates 9.25 ± 2.9 mGy). Objective and subjective assessment yielded 6106 data points. Pure IR images significantly outperformed those using standard reconstruction techniques across all subjective (p < 0.001 for all comparisons) (noise, contrast resolution, spatial resolution, streak artifact, axial diagnostic acceptability, coronal diagnostic acceptability) and objective (p < 0.004) (noise, signal-to-noise ratio) parameters. Clinical reads of the pure IR images agreed more closely with the gold standard reads than the hybrid IR image reads in terms of overall Crohn's activity grade (κ = 0.630, 0.308) and detection of acute complications (κ = 1.0, 0.896). Results were comparable for bowel wall disease severity assessment (κ = 0.523, 0.593). CONCLUSIONS: Pure IR considerably improves image quality of conventional dose CTE images and therefore its use should be expanded beyond low dose protocols to improving image quality at conventional dose CT imaging.

Detection of occult, undisplaced hip fractures with a dual-energy CT algorithm targeted to detection of bone marrow edema.

The purpose of this study is to describe our initial clinical experience with dual-energy computed tomography (DECT) virtual non-calcium (VNC) images for the detection of bone marrow (BM) edema in patients with suspected hip fracture following trauma. Twenty-five patients presented to the emergency department at a level 1 trauma center between January 1, 2011 and January 1, 2013 with clinical suspicion of hip fracture and normal radiographs were included. All CT scans were performed on a dual-source, dual-energy CT system. VNC images were generated using prototype software and were compared to regular bone reconstructions by two musculoskeletal radiologists in consensus. Radiological and/or clinical diagnosis of fracture at 30-day follow-up was used as the reference standard. Twenty-one patients were found to have DECT-VNC signs of bone marrow edema. Eighteen of these 21 patients were true positive and three were false positive. A concordant fracture was clearly seen on bone reconstruction images in 15 of the 18 true positive cases. In three cases, DECT-VNC was positive for bone marrow edema where bone reconstruction CT images were negative. Four patients demonstrated no DECT-VNC signs of bone marrow edema: two cases were true negative, two cases were false negative. When compared with the gold standard of hip fracture determined at retrospective follow-up, the sensitivity of DECT-VNC images of the hip was 90 %, specificity was 40 %, positive predictive value was 86 %, and negative predictive value was 50 %. Our initial experience would suggest that DECT-VNC is highly sensitive but poorly specific in the diagnosis of hip fractures in patients with normal radiographs. The value of DECT-VNC primarily lies in its ability to help detect fractures which may be subtle or undetectable on bone reconstruction CT images.

The Victorian Lung Cancer Registry pilot: improving the quality of lung cancer care through the use of a disease quality registry.

BACKGROUND: Lung cancer remains a major disease burden in Victoria (Australia) and requires a complex and multidisciplinary approach to ensure optimal care and outcomes. To date, no uniform mechanism is available to capture standardized population-based outcomes and thereby provide benchmarking. The establishment of such a data platform is, therefore, a primary requisite to enable description of process and outcome in lung cancer care and to drive improvement in the quality of care provided to individuals with lung cancer. MATERIALS AND METHODS: A disease quality registry pilot has been established to capture prospective data on all adult patients with clinical or tissue diagnoses of small cell and non-small cell lung cancer. Steering and management committees provide clinical governance and supervise quality indicator selection. Quality indicators were selected following extensive literature review and evaluation of established clinical practice guidelines. A minimum dataset has been established and training and data capture by data collectors is facilitated using a web-based portal. Case ascertainment is established by regular institutional reporting of ICD-10 discharge coding. Recruitment is optimized by provision of opt-out consent. RESULTS: The collection of a standardized minimum data set optimizes capacity for harmonized population-based data capture. Data collection has commenced in a variety of settings reflecting metropolitan and rural, and public, and private health care institutions. The data set provides scope for the construction of a risk-adjusted model for outcomes. A data access policy and a mechanism for escalation policy for outcome outliers has been established. CONCLUSIONS: The Victorian Lung Cancer Registry provides a unique capacity to provide and confirm quality assessment in lung cancer and to drive improvement in quality of care across multidisciplinary stakeholders.

The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.

BACKGROUND: The objective of this study was to determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT). METHODS: Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose-escalated external-beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined-modality RT (CMRT) consisting of (103) Pd implants (n = 369) or (125) I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer-specific mortality (PCSM) were estimated by using the Kaplan-Meier method and Fine and Gray regression analysis. RESULTS: The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P < .0001) and 7% (standard error 6%-9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P < .0001) and 0.41 (95% CI, 0.23-0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF (P = .04) and PCSM (P = .001), which was greatest with long-term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21-0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15-0.6) even in the subgroup that received CMRT. CONCLUSIONS: In this retrospective comparison, both low-dose-rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT.

The effects of repetitive haemarthrosis on postural balance in children with haemophilia.

Sensory information from visual, vestibular and proprioceptive systems is necessary to control posture and balance. Impairment in proprioception due to repetitive joints bleeding may lead to a deficit in postural balance which, in turn, leads to high joint stress and risk of bleeding recurrence. Despite the increase in attention in this field during the past few years, the data concerning to how bleeds can affect postural control in children with haemophilia (CWH) remain scarce. This study aimed to evaluate the postural balance in CWH. Twenty CWH Haemophilia Group (HG) and 20 age-matched children Control Group (CG) were recruited to this study. A force plate was used to record centre of pressure (COP) displacement under four different postural conditions during quiet standing: eyes open on firm surface, eyes open on foam surface, eyes closed on firm surface and eyes closed on a foam surface. Variables of COP as sway area and mean velocity and in anterior-posterior (y) medio-lateral (x) direction were processed and for each variable sensory, quotients were calculated and compared between groups. No differences were found in visual and vestibular quotients variables between groups. A higher value was found in sway area variable on proprioception quotient in the HG when compared with CG (P = 0.042). CWH with repetitive joint bleed on lower limbs showed differences in postural balance when compared with non-haemophiliac children. The identification of early balance impairments in CWH can help us understand better the effects of bleeds inside joints on postural control and plan a more effective preventive and rehabilitative treatment.

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.

A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. PATIENTS AND METHODS: We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. RESULTS: Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. CONCLUSIONS: Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.

Knee arthropathy: when things go wrong.

Joint bleeding, or haemarthrosis, is the most common type of bleeding episode experienced by individuals with haemophilia A and B. This leads to changes within the joints, including synovial proliferation, which results in further bleeding and chronic synovitis. Blood in the joint can also directly damage the cartilage, and with repeated bleeding, there is progressive destruction of both cartilage and bone. The end result is known as haemophilic arthropathy which is characterized by pain, stiffness and deformity. The joint most commonly affected is the knee. Haemophilic arthropathy can be prevented through regular prophylaxis and physiotherapy. However, when necessary, there are multiple surgical and non-surgical options available. These procedures are indicated to improve the joint function and quality of life for haemophilic patients worldwide. In this review, the role of surgical and non-surgical treatment of advanced knee arthropathy and its complications will be described.

Management of muscle haematomas in patients with severe haemophilia in an evidence-poor world.

Treatment studies in haemophilia focus on joint bleeds; however, some 10-25% of bleeds occur in muscles. This review addresses management of muscle haematoma in severe haemophilia, defines gaps in the published evidence, and presents a combined clinician and physiotherapist perspective of treatment modalities. The following grade 2C recommendations were synthesized: (i) Sport and activity should be based on individual factor levels, bleeding history and physical characteristics, (ii) Musculoskeletal review aids the management of children and adults, (iii) 'Time to full recovery' should be realistic and based on known timelines from the healthy population, (iv) Diagnosis should be carried out by both a clinician and physiotherapist, (v) Severe muscle bleeds should be treated similarly to surgical patients: a 50% trough for 10-14 days followed by high-level prophylaxis, (vi) Protection, rest, ice, compression and elevation should be implemented in the acute stage, and (vii) Physiotherapy and rehabilitation should be divided into: control of haemorrhage (phase 1); restoration of Range of Movement (ROM) and strength (phase 2); functional rehabilitation and return to normal living (phase 3). Recommendations specifically for inhibitor patients include: (i) Minor to moderate bleeds should be managed by home-treatment within 1 h of bleed onset using either one injection of rFVIIa 270 µg kg(-1), or two to three injections of rFVIIa 90 µg kg(-1) (2-3 h intervals), or FEIBA 50-100 U kg(-1) (repeated at 12-hourly intervals, if necessary) and (ii) Severe muscle bleeds should be supervised by the treatment centre and include bypassing agents until clinical improvement is observed.

Effects of abdominal fat distribution parameters on severity of acute pancreatitis.

BACKGROUND: Obesity is a well-established risk factor for acute pancreatitis. Increased visceral fat has been shown to exacerbate the pro-inflammatory milieu experienced by patients. This study aimed to investigate the relationship between the severity of acute pancreatitis and abdominal fat distribution parameters measured on computed tomography (CT) scan. METHODS: Consecutive patients admitted to Cork University Hospital with acute pancreatitis between January 2005 and December 2010 were evaluated for inclusion in the study. An open source image analysis software (Osirix, v 3.9) was used to calculate individual abdominal fat distribution parameters from CT scans by segmentation of abdominal tissues. RESULTS: A total of 214 patients were admitted with pancreatitis between January 2005 and December 2010. Sixty-two of these patients underwent a CT scan and were thus eligible for inclusion. Visceral fat volume was the volumetric fat parameter that had the most significant association with severe acute pancreatitis (P = 0.003). There was a significant association between visceral fat volume and subsequent development of systemic complications of severe acute pancreatitis (P = 0.003). There was a strong association between mortality and visceral fat volume (P = 0.019). Multivariate regression analysis, adjusted for gender, did not identify any individual abdominal fat distribution index as an independent risk factor for severe acute pancreatitis. CONCLUSIONS: Overall, estimation of abdominal fat distribution parameters from CT scans performed on patients with acute pancreatitis indicates a strong association between visceral fat, severe acute pancreatitis, and the subsequent development of systemic complications. These data suggest that visceral fat volume should be incorporated into future predictive scoring systems.

Does Courvoisier's sign stand the test of time?

AIM: To investigate the validity of Courvoisier's sign, in the age of cross-sectional imaging and image analysis software by objectively measuring gallbladder volumes at magnetic resonance cholangiopancreatography (MRCP) in patients with and without biliary obstruction and to assess whether gallbladder volume is more significantly increased in patients with gallstone-related rather than non-gallstone-related biliary obstruction. MATERIALS AND METHODS: All MCRP investigations that were performed at a tertiary hepatobiliary centre over a 2-year period were analysed. The information recorded included the presence or absence of gallbladder stones as well as the presence and type of common bile duct (CBD) disease. Gallbladder volume was calculated from MRCP studies using image analysis software. RESULTS: Three hundred and ninety-four of 645 examined MRCPs (61.1%) were eligible for analysis. A statistically significant difference in mean gallbladder volume existed between the summated obstructive and non-obstructive groups (p < 0.001). In addition, a significant difference existed in mean gallbladder volume between those with CBD stones and non-gallstone CBD obstruction (p = 0.03). CONCLUSION: A significant difference was observed in gallbladder volumes in the group with biliary obstruction from choledocholithiasis compared with the group with biliary obstruction from other causes. Thus, objective measurement of gallbladder volume from modern cross-sectional imaging studies appears to validate Courvoisier's sign as a valuable clinical sign, which could be applied to modern imaging studies in distinguishing different causes of biliary obstruction in the jaundiced patient.

Outbreak of abdominal distension and obstipation in a C57BL/6J experimental autoimmune encephalomyelitis study.

Seventy-four 9-week old female C57BL/6J mice housed in a conventional facility were manipulated to induce experimental autoimmune encephalomyelitis, among which 26 developed clinical signs including lethargy, absence of defecation, and abdominal distension. By gross necropsy examination, there was distension of the cecum and colon with fecal impaction. By histologic examination, there was severe ulcerative and proliferative typhlocolitis. Fecal ELISA confirmed the presence of toxins A and B of Clostridium difficile. Alteration in immune status of the immunocompetent mice, due to stress caused by experimental manipulation or autoimmune disease, may have led to intestinal dysbiosis, followed by opportunistic infections resulting in C. difficile-associated disease. This report brings to light the occurrence of the disease in immunocompetent laboratory mice during experimental manipulations associated with alteration in immune status, and it discusses potential hazards associated with conventional housing within a hospital-associated research institute.

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.