732-1 An Institutional Experience with Second and Third Stage Palliative Procedures for Hypoplastic Left Heart Syndrome: The Impact of the Bidirectional Cavopulmonary Shunt

We reviewed 71 consecutive pts who underwent stage II and III operations following stage I palliation for hypoplastic left heart syndrome (HLHS) at our institution since 1983. 6 surgeons participated in the care of these pts. Follow-up is 97% complete. We examined 17 potential risk factors for mortality, including preoperative anatomic and physiologic factors, and procedural features of the stage II operation. Multivariate analysis revealed that the only significant risk factor for stage II mortality was the performance of a non-fenestrated completion Fontan procedure (p<0.001). There were 9 hospital deaths (69%) in the 13 pts undergoing the Fontan procedure at stage II. In contrast, 49 pts underwent bidirectional cavopulmonary shunting (47) or hemi-Fontan procedure(2) as an intermediate step to the Fontan procedure with 4 (8%) early deaths. The first bidirectional cavopulmonary shunt was performed in this population in 1988. Median age at this stage II procedure was 8.4 months. Surgical augmentation of the pulmonary arteries was performed in 18 (37%) pts at the time of stage II surgery and was not associated with increased operative risk. Also, HLHS anatomic subtype was not a risk factor for stage II mortality or pre-stage III attrition. There have been 2 (4%) intermediate deaths prior to the performance of a stage III procedure, which at our institution is the fenestrated Fontan procedure. This has been performed in 25 pts at a median age of 30 months with 1 early death and no mortality at a median follow-up of 22 months. There are presently 34 HLHS pts who have modified Fontan anatomy following a course of surgical palliation performed entirely at this institution. Follow-up in this group ranges up to 92 months, with a median of 28 months. 33 of these patients are NYHA class 1 or 2.2 pts have required pacemaker implantation, but there have otherwise been no surgical reinterventions in pts who have completed palliation. We conclude that the incorporation of the bidirectional cavopulmonary shunt into a course of surgical palliation for HLHS has dramatically reduced mortality in this challenging group of pts, allowing them to undergo the modified fenestrated Fontan procedure with low operative mortality and good intermediate outcome

Older parents of people who have a learning disability : perceptions of future accomodation needs

The aim of this qualitative study was to provide an insight into the perceptions of older parents of learning disabled people on the future accommodation needs of their adult children. Semi-structured interviews were used to seek parental awareness of residential options available, concerns in relation to future accommodation and the preferred accommodation options for their offspring. Four couples who shared the family home with an adult who has a learning disability took part in the study and data was analysed using a step by step form of content analysis as described by Burnard (1991). Emergent themes from transcripts were then organised into main categories The results of this study suggest that older parents are dissatisfied with both statutory and private services, that they have concerns for their non-disabled children and their own ageing. Being a parent to a person who has a learning disability is seen to be a difficult task and yet parents may want to provide support at home for as long a possible. Of the parents who participated in this study, three couples wanted to maintain their adult child at home for as long as possible and the parents who were actively seeking accommodation outside the family home expected to be involved in all aspects of their daughter�s care for the long term future

A Comparative Computer Simulation of Dendritic Morphology

Computational modeling of neuronal morphology is a powerful tool for understanding developmental processes and structure-function relationships. We present a multifaceted approach based on stochastic sampling of morphological measures from digital reconstructions of real cells. We examined how dendritic elongation, branching, and taper are controlled by three morphometric determinants: Branch Order, Radius, and Path Distance from the soma. Virtual dendrites were simulated starting from 3,715 neuronal trees reconstructed in 16 different laboratories, including morphological classes as diverse as spinal motoneurons and dentate granule cells. Several emergent morphometrics were used to compare real and virtual trees. Relating model parameters to Branch Order best constrained the number of terminations for most morphological classes, except pyramidal cell apical trees, which were better described by a dependence on Path Distance. In contrast, bifurcation asymmetry was best constrained by Radius for apical, but Path Distance for basal trees. All determinants showed similar performance in capturing total surface area, while surface area asymmetry was best determined by Path Distance. Grouping by other characteristics, such as size, asymmetry, arborizations, or animal species, showed smaller differences than observed between apical and basal, pointing to the biological importance of this separation. Hybrid models using combinations of the determinants confirmed these trends and allowed a detailed characterization of morphological relations. The differential findings between morphological groups suggest different underlying developmental mechanisms. By comparing the effects of several morphometric determinants on the simulation of different neuronal classes, this approach sheds light on possible growth mechanism variations responsible for the observed neuronal diversity

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability