Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

Support for a rare pattern of temperature-dependent sex determination in archaic reptiles: evidence from two species of tuatara (Sphenodon)

<p>Abstract</p> <p>Background</p> <p>The sex of many reptiles is determined by the temperature an embryo experiences during its development. Three patterns of temperature-dependent sex determination (TSD) have been defined, but one pattern where only males are produced above an upper temperature threshold (Type IB) is controversial. Here we report new data on the relationship between constant temperature incubation and sexual phenotype in two species of tuatara (<it>Sphenodon</it>), archaic reptiles of enormous zoological significance as the sole representatives of a once widespread reptilian order.</p> <p>Results</p> <p>In both species, the pattern observed with constant incubation temperatures from 18 to 23°C (or 24°C) supported a female→male (FM or Type IB) pattern of TSD: in <it>Sphenodon guntheri </it>males were produced above a pivotal temperature of 21.6°C, and in <it>S. punctatus </it>(unnamed subspecies on Stephens Island, Cook Strait), males were produced above a pivotal temperature of 22.0°C. The pivotal temperatures and scaling parameters differed between species (p < 0.001). The thermosensitive period (TSP), where temperature influences gonad morphogenesis, occurs between 0.25 and 0.55 of embryonic development. While it is possible that the more common female→male→female (FMF or Type II) pattern exists, with a second pivotal temperature above 23–24°C, we review several lines of evidence to the contrary. Most notably, we show that in <it>S. punctatus</it>, the warmest natural nests during the TSP produce predominantly males.</p> <p>Conclusion</p> <p>An FM pattern of TSD could be currently adaptive in promoting sexual size dimorphism in tuatara. However, an FM pattern has particularly serious consequences for <it>S. guntheri </it>because current patterns of global warming could exacerbate the male bias already present in the relic population.</p

Relationship Between Hemodynamically Significant Ductus Arteriosus and Ischemia-Modified Albumin in Premature Infants

Hemodynamically significant ductus arteriosus (hsPDA) may alter organ perfusion by interfering blood flow to the tissues. Therefore, in infants with hsPDA, hypoxia occurs in many tissues. In this study, we aimed to investigate the diagnostic significance of serum (ischemia-modified albumin) IMA levels as a screening tool for hsPDA, and its relation to the severity of the disease in the preterm neonates. For this purpose, seventy-two premature infants with gestation age <34 weeks were included in the study. Thirty premature infants with hsPDA were assigned as the study group and 42 premature infants without PDA were determined as the control group. Blood samples were collected before the treatment and 24 h after the treatment, and analyzed for IMA levels. IMA levels in the study group (1.26 ± 0.36 ABSU) were found to be significantly higher than control group (0.65 ± 0.12 ABSU) (p < 0.05). In infants with hsPDA, a positive correlation was found between IMA and PDA diameter (ρ = 0.876, p = 0.022), and LA/Ao ratio (ρ = 0.863, p = 0.014). The cut-off value of IMA for hsPDA was measured as 0.78 ABSU with 88.89 % sensitivity, and 90.24 % specificity, 85.71 % positive predictive, 92.5 % negative predictive value [area under the curve (AUC) = 0.96; p < 0.001]. The mean IMA value of the infants with hsPDA before treatment was 1.26 ± 0.36 ABSU, and the mean IMA value of infants after medical treatment was 0.67 ± 0.27 ABSU (p = 0.03). We concluded that IMA can be used as a marker for the diagnosis and monitoring of a successful treatment of hsPDA

Plasma exosomes characterization reveals a perioperative protein signature in older patients undergoing different types of on-pump cardiac surgery

Although exosomes are extracellular nanovesicles mainly involved in cardioprotection, it is not known whether plasma exosomes of older patients undergoing different types of on-pump cardiac surgery protect cardiomyocytes from apoptosis. Since different exosomal proteins confer pro-survival effects, we have analyzed the protein cargo of exosomes circulating early after aortic unclamping. Plasma exosomes and serum cardiac troponin I levels were measured in older cardiac surgery patients (NYHA II-III) who underwent first-time on-pump coronary artery bypass graft (CABG; n = 15) or minimally invasive heart valve surgery (mitral valve repair, n = 15; aortic valve replacement, n = 15) at induction of anesthesia (T0, baseline), 3 h (T1) and 72 h (T2) after aortic unclamping. Anti-apoptotic role of exosomes was assessed in HL-1 cardiomyocytes exposed to hypoxia/re-oxygenation (H/R) by TUNEL assay. Protein exosomal cargo was characterized by mass spectrometry approach. Exosome levels increased at T1 (P &lt; 0.01) in accord with troponin values in all groups. In CABG group, plasma exosomes further increased at T2 (P &lt; 0.01) whereas troponin levels decreased. In vitro, all T1-exosomes prevented H/R-induced apoptosis. A total of 340 exosomal proteins were identified in all groups, yet 10% of those proteins were unique for each surgery type. In particular, 22 and 12 pro-survival proteins were detected in T1-exosomes of heart valve surgery and CABG patients, respectively. Our results suggest that endogenous intraoperative cardioprotection in older cardiac surgery patients is early mediated by distinct exosomal proteins regardless of surgery type