Retrieval of critically ill adults using extracorporeal membrane oxygenation: the nine-year experience in New South Wales.

In New South Wales, a coordinated extracorporeal membrane oxygenation (ECMO) retrieval program has been in operation since 2007. This study describes the characteristics and outcomes of patients transported by this service. We performed a retrospective observational study and included patients who were transported on ECMO to either of two adult tertiary referral hospitals in Sydney, New South Wales, between February 28, 2007 and February 29, 2016. One hundred and sixty-four ECMO-facilitated transports occurred, involving 160 patients. Of these, 118 patients (74%) were treated with veno-venous (VV) ECMO and 42 patients (26%) were treated with veno-arterial ECMO. The mean (standard deviation, SD) age was 40.4 (15.0) years. Seventy-seven transports (47%) occurred within metropolitan Sydney, 52 (32%) were from rural or regional areas within NSW, 17 (10%) were interstate transfers and 18 (11%) were international transfers. Transfers were by road (58%), fixed wing aircraft (27%) or helicopter (15%). No deaths occurred during transport. The median (interquartile range) duration of ECMO treatment was 8.9 (5.2-15.3) days. One hundred and nineteen patients (74%) were successfully weaned from ECMO and 109 (68%) survived to hospital discharge or transfer. In patients treated with VV ECMO, age, sequential organ failure assessment score, pre-existing immunosuppressive disease, pre-existing diabetes, renal failure requiring dialysis and failed prone positioning prior to ECMO were independently associated with increased mortality. ECMO-facilitated patient transport is feasible, safe, and results in acceptable short-term outcomes. The NSW ECMO Retrieval Service provides specialised support to patients with severe respiratory and cardiovascular illness, who may otherwise be too unstable to undergo inter-hospital transfer to access advanced cardiovascular and critical care services.

The expanding role of extracorporeal membrane oxygenation retrieval services in Australia.

Herein we detail the cases of three patients transferred on veno-arterial extracorporeal membrane oxygenation (VA ECMO) from a tertiary referral hospital to an ECMO centre. We highlight the benefits of such a transfer and offer this as a model of care for unwell patients likely to require a prolonged period of ECMO support.

ESHRE Guideline: management of women with premature ovarian insufficiency.

STUDY QUESTION: What is the optimal management of women with premature ovarian insufficiency (POI) based on the best available evidence in the literature? SUMMARY ANSWER: The guideline development group (GDG) formulated 99 recommendations answering 31 key questions on the diagnosis and treatment of women with POI. WHAT IS KNOWN ALREADY: NA. STUDY DESIGN, SIZE, DURATION: This guideline was produced by a multidisciplinary group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to September 2014 and consensus within the guideline group on all recommendations. The GDG included a patient representative to ensure input from women with POI. After finalization of the draft, the European Society for Human Reproduction and Embryology (ESHRE) members and professional organizations were asked to review the guideline. PARTICIPANTS/MATERIALS, SETTING, METHODS: NA. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 17 recommendations on diagnosis and assessment of POI and 46 recommendations on the different sequelae of POI and their consequences for monitoring and treatment. Furthermore, 24 recommendations were formulated on hormone replacement therapy in women with POI, and two on alternative and complementary treatment. A chapter on puberty induction resulted in five recommendations. LIMITATIONS, REASONS FOR CAUTION: The main limitation of the guideline is that, due to the lack of data, many of the recommendations are based on expert opinion or indirect evidence from studies on post-menopausal women or women with Turner Syndrome. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limitations, the guideline group is confident that this document will be able to guide health care professionals in providing the best practice for managing women with POI given current evidence. Furthermore, the guideline group has formulated research recommendations on the gaps in knowledge identified in the literature searches, in an attempt to stimulate research on the key issues in POI. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the implementation of the guideline. The guideline group members did not receive payment. Dr Davies reports non-financial support from Novo Nordisk, outside the submitted work; the other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: NA.

Introduction of an interdisciplinary heart team-based transcatheter aortic valve implantation programme: short and mid-term outcomes.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been developed to treat symptomatic aortic stenosis in patients deemed too high risk for open-heart surgery. To address this complex population, an interdisciplinary heart team approach was proposed. AIM: Present the short- and mid-term outcomes of the first 100 patients in the Royal Prince Alfred Hospital multidisciplinary TAVI programme. METHODS: Single-centre registry. Baseline and procedural data were prospectively recorded. Outcomes were recorded according to Valve Academic Research Consortium - version 2 guidelines. RESULTS: All patients underwent a comprehensive interdisciplinary pre-procedural evaluation. Sixty-eight transfemoral and 32 transapical implantations were performed. Mean age was 82 (±8.9) years old with an average logistic EuroSCORE of 33. Although 13 procedures had major complications, there was no intraprocedural mortality. During the first month, 9% of patients were re-admitted due to heart failure and 13% had a permanent pacemaker implanted. A 3% 30-day and 8% follow-up (mean 17 months) mortalities were recorded. While no significant differences in the rate of complications were found between the first and second half of the experience, all cases of mortality within 30 days (n = 3) occurred in the initial half. Sustained haemodynamic results were obtained with TAVI (immediate mean aortic valve gradient reduction from 47 to 9 mmHg; 1-year echocardiographic gradient 9.9 mmHg, with no moderate or severe aortic regurgitation). CONCLUSION: Excellent results can be achieved with TAVI in very high-risk patients at an Australian institution. A comprehensive evaluation based on a heart team can overcome most of the difficulties imposed by this challenging population.

DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair.

Homologous recombination (HR) and nonhomologous end joining (NHEJ) are two distinct DNA double-stranded break (DSB) repair pathways. Here, we report that DNA-dependent protein kinase (DNA-PK), the core component of NHEJ, partnering with DNA-damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), regulates HR repair of DSBs. The regulation was accomplished through modulation of the p53 and replication protein A (RPA) interaction. We show that upon DNA damage, p53 and RPA were freed from a p53-RPA complex by simultaneous phosphorylations of RPA at the N-terminus of RPA32 subunit by DNA-PK and of p53 at Ser37 and Ser46 in a Chk1/Chk2-independent manner by ATR and ATM, respectively. Neither the phosphorylation of RPA nor of p53 alone could dissociate p53 and RPA. Furthermore, disruption of the release significantly compromised HR repair of DSBs. Our results reveal a mechanism for the crosstalk between HR repair and NHEJ through the co-regulation of p53-RPA interaction by DNA-PK, ATM and ATR.

A service evaluation of women attending the menopause/premature ovarian failure clinic of a tertiary referral centre.

This service evaluation aimed to characterise the referrals to the premature ovarian failure clinic, including the type of referral and patient needs, in order to plan for future service provision. The majority of women seen in the clinic experienced idiopathic premature ovarian failure, were aged 30-39 and were nulliparous at the time of diagnosis. Our service requires to be tailored to their needs. For many women, this includes a fertility consultation in the clinic and this part of the service is well used. Our data support the long-term follow-up of women both on treatment and those who initially decline treatment. Most women who initially decline treatment accept it after a few clinic visits. This may be due to consistent advice on the benefits of oestrogen treatment or due to yearly bone scans showing a change in bone density. There was a high non-attendance rate in this group: 21% of appointments were not attended.

Lupus anticoagulant, antiphospholipid syndrome and cardiac surgery.

The presence of lupus anticoagulant and the related condition antiphospholipid syndrome present a challenge in cardiac surgery where measured anticoagulation may not reflect the in vivo patient status of hypercoagulation. We report the successful management of a patient with lupus anticoagulant presenting for aortic valve replacement and coronary revascularisation. We used heparin for anticoagulation, specialised additional tests of anticoagulation and a reduced protamine dose. We also used tranexamic acid. The clinical problems with anticoagulation in patients with lupus anticoagulant include anticoagulant choice, measurement of adequate anticoagulation, antifibrinolytic usage, protamine dosing and blood product transfusion.

Ethical dilemmas related to counseling clients living with HIV/AIDS.

This study tested an eight-factor model of client actions/decisions in terms of the extent to which professionals counseling persons with HIV/AIDS believed that those actions/decisions presented ethical dilemmas, and the frequency with which they encountered such actions. A confirmatory factor analysis lent initial support for the hypothetical eight-factor ethical-dilemma model for the ratings regarding the extent to which the participants believed those items constituted ethical dilemmas. Similar results were obtained for the frequency ratings, but in this case a second, competing model was equally plausible. Several significant predictors of participant ratings were found and are discussed.

Perspective taking and theory of mind: do children predict interpretive diversity as a function of differences in observers' knowledge?

In 3 experiments, children's ability to vary their responses on perspective-taking tasks as a function of the other person's age was examined. In Experiment 1,4- and 5-year-olds were shown to be accurate in their judgments about the knowledge of a 6-month-old baby, a 4-year-old child, and an adult. In Experiment 2, 4-year-olds were asked to determine if a baby, child, and adult would be able to identify an object from a restricted view showing either an identifiable part, a small nondescript part, or no part of the object. Children tended to report that the observer would be able to identify the object from an identifiable or nondescript part. Their judgments were not affected by the age of the observer. Experiment 3 replicated the asymmetry in performance on the general knowledge task and the restricted view task and extended these results by testing 4-year-olds, 6-year-olds, and adults using a within-subjects design.

Landmark learning and visuo-spatial memories in gerbils.

The aim of this study is to understand what a rodent (Meriones unguiculatus) learns about the geometrical relations between a goal and nearby visual landmarks and how it uses this information to reach a goal. Gerbils were trained to find sunflower seeds on the floor of a light-tight, black painted room illuminated by a single light bulb hung from the ceiling. The position of the seed on the floor was specified by an array of one or more landmarks. Once training was complete, we recorded where the gerbils searched when landmarks were present but the seed was absent. In such tests, gerbils were confronted either with the array of landmarks to which they were accustomed or with a transformation of this array. Animals searched in the appropriate spot when trained to find seeds placed in a constant direction and at a constant distance from a single cylindrical landmark. Since gerbils look in one spot and not in a circle centred on the landmark, the direction between landmark and goal must be supplied by cues external to the landmark array. Distance, on the other hand, must be measured with respect to the landmark. Tests in which the size of the landmark was altered from that used in training suggest that distance is not learned solely in terms of the apparent size of the landmark as seen from the goal. Gerbils can still reach a goal defined by an array of landmarks when the room light is extinguished during their approach. This ability implies that they have already planned a trajectory to the goal before the room is darkened. In order to compute such a trajectory, their internal representation of landmarks and goal needs to contain information about the distances and bearings between landmarks and goal. For planning trajectories, each landmark of an array can be used separately from the others. Gerbils trained to a goal specified by an array of several landmarks were tested with one or more of the landmarks removed or with the array expanded. They then searched as though they had computed an independent trajectory for each landmark. For instance, gerbils trained with an array of two landmarks were tested with the distance between two landmarks doubled. The animals then searched for seeds in two positions, which were at the correct distance and in the right direction from each landmark.(ABSTRACT TRUNCATED AT 400 WORDS)

Ketoconazole's inhibition of fungal antigen-induced thymidine uptake by lymphocytes from patients with psoriasis.

Ketoconazole, an oral antifungal imidazole, has been effective in some refractory cases of psoriasis, particularly those with scalp involvement, perhaps because of suppression of Pityrosporum ovale. To assess an ancillary immunologically mediated role for ketoconazole, its effects were evaluated on psoriatic patients' lymphocyte function. Ketoconazole in vitro markedly inhibited Pityrosporum antigen-induced lymphocyte blastogenesis as indicated by impairment of cellular tritiated thymidine uptake. Ketoconazole likewise inhibited lymphocyte uptake of other pyrimidine nucleosides by both normal and psoriatic lymphocytes. Neither imidazole or an investigational triazole antifungal (Bay n7133) inhibited the uptake. Thus, ketoconazole potentially could affect psoriasis in seborrheic areas of skin by a direct antifungal action or indirectly by suppressing fungal antigen-induced lymphocyte-mediated immune responses affecting the skin.

Non-consultant peripheral clinics: a new approach to diabetic care.

A system of non-consultant peripheral clinics (NCPCs) established on the Isle of Wight is described. For the first phase of the study 182 diabetics attending the consultant clinic were allocated to the appropriate peripheral clinic (group 1). In the second phase, 152 new referrals were prospectively allocated between the consultant and appropriate peripheral clinics (group 2). Evaluation was made of the patients' random blood sugar and glycosylated haemoglobin. The savings in cost and time to patients resulted in over 90% of patients preferring the peripheral clinics. NCPCs are discussed in relation to hospital-based clinics and to other alternative systems of care. It is concluded that NCPCs could be incorporated into the diabetic service in other regions in the United Kingdom with advantages to diabetics and hospital services alike. These peripheral clinics are suited to all types of diabetics and perhaps the only clinical restriction is the desirability for metabolic deterioration to be managed by a consultant clinic until the patient is satisfactory.

Comparison of human versus porcine insulin in treatment of diabetes in children.

The blood glucose control obtained when using semi-synthetic monocomponent human insulin (insulin A) was compared with that using standard monocomponent porcine insulin (insulin B) in 14 children in a double blind crossover study. At the start of the study age, duration of diabetes, insulin dose, and daily carbohydrate intake were the same in both groups. After a one month run in period of standard treatment with porcine insulin the children were randomly divided into group 1 (three months of insulin A followed by three months of insulin B) and group 2 (three months of insulin B followed by three months of insulin A). During each treatment period blood glucose control was assessed by clinical symptoms, glycosylated haemoglobin, and home blood glucose monitoring. Although a significant difference in the period after lunch during 24 hour blood glucose profiles suggested a shorter onset time and faster peak action time of human insulin, no significant difference in the overall diabetic control was seen between the two types of insulin. There was a trend towards improved blood glucose control (irrespective of insulin) as the trial progressed. No clinical reactions to human insulin occurred, and there was no significant difference in the daily insulin dose between porcine and human insulin.

Comparison of ketoconazole and amphotericin B in interference with thymidine uptake by and blastogenesis of lymphocytes stimulated with Histoplasma capsulatum antigens.

Human peripheral blood lymphocytes stimulated with Histoplasma capsulatum yeasts were exposed in culture to graded concentrations of ketoconazole or amphotericin B and subsequently assessed for membrane integrity, thymidine uptake, and blastogenesis. Lymphocyte reactivity varied with concentration and duration of exposure to ketoconazole. Overt membrane toxicity resulted from exposure to 40 micrograms of ketoconazole per ml for 5 days, diminished thymidine uptake occurred with concentrations as low as 5 micrograms/ml, and 15 to 20 micrograms/ml caused a marked decrease in thymidine uptake and eventually diminished blastogenesis. The antilymphocyte action of ketoconazole was neutralized by increasing the concentration of human serum in cultures to 40% regardless of its cholesterol content. Amphotericin B activity was qualitatively similar but less pronounced.