Diagnosis of a biliary cystadenoma demonstrating communication with the biliary system by MRI using a hepatocyte-specific contrast agent.

Biliary cystadenomas are predominately benign tumours that have a low malignant potential. We present a case of a 30-year-old female with a histopathological confirmation of a biliary cystadenoma following resection. The diagnosis was made pre-operatively by MRI using the hepatocyte-specific contrast agent gadobenate dimeglumine (Gd-BOPTA) (MultiHance; Bracco Diagnostics Inc., Princeton, NJ). At the biliary excretory phase, delayed phase images demonstrated communication between the multilocular cystic mass and the biliary tree, which helped to confirm the diagnosis of biliary cystadenoma. This highlights the beneficial use of hepatocyte-specific agents for their dual function as an extracellular agent and a hepatobiliary agent.

The Anaconda AAA stent graft system: 2-year clinical and technical results of a multicentre clinical evaluation.

INTRODUCTION: This study reports the technical and mid-term clinical results of the second-generation Anaconda AAA Stent Graft System endovascular device for treatment of abdominal aortic aneurysm (AAA). The design of the Anaconda AAA Stent Graft System is characterised by a three-piece system consisting of two proximal independent saddle-shaped nitinol self-expandable rings with hooks fixation, zero body support and vacuum-cleaner tube leg design. METHODS: From July 2002 to April 2005, a total of 61 patients with AAA were enrolled in a multicentre, prospective, non-randomised controlled design study. All patients received a second-generation Anaconda AAA Stent Graft System. They entered a standard follow-up protocol at discharge for 3, 6, 12 and 24 months. Follow-up data included survival; rupture-free survival; incidence of aneurysm rupture, death from aneurysm rupture, aneurysm-related death; freedom from aneurysm expansion; freedom from Types I and III endoleaks; endograft patency and technical and clinical success rates. RESULTS: Successful access to the arterial system was achieved in all patients. The primary technical success was 59 out of 61 and the primary assisted technical success was 60 out of 61. All endovascular grafts were patent without significant twists, kinks or obstructions. Migration was not observed in any of the grafts. During the first 30-day period, two serious adverse events (3%), both not related to the procedure, were observed. Nine patients (15%) needed a secondary intervention; two of these interventions were related to stent graft (3%). The mean aneurysm sac diameter decreased significantly from 57 mm pre-operative to 45mm after 24 months, without aneurysm growth. There was one Type I endoleak at initial implantation, which was corrected using a proximal extension cuff. In total, three Type II endoleaks were still present after 24 months without any signs of aneurysm growth. CONCLUSION: The design features of the second-generation Anaconda AAA Stent Graft System are effective in the treatment of AAAs on mid-term evaluation.

Cutaneous epithelioid angiomatous nodule: different views or interpretations in the analysis of ten new cases.

Classification schemes proposed for vascular lesions are the subjects of significant controversy. Cutaneous epithelioid angiomatous nodule (CEAN) was described in 2004, but there is no agreement as to whether this is a distinct entity or a type of either epithelioid hemangioma or angiolymphoid hyperplasia with eosinophilia. We present a typical case of CEAN and discuss nine other cases from our institution. We then provide two opposing viewpoints concerning its classification.

Hormone replacement therapy (HRT) or etidronate for osteoporosis in postmenopausal asthmatics on glucocorticoids: a randomised factorial trial.

INTRODUCTION: The study was designed to establish the effects of HRT on osteoporosis and fractures over five years in postmenopausal women with asthma receiving regular glucocorticoids and to compare with etidronate. METHODS: Postmenopausal patients receiving inhaled and/or oral glucocorticoids were randomly assigned to HRT, cyclical etidronate, HRT plus cyclical etidronate or no treatment for five years. The trial was multi-centre and aimed to recruit 750 patients. Outcomes were fractures and changes in bone mineral density (BMD). RESULTS: For reasons detailed in the discussion section of the text, only 50 patients were entered. Three did not fulfil the eligibility criteria and were excluded from the analysis. Among the remaining 47 patients, three (6%) experienced new, symptomatic fractures, one on etidronate and two in the no treatment group. New or worsening morphometric fractures of the thoracolumbar spine occurred in 50% of the 22 patients with spinal radiographs on entry and at five years (one HRT, three etidronate, two HRT plus etidronate and five on no treatment). BMD improved by approximately 1% per annum in those receiving HRT and/or etidronate; comparisons of HRT vs no HRT tended to favour HRT but were only statistically significant at proximal femur. The same trends emerged in the etidronate vs no etidronate comparison, but none reached the 5% level of statistical significance. DISCUSSION: For postmenopausal patients receiving glucocorticoids for asthma, HRT appears as effective as etidronate in preventing loss of BMD over five years and may have a similar effect on fracture prevention.

Gallbladder sarcoma: a clinicopathological study of seven cases from the UK and Austria with emphasis on morphological subtypes.

BACKGROUND: Primary sarcoma of the gallbladder (PGBS) is rare, with only 40 cases reported in the literature. Most of these have been diagnosed as leiomyosarcoma. We aimed to evaluate the histological features of a case series of this rare tumor and correlate these with clinical features. DESIGN: Cases recorded as "gallbladder sarcoma" from different institutes were reviewed and the clinicopathological features of these cases were recorded. Only primary gallbladder wall mesenchymal tumors were included. Epithelial tumors, mixed tumors (carcinosarcoma or sarcomatoid carcinoma), and tumors extending into the gallbladder from the abdomen or sarcoma with other known primaries were specifically excluded. RESULT: PGBS occurred in one male and six females with a median age of 70 (range 64-82) years. Patients presented with acute or chronic cholecystitis, abdominal pain, weight loss, and pruritus. They were generally found to have elevated alkaline phosphatase and bilirubin, and leukocytosis. Tumors ranged from 1.1 to 4 cm with a median size of 3 cm. Most PGBS arose in the body but one arose in the fundus. All tumors were associated with ulcerated mucosa. Based on morphological and immunohistochemical features of the PGBS, there were three myxofibrosarcomas (malignant fibrous histiocytoma, MFH, storiform pleomorphic), one leiomyosarcoma (LMS), one angiosarcoma (AS), and two liposarcomas (LS). All patients received cholecystectomy and three received adjuvant chemotherapy. Follow-up revealed that six patients died of the disease 6 weeks to 2 years after diagnosis and one died of unrelated causes. CONCLUSION: PGBS are rare and mainly occur in the gallbladder body in middle-aged females. They generally present with acute cholecystitis and have a very poor prognosis. A variety of sarcoma types are found with MFH being the predominant variant.

A re-appraisal of warfarin control in the treatment of deep vein thrombosis and / or pulmonary embolism.

BACKGROUND: Warfarin is commonly used for management of deep vein thrombosis (DVT) and pulmonary embolism (PE), controlling therapy by means of the International Normalized Ratio (INR). OBJECTIVES: To identify differences in INR results between patients with thromboembolic and haemorrhagic complications and controls. METHODS: Two nested case-control studies from within a controlled trial of the duration of warfarin therapy (47 thrombotic and 16 haemorrhagic complications). RESULTS: Patients whose thromboembolism failed to resolve during treatment or recurred during or after treatment had non-significantly lower INR levels than matched controls (geometric mean 2.2 versus 2.3, p = 0.12). Patients with haemorrhage also had not statistically significant lower INR levels than their matched controls (2.1 versus 2.3, p = 0.22). The variability of INR levels was similar in both case groups and controls. The mean percentage of INR levels in the therapeutic range 2 - 3 was almost identical in thrombotic cases and controls (56.5% versus 56.1%). Compared to the haemorrhagic group, better control was achieved in controls (61.5% versus 43.0%, p=0.01), but controls had slightly more INR values above the therapeutic range (12.1% versus 10.5%, p = 0.74) whilst haemorrhagic cases had more INR values below the therapeutic range (46.6% versus 26.4%, p = 0.03). CONCLUSION: In this study, higher INR levels were not associated with haemorrhage suggesting that, for patients being treated for DVT/PE, a modest increase in the target therapeutic range could be considered.

Implementation of NICE recommendation for a policy of routine antenatal anti-D prophylaxis: a survey of UK maternity units.

The aim of this study was to determine how many UK maternity units have implemented National Institute for Clinical Excellence (NICE) guidance for routine antenatal anti-D prophylaxis (RAADP). In May 2002, the NICE recommended a policy of RAADP for RhD-negative pregnant women. The policy has the potential to reduce maternal sensitization and prevent deaths from haemolytic disease of the foetus and newborn, but implementation entails considerable clinical, financial and organizational challenges. A postal survey of all 324 UK maternity units was completed in 2005.Responses were received from 91% of units (294 of 324). RAADP was offered by 220 of 294 (75%) and in England and Wales 19% of those offered a single-dose regime. At 12% of maternity units, routine paternal blood group testing was offered. For 84% of maternity units, staff education was offered at the time of implementation. Written patient information was provided at 97% of maternity units and 147 of 217 (69%) returned a copy. We received 60 different leaflets. Three years after NICE guidance was issued, one in four maternity units did not offer RAADP. Among those that do offer RAADP, practice with regard to anti-D administration, paternal testing, provision of written information and staff education varied. Unit and clinician level research is required to understand why.

Superficial acral fibromyxoma: a clinicopathological study of new 41 cases from the U.K.: should myxoma (NOS) and fibroma (NOS) continue as part of 21st-century reporting?

BACKGROUND: Superficial acral fibromyxoma (SAF) remains poorly recognized by general pathologists and dermatopathologists, partly attributable to its relatively uncommon occurrence and recent documentation. OBJECTIVES: To examine a series of SAF and document the U.K. experience with this new entity. METHODS: We reviewed 771 tumours reported between 1970 and 2006 in seven different U.K. hospitals and coded as myxoma, not otherwise specified (NOS), fibroma (NOS) or dermatofibroma (NOS) presenting at acral sites. Forty-one cases of SAF were studied. RESULTS: The patients comprised 27 men and 14 women, age range 19-91 years (mean 50, median 47), presenting with a solitary mass or nodule with a mean size of 1.92 cm. The common clinical sites were the toes (n=29) and fingers (n=11) as well as the palm (n=1), with more than 75% of cases close to or involving the nail bed. All cases presented with a painless mass except for four cases where pain was the presenting complaint. A history of trauma was reported in only two cases. Histologically, all cases presented as proliferation of spindle-shaped and/or stellate cells with a storiform and fascicular pattern embedded in a fibromyxoid/collagenous stroma with conspicuous mast cells. Multinucleated cells were observed (n=22), increased number of blood vessels in the stroma and extravasation of red blood cells (n=4). The characteristic immunophenotype was CD34+, CD99+/-, epithelial membrane antigen+ focally/-, S100-, desmin-, smooth muscle actin-, HMB45- and cytokeratin-. CONCLUSIONS: We describe a large series of 41 cases of SAF showing that it is a distinct entity with typical clinical, histological and immunohistochemical features. Follow-up was available only in 12 patients, precluding a firm comment on recurrence. However, complete excision and follow-up review is recommended.

Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy.

BACKGROUND: The mainstays of treatment for pulmonary disease caused by opportunist mycobacteria are rifampicin (R) and ethambutol (E). The role of macrolides, quinolones and immunotherapy with Mycobacterium vaccae is not clear. A trial was undertaken to compare clarithromycin (Clari) and ciprofloxacin (Cipro) as third drugs added to [corrected] 2 years of treatment with R and E for pulmonary disease caused by M avium-intracellulare (MAC), M malmoense and M xenopi (REClari and RECipro). An optional comparison of immunotherapy with M vaccae vs no immunotherapy was also performed. METHODS: Progress was monitored annually during the 2 years of treatment and for 3 years thereafter. If the patient was not improving at 1 year the regimen was supplemented by the addition of the drug not received in the original allocation of treatment. RESULTS: 371 patients (186 REClari, 185 RECipro) entered the study (170 MAC, 167 M malmoense, 34 M xenopi). All-cause mortality was high for both groups (44% REClari, 43% RECipro); for MAC it was higher with REClari than with RECipro (48% vs 29%) but for M malmoense (42% vs 56%) and M xenopi (29% vs 47%) it was higher with RECipro (p = 0.006). 3% died from their mycobacterial disease (REClari = RECipro). At the end of treatment, 4% of REClari and 10% of RECipro patients still had positive cultures. Among those with negative cultures at the end of treatment, 6% of the REClari group and 4% of the RECipro group had relapsed. At 5 years 30% of the REClari group were known to have completed treatment as allocated and to be alive and cured compared with 21% of the RECipro group (p = 0.04), but this difference was principally due to those with M malmoense (REClari 38%, RECipro 20%). Patients with MAC or M xenopi were more likely to have a poor outcome than those with M malmoense (p = 0.004), with no difference between REClari and RECipro. Overall, 20% in each group were unable to tolerate the regimen allocated, Cipro being associated with more unwanted effects than Clari (16% vs 9%, p = 0.05). No significant differences in outcomes were found between M vaccae-treated patients and those not treated with M vaccae immunotherapy. CONCLUSION: Considering all three species together, there were no differences in outcome between the REClari and RECipro groups. Immunotherapy did not improve outcome. New therapies, optimised management of co-morbid conditions and a more holistic approach must be explored in the hope of improving outcome.

TELEMAM: a cluster randomised trial to assess the use of telemedicine in multi-disciplinary breast cancer decision making.

AIM: The TELEMAM trial aimed to assess the clinical effectiveness and costs of telemedicine in conducting breast cancer multi-disciplinary meetings (MDTs). METHODS: Over 12 months 473 MDT patient discussions in two district general hospitals (DGHs) were cluster randomised (2:1) to the intervention of telemedicine linkage to breast specialists in a cancer centre or to the control group of 'in-person' meetings. Primary endpoints were clinical effectiveness and costs. Economic analysis was based on a cost-minimisation approach. RESULTS: Levels of agreement of MDT members on a scale from 1 to 5 were high and similar in both the telemedicine and standard meetings for decision sharing (4.04 versus 4.17), consensus (4.06 versus 4.20) and confidence in the decision (4.16 versus 4.07). The threshold at which the telemedicine meetings became cheaper than standard MDTs was approximately 40 meetings per year. CONCLUSION: Telemedicine delivered breast cancer multi-disciplinary meetings have similar clinical effectiveness to standard 'in-person' meetings.

A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial.

OBJECTIVES: To assess whether omission of postoperative radiotherapy in women with 'low-risk' axillary node negative breast cancer (T0-2) treated by breast-conserving surgery and endocrine therapy improves quality of life and is more cost-effective. DESIGN: A randomised controlled clinical trial, using a method of minimisation balanced by centre, grade of cancer, age, lymphatic/vascular invasion and preoperative endocrine therapy, was performed. A non-randomised cohort was also recruited, in order to complete a comprehensive cohort study. SETTING: The setting was breast cancer clinics in cancer centres in the UK. PARTICIPANTS: Patients aged 65 years or more were eligible provided that their cancers were considered to be at low risk of local recurrence, were suitable for breast-conservation surgery, were receiving endocrine therapy and were able and willing to give informed consent. INTERVENTIONS: The standard treatment of postoperative breast irradiation or the omission of radiotherapy. MAIN OUTCOME MEASURES: Quality of life was the primary outcome measure, together with anxiety and depression and cost-effectiveness. Secondary outcome measures were recurrence rates, functional status, treatment-related morbidity and cosmesis. The principal method of data collection was by questionnaire, completed at home with a research nurse at four times over 15 months. RESULTS: The hypothesised improvement in overall quality of life with the omission of radiotherapy was not seen in the EuroQol assessment or in the functionality and symptoms summary domains of the European Organisation for Research in the Treatment of Cancer (EORTC) scales. Some differences were apparent within subscales of the EORTC questionnaires, and insights into the impact of treatment were also provided by the qualitative data obtained by open-ended questions. Differences were most apparent shortly after the time of completion of radiotherapy. Radiotherapy was then associated with increased breast symptoms and with greater fatigue but with less insomnia and endocrine side-effects. Patients had significant concerns about the delivery of radiotherapy services, such as transport, accommodation and travel costs associated with receiving radiotherapy. By the end of follow-up, patients receiving radiotherapy were expressing less anxiety about recurrence than those who had not received radiotherapy. Functionality was not greatly affected by treatment. Within the randomised controlled trial, the Barthel Index demonstrated a small but significant fall in functionality with radiotherapy compared with the no radiotherapy arm of the trial. Results from the non-randomised patients did not confirm this effect, however. Cosmetic results were better in those not receiving radiotherapy but this did not appear to be an important issue to the patients. The use of home-based assessments by a research nurse proved to be an effective way of obtaining high-quality data. Costs to the NHS associated with postoperative radiotherapy were calculated to be of the order of 2000 pounds per patient. In the follow-up in this study, there were no recurrences, and the quality of life utilities from EuroQol were almost identical. CONCLUSIONS: Although there are no differences in overall quality of life scores between the patients treated with and without radiotherapy, there are several dimensions that exhibit significant advantage to the omission of irradiation. Over the first 15 months, radiotherapy for this population is not a cost-effective treatment. However, the early postoperative outcome does not give a complete answer and the eventual cost-effectiveness will only become clear after long-term follow-up. Extrapolations from these data suggest that radiotherapy may not be a cost-effective treatment unless it results in a recurrence rate that is at least 5% lower in absolute terms than those treated without radiotherapy. Further research is needed into a number of areas including the long-term aspects of quality of life, clinical outcomes, costs and consequences of omitting radiotherapy.

Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both: randomised trial.

OBJECTIVE: To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both. DESIGN: Multicentre, prospective, randomised study with follow-up for one year. SETTING: 46 hospitals in United Kingdom. PARTICIPANTS: Patients aged > or =18 with deep vein thrombosis or pulmonary embolism, or both. INTERVENTIONS: Three (n=369) or six months (n=380) of anticoagulation with heparin for five days accompanied and followed by warfarin, with a target international normalised ratio of 2.0-3.5. MAIN OUTCOME MEASURES: Death from deep vein thrombosis or pulmonary embolism; failure to resolve, extension, recurrence of during treatment; recurrence after treatment; and major haemorrhage during treatment. RESULTS: In the patients allocated to three months' treatment two died from deep vein thrombosis or pulmonary embolism during or after treatment, compared with three in the six month group. During treatment deep vein thrombosis or pulmonary embolism failed to resolve, extended, or recurred in six patients in the three month group without fatal consequences, compared with 10 in the six month group. After treatment there were 23 non-fatal recurrences in the three month group and 16 in the six month group. Fatal and non-fatal deep vein thrombosis or pulmonary embolism during treatment, and after treatment thus occurred in 31(8%) of those who had received three months' anticoagulation compared with 29 (8%) of those who had received six months' (P=0.80, 95% confidence interval for difference -3.1% to 4.7%). There were no fatal haemorrhages during treatment but there were eight major haemorrhages in those treated for six months and none in those treated for three months (P=0.008, -3.5% to -0.7%). Thus 31 (8%) of the patients receiving three months' anticoagulation experienced adverse outcomes as a result of deep vein thrombosis or pulmonary embolism or its treatment compared with 35 (9%) of those receiving six months' (P=0.79, -4.9% to 3.2%). CONCLUSION: For patients in the UK with deep vein thrombosis or pulmonary embolism and no known risk factors for recurrence, there seems to be little, if any, advantage in increasing the duration of anticoagulation from three to six months. Any possible advantage would be small and would need to be judged against the increased risk of haemorrhage associated with the longer duration of treatment with warfarin. TRIAL REGISTRATION: Clinical Trials NCT00365950 [ClinicalTrials.gov].

Effects of changing clinical practice on costs and outcomes of percutaneous coronary intervention between 1998 and 2002.

AIM: To assess the effect of changing clinical practice on the costs and outcomes of percutaneous coronary intervention (PCI) between 1998 and 2002. SETTING: Two tertiary interventional centres. PATIENTS: Consecutive patients undergoing PCI over a 12-month period between 1998 and 2002. DESIGN: Comparative observational study of costs and 12-month clinical outcomes of consecutive PCI procedures in 1998 (n = 1047) and 2002 (n = 1346). Clinical data were recorded in the Scottish PCI register. Repeat PCI, coronary artery bypass graft and mortality were obtained by record linkage. Costs of equipment were calculated using a computerised bar-code system and standard National Health Service reference costs. RESULTS: Between 1998 and 2002, the use of bare metal stents increased from 44% to 81%, and the use of glycoprotein IIB/IIIA inhibitors increased from 0% to 14% of cases. During this time, a significant reduction was observed in repeat target-vessel PCI (from 8.4% to 5.1%, p = 0.001), any repeat PCI (from 11.7% to 9.2%, p = 0.05) and any repeat revascularisation (from 15.1% to 11.3%, p = 0.009) within 12 months. Significantly higher cost per case in 2002 compared with 1998 (mean (standard deviation) 2311 pounds (1158) v 1785 pounds (907), p<0.001) was mainly due to increased contribution from bed-day costs in 2002 (45.0% (16.3%) v 26.2% (12.6%), p = 0.01) associated with non-elective cases spending significantly longer in hospital (6.22 (4.3) v 4.6 (4.3) days, p = 0.01). CONCLUSIONS: Greater use of stents and glycoprotein IIb/IIIa inhibitors between 1998 and 2002 has been accompanied by a marked reduction in the need for repeat revascularisation. Longer duration of hospital stay for non-elective cases is mainly responsible for increasing costs. Strategies to reduce the length of stay could considerably reduce the costs of PCI.

The addition of oral idarubicin to a chlorambucil/dexamethasone combination has a significant impact on time to treatment failure but none on overall survival in patients with low grade non-Hodgkin's lymphoma: Results of the Scotland and Newcastle Lymphoma Group randomized NHL VIII trial.

Two hundred untreated patients with low grade NHL (KIEL), including 155 follicular NHL, were randomized to six courses of treatment with chlorambucil 20 mg m-2 for 3 days and dexamethasone 4 mg bd for 5 days (CD) vs the same regimen plus oral idarubicin 10 mg m-2 for 3 days (CID). Responding patients could be randomized to no further treatment or maintenance treatment for up to 36 months with alpha interferon. Complete remissions/CRu were more frequent in the CID arm (35% vs 24%) but the overall response rate was similar; 87/91 (96%) vs 86/92 (93%). Overall survival (OS) did not differ between the two arms. Time to treatment failure (TTTF) was prolonged in the CID arm, p = 0.03; median time 28 vs 19 months. TTTF for the B-cell follicular group alone was for CID (77 patients) 33 months vs 18 months for CD (78 patients). Interferon conferred no apparent benefit. The Follicular Lymphoma International Prognostic Index (FLIPI) is confirmed as a good predictor of risk groups including a group of 23% with shorter survival. The addition of the oral anthracycline, idarubicin, led to a significant improvement in TTTF with low toxicity. The use of radiotherapy in this sub-group may have contributed to this result. CID is a potential for combination with antibody therapy particularly in older patient groups.

The impact of organ failures and their relationship with outcome in intensive care: analysis of a prospective multicentre database of adult admissions.

The database of a multicentre cohort study was analysed to determine the impact of intensive care unit (ICU) organ failures and their association with ICU mortality using sequential organ failure assessment (SOFA). A consecutive sample of 873 adult patients with a non-neurological diagnosis was identified. SOFA scores were measured every 24 h of ICU stay. The odds of ICU death within 7 days doubled (95% CI 1.3-2.9) for a 5-unit increase in total SOFA score at admission, p < 0.001. However ICU death after 7 days was not associated with total SOFA score at admission, p = 0.36. Compared to patients with a day 6 total SOFA score = 5, there was a 1-unit (95% CI 0.8-3.1) increase in the odds ratio of ICU death after 7 days with every 5-unit increase in SOFA score on day 6, p = 0.009. Continuous assessments of organ failures during an ICU admission are more useful than scores measured at admission to determine outcome and to compare ICUs.

Variations in clinical decision-making between cardiologists and cardiac surgeons; a case for management by multidisciplinary teams?

OBJECTIVE: To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons DESIGN: Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. RESULTS: Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively). CONCLUSION: In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel.

When may adjuvant radiotherapy be avoided in operable breast cancer?

Randomised trials in which the omission of radiotherapy has been tested after breast-conserving surgery, with or without adjuvant systemic therapy, show a significant four- to five-fold reduction in local recurrence. As yet, no subgroup of women managed by breast-conserving surgery has been identified from whom radiotherapy can be withheld. Few randomised data have been published on the effect of omission of radiotherapy on local control, quality of life and costs, particularly in older women for whom the risk of local recurrence is generally lower. Ongoing trials are evaluating the role of radiotherapy in this population of low risk, older women. Adjuvant radiotherapy after breast-conserving surgery or mastectomy significantly reduces the incidence of local recurrence. In women who have had a mastectomy at high risk of recurrence (> 20% risk of recurrence at 10 years), adjuvant radiotherapy improves survival if combined with adjuvant systemic therapy. Among women with T3 tumours, and those with four or more involved axillary nodes treated by mastectomy, postoperative radiotherapy is the standard of care. For women at intermediate risk of recurrence (i.e. <15% 10-year risk of recurrence after surgery and systemic therapy alone), with one to three involved nodes or node negative with other risk factors, the role of radiotherapy is unclear. Clinical trials to assess the role of postmastectomy radiotherapy (PMRT) in this setting are needed. For pT1-2, pNO tumours without other risk factors, there is no evidence at present that PMRT is needed.

People with MECP2 mutation-positive Rett disorder who converse.

BACKGROUND: People with useful speech after regression constitute a distinct group of those with mutation-positive Rett disorder, 6% (20/331) reported among mutation-positive people in the British Survey. We aimed to determine the physical, mental and genetic characteristics of this group and to gain insight into their experience of Rett syndrome. METHODS: Clinical and molecular data for people with Rett, aged 10 or more years at follow-up (the study group, n = 13), with the ability to converse and a MECP2 mutation are presented. They were compared with an age-matched control group (n = 110), who could not converse and had a pathogenic MECP2 mutation. RESULTS: The study group differed significantly from the control group with regard to their disease severity (P < 0.001); feeding difficulty scores (P < 0.001); health scores (P < 0.001); epilepsy (P < 0.001); head circumference (P < 0.004); age at onset of the regression period (P < 0.001) (six in the study group did not regress) and mutation frequency (C-terminal deletions P = 0.014, R133C P < 0.006). The results indicate that favourable skewing of X-inactivation is only present in a small proportion of mild cases. Speech was fragmented with a soft, breathless quality, and all but two had obviously irregular breathing. One person with an R168X mutation preferred signing to speech. All enjoyed interpersonal contact, showing affection and preferring people to objects, clearly distinguishing the condition from autism. Most were habitually anxious. Music was a source of pleasure and relaxation also providing a valuable educational asset. Even in these most able cases, understanding was severely restricted in most and little initiative was shown. CONCLUSIONS: While the Rett profile is present in these people they are commonly not classic, and the presence of speech, good head growth and lack of regression may lead to missed diagnoses. A strong association was demonstrated between this milder form of the disease and R133C and C-terminal deletions.

Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial.

OBJECTIVES: To evaluate the effect of intensive lipid-lowering treatment on coronary artery calcification in a substudy of a trial recruiting patients with calcific aortic stenosis. METHODS: In a double blind randomised controlled trial, 102 patients with calcific aortic stenosis and coronary artery calcification were randomly assigned by the minimisation technique to atorvastatin 80 mg daily or matched placebo. Coronary artery calcification was assessed annually by helical computed tomography. RESULTS: 48 patients were randomly assigned to atorvastatin and 54 to placebo with a median follow up of 24 months (interquartile range 24-30). Baseline characteristics and coronary artery calcium scores were similar in both groups. Atorvastatin reduced serum low density lipoprotein cholesterol (-53%, p < 0.001) and C reactive protein (-49%, p < 0.001) concentrations whereas there was no change with placebo (-7% and 17%, p > 0.95 for both). The rate of change in coronary artery calcification was 26%/year (0.234 (SE 0.037) log arbitrary units (AU)/year; n = 39) in the atorvastatin group and 18%/year (0.167 (SE 0.034) log AU/year; n = 49) in the placebo group, with a geometric mean difference of 7%/year (95% confidence interval -3% to 18%, p = 0.18). Serum low density lipoprotein concentrations were not correlated with the rate of progression of coronary calcification (r = 0.05, p = 0.62). CONCLUSION: In contrast to previous observational studies, this randomised controlled trial has shown that, despite reducing systemic inflammation and halving serum low density lipoprotein cholesterol concentrations, statin treatment does not have a major effect on the rate of progression of coronary artery calcification.