EffEctiveness of Prophylactic fOam dressings in the prevention of saCral pressure injuries in at-risk hospitalised patients: the EEPOC trial.

BACKGROUND: Prophylactic dressings are increasingly used to prevent pressure injuries in hospitalised patients. However, evidence regarding the effectiveness of these dressings is still emerging. This trial aims to determine the clinical and cost-effectiveness of a prophylactic silicone foam border dressing in preventing sacral pressure injuries in medical-surgical patients. METHODS: This is a multicentre, pragmatic, parallel group, randomised controlled trial. A sample size of 1320 was calculated to have >90% power to detect a 5% difference in the primary outcome at an alpha of 0.05. Adult patients admitted to participating medical-surgical wards are screened for eligibility: ≥18 years, admitted to hospital within the previous 36 h, expected length of stay of ≥24 h, and assessed high risk for hospital-acquired pressure injury. Consenting participants are randomly allocated to either prophylactic silicone foam dressing intervention or usual care without any dressing as the control group via a web-based randomisation service independent of the trial. Patients are enrolled across three Australian hospitals. The primary outcome is the cumulative incidence of patients who develop a sacral pressure injury. Secondary outcomes include the time to sacral pressure injury, incidence of severity (stage) of sacral pressure injury, cost-effectiveness of dressings, and process evaluation. Participant outcomes are assessed daily for up to 14 days by blinded independent outcome assessors using de-identified, digitally modified sacral photographs. Those who develop a sacral pressure injury are followed for an additional 14 days to estimate costs of pressure injury treatment. Analysis of clinical outcomes will be based on intention-to-treat, per-protocol, and sensitivity analyses. DISCUSSION: This trial aims to provide definitive evidence on the effect prophylactic dressings have on the development of hospital-acquired sacral pressure injuries in medical-surgical patients. A parallel economic evaluation of pressure injury prevention and treatment will enable evidence-informed decisions and policy. The inclusion of a process evaluation will help to explain the contextual factors that may have a bearing on trial results including the acceptability of the dressings to patients and staff. The trial commenced 5 March 2020 and has been significantly delayed due to COVID-19. TRIAL REGISTRATION: ANZCTR ACTRN12619000763145. Prospectively registered on 22 May 2019.

Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep.

The prenatal diet can program an individual's cardiovascular system towards later higher resting blood pressure and kidney dysfunction, but the extent to which these programmed responses are directly determined by the timing of maternal nutritional manipulation is unknown. In the present study we examined whether maternal nutrient restriction targeted over the period of maximal placental growth, i.e. days 28-80 of gestation, resulted in altered blood pressure or kidney development in the juvenile offspring. This was undertaken in 6-month-old sheep born to mothers fed control (100-150 % of the recommended metabolisable energy (ME) intake for that stage of gestation) or nutrient-restricted (NR; 50 % ME; n 6) diets between days 28 and 80 of gestation. Controls were additionally grouped according to normal (>3, n 7) or low body condition score (LBCS; <2, n 6), thereby enabling us to examine the effect of maternal body composition on later cardiovascular function. From day 80 to term (approximately 147 d) all sheep were fed to 100 % ME. Offspring were weaned at 12 weeks and pasture-reared until 6 months of age when cardiovascular function was determined. Both LBCS and NR sheep tended to have lower resting systolic (control, 85 (se 2); LBCS, 77 (se 3); NR, 77 (se 3) mmHg) and diastolic blood pressure relative to controls. Total nephron count was markedly lower in both LBCS and NR relative to controls (LBCS, 59 (se 6); NR, 56 (se 12) %). Our data suggest that maternal body composition around conception is as important as the level of nutrient intake during early pregnancy in programming later cardiovascular health.

Description of a technique for anaesthetizing pregnant ewes for fetal surgery.

General anaesthesia in 12 pregnant ewes undergoing surgery for fetal physiological research was supplemented with an intravenous infusion of remifentanil. This allowed us to employ a lighter plane of surgical anaesthesia and to use intermittent positive pressure ventilation. Our aim was to improve fetomaternal outcome. We monitored maternal pulse, blood pressure, transcutaneous oxygen saturation and end-tidal carbon dioxide levels. Remifentanil doses of 0.75-2.0 microg/kg/min were needed and typically this allowed halothane concentrations of 1-1.5% to be used for maintenance of anaesthesia. Surgery lasted up to 2.5 h. All 12 ewes and their singleton fetuses survived the peri- and postoperative period in good condition.

Resumption of follicle growth in gilts after ovarian autografting.

The aims of the study were to evaluate autografting of porcine ovarian tissue in terms of establishment of a blood supply, follicle survival and development, commencement of oestrous cycles and endocrine patterns in this polyovular species. Experiment 1, a preliminary study on four gilts, showed that ovarian tissue slices survived the grafting procedure and re-vascularised. In Experiment 2, a further six pre-pubertal gilts had both ovaries surgically removed and two thin cortical slices of each ovary were immediately reattached to each of the ovarian pedicles. Blood samples were taken at surgery and then weekly. Two gilts were slaughtered 2 weeks after surgery and ovarian tissue recovered. The remaining four gilts underwent daily checks for behavioural oestrus until slaughter 24 weeks after surgery. All four gilts showed standing heat at least once prior to slaughter. Plasma LH and FSH concentrations increased significantly (P<0.01) by 3 days after surgery, then fell gradually, but did not return to pre-surgery levels. Progesterone concentrations showed some evidence of cyclicity in all animals. In the grafted tissue, re-vascularisation of the tissue was apparent by 2 weeks post-grafting, although no preantral or antral follicles were observed. The tissue recovered after 24 weeks contained healthy preantral and antral follicles, luteal tissue and some large cystic follicles. It is unclear whether these cysts were the result of ovarian or hypothalamic/pituitary disturbance. In conclusion, the results of this study have shown that follicle growth and resumption of cyclicity can be achieved following ovarian autografting in pigs and indicate that this will be a useful model for investigating the mechanisms that control the early stages of follicular growth and ultimately ovulation rate in this multiovular species.

Programming of adult cardiovascular function after early maternal undernutrition in sheep.

The prenatal nutritional environment influences the subsequent risk of hypertension in adulthood. Animal studies have used, generally, the rat as a model species to illustrate the association between maternal nutrient intake and blood pressure in the resulting adult offspring. No study to date has shown programming of adult cardiovascular function in the sheep through maternal dietary intervention. We therefore fed pregnant sheep to either 100% recommended intake from day 0 of gestation to term [ approximately 147 days gestational age (dGA); controls n = 8] or to 50% recommended intake from day 0 to 95 dGA and thereafter to 100% intake (NR; n = 9). Sheep lambed naturally, offspring were weaned at 16 wk, and the male offspring were reared on pasture until 3 yr of age. At this time, cardiovascular catheters were inserted under halothane anesthesia and sheep were allowed 2-4 days recovery. Basal cardiovascular status and pressor responses to infusion of norepinephrine, angiotensin II, and captopril were then assessed alongside basal plasma concentrations of glucose, cortisol, and leptin. NR sheep were of similar birth weight to controls but at 3 yr of age had higher blood pressure before, but not after, feeding. Peripheral sensitivity to vasoconstrictor infusion was similar between dietary groups, although a reflex bradycardia was not apparent in NR sheep during norepinephrine infusion. Circulating leptin correlated well with fat mass and increased more after vasoconstrictor infusion in NR sheep. In conclusion, early NR has been shown to program aspects of cardiovascular control and adipocyte function in adult sheep.

The effects of overnight fasting, feeding, or sucrose supplementation prior to necropsy in rats.

This study was designed to investigate the acute effects on routine hematology, serum biochemistry, gastrointestinal contents and weight, and liver weight and morphology due to overnight sucrose feeding of rats prior to necropsy. Groups of rats (five males and five females/group) were fasted overnight, fed chow, or fed sucrose and were euthanized approximately 17 h later. At necropsy, blood was obtained for hematology and serum biochemistry profiling, and the livers and gastrointestinal tracts were weighed and examined. The livers also were evaluated microscopically. The blood glucose and urea nitrogen concentrations and liver weights of animals fed sucrose differed significantly from those of the other groups. Alterations were more striking in males than females. Marked histological changes were present in livers from animals fed sucrose prior to necropsy compared with fasted or chow-fed animals, and these changes were attributed to increased glycogen deposition in the sucrose-fed animals. Because of alterations in hepatic structure and function, we cannot recommend the practice of feeding sucrose to rats prior to necropsy for toxicology studies or any studies examining hepatic function.

Physician-assisted suicide: the legal slippery slope.

BACKGROUND: In Oregon, physicians can prescribe lethal amounts of medication only if requested by competent, terminally ill patients. However, the possibility of extending the practice to patients who lack decisional capacity exists. This paper examines why the legal extension of physician-assisted suicide (PAS) to incapacitated patients is possible, and perhaps likely. METHODS: The author reviews several pivotal court cases that have served to define the distinctions and legalities among "right-to-die" cases and the various forms of euthanasia and PAS. RESULTS: Significant public support exists for legalizing PAS and voluntary euthanasia in the United States. The only defenses against sliding from PAS to voluntary euthanasia are adhering to traditional physician morality that stands against it and keeping the issue of voluntary euthanasia legally framed as homicide. However, if voluntary euthanasia evolves euphemistically as a medical choice issue, then the possibility of its legalization exists. CONCLUSIONS: If courts allow PAS to be framed as a basic personal right akin to the right to refuse treatment, and if they rely on right-to-die case precedents, then they will likely extend PAS to voluntary euthanasia and nonvoluntary euthanasia. This would be done by extending the right to PAS to incapacitated patients, who may or may not have expressed a choice for PAS prior to incapacity.

Pressure flow study data in a group of asymptomatic male control patients 45 years old or older.

PURPOSE: The role of pressure flow studies in the routine evaluation of patients with benign prostatic hyperplasia remains a controversial issue in urological practice. There are little data on age matched asymptomatic control groups. We evaluated pressure flow findings in such a group. MATERIALS AND METHODS: A total of 24 male patients 47 to 80 years old (mean age 62.5) attending a general surgical clinic were recruited for study after ethical committee approval. The volunteers had never sought medical attention for urinary symptoms and did not perceive themselves as having a urological problem. Volunteers were assessed by International Prostate Symptom Score (I-PSS) and Madsen symptom score, clinical examination, free uroflowmetry, post-void residual ultrasound, repeat pressure flow studies and transrectal ultrasonography. Pressure flow tracings were manually analyzed for standard urodynamic values and the degree of bladder outflow obstruction according to recognized International Continence Society, Abrams-Griffith nomogram, linear passive urethral resistance relation and urethral resistance factor classifications. RESULTS: Median I-PSS was 2.0 (interquartile range 1.2 to 5.7). For I-PSS quality of life the median was 1.0 (interquartile range 0.75 to 2.0). On pressure flow studies 3 patients (13%) had unequivocal obstruction, 7 (29%) were in the equivocal area and 14 (58%) had no obstruction, while 15 (63%) had unstable contractions on medium fill cystometry. CONCLUSIONS: The data show that a surprising number of apparently normal men are obstructed by commonly used criteria. This finding confirms asymptomatic obstruction, suggesting that obstruction may be less important in the development of symptoms than previously thought. Also, until the natural history of obstruction is more clearly defined surgery in obstructed asymptomatic patients is probably unwise.

The in vitro activity of ABT773, a new ketolide antimicrobial agent.

The in vitro activity of ABT773, a ketolide antimicrobial agent, was investigated and compared with those of seven other antibiotics. Type strains and 733 Gram-positive, Gram-negative and anaerobic isolates of clinical origin and four CHLAMYDIA: isolates were used. The activity of ABT773 was very similar to that of telithromycin, the other ketolide tested. The MIC(90) was < or = 0.5 mg/L for all bacteria examined except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae and BACTEROIDES: spp. The antichlamydial activity of ABT773 was greater than that of telithromycin, erythromycin and ciprofloxacin. Neither an increase in the size of the inoculm nor the addition of human serum had any marked affect on the in vitro activity of ABT773.

Histologic findings in persistent hyperinsulinemic hypoglycemia of infancy: Australian experience.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by hyperinsulinism and profound hypoglycemia, with most children requiring pancreatic resection. The histological classification of PHHI is controversial. Most authors acknowledge the existence of focal areas of islet cell proliferation (adenomatosis) in 30%-50% of cases and a diffuse disorganisation of islet architecture, termed "nesidiodysplasia," in others. De Lonlay et al. reported that cases with adenomatosis are focal with normal remainder of pancreas and that focal and diffuse disease can be differentiated intraoperatively, on the basis of increased beta-cell nuclear size found only in the diffusely abnormal pancreas. We have examined pancreatic histology in a blinded controlled study of PHHI patients. Pancreatic tissue was obtained at autopsy from 60 normal subjects (age 17 weeks gestation to 76 years) and from surgical specimens of 31 PHHI patients. Sections from PHHI subjects (n = 294 blocks) and control sections were stained with hematoxylin and eosin, insulin, glucagon, somatostatin, NSE, cytokeratin 19, and vimentin. Three sections from each PHHI patient were randomly chosen for further analysis. Age-matched control (n = 34) and PHHI sections (n = 66) were examined, with the identity of subjects concealed. A diagnosis of normal histology, adenomatosis, or diffuse nesidiodysplasia was recorded for each section. The presence of large beta-cell nuclei (>19 microm), ductuloinsular complexes, and centroacinar cell proliferation was noted. Of a total of 65 subjects examined (34 control and 31 PHHI), 37 subjects were identified as normal on both sections examined. All the control cases were correctly identified as normal and none had large beta-cell nuclei or centroacinar cell proliferation. Of 31 PHHI patients, 28 were identified as abnormal, either on the basis of abnormal architecture and/or abnormally large beta-cell nuclei. Three patients were identified as normal in both sections. Fifteen of 31 patients had diffuse nesidiodysplasia only. Of 13 patients with areas of adenomatosis, 2 had resection of a nodule with adenomatosis present in most of the tissue removed at surgery. Nine patients had a diagnosis of adenomatosis in one section and a diagnosis of diffuse nesidiodysplasia in the other sections from nonadjacent pancreas. Only 2 of 31 PHHI cases had adenomatosis on one section examined and normal pancreas on the other section examined. Large beta-cell nuclei were variably found in PHHI sections. Only 5 of 15 patients with diffuse nesidiodysplasia had large nuclei in both sections examined. Centroacinar cell proliferation was identified in 12 PHHI subjects, 6 with adenomatosis and diffuse nesidiodysplasia and 6 with diffuse changes only. It was patchy in distribution within sections and present in only one section in 7 of the 12 subjects. In summary, we have shown that a blinded observer could differentiate control and PHHI pancreatic tissue. Only 2 of 31 patients (6%) had focal adenomatosis with normal nonadjacent pancreas, the majority (24 of 31) had diffuse nesidiodysplasia affecting the remainder of their pancreas, with 38% (9 of 24) also having areas of adenomatosis. Large beta-cell nuclei did not reliably identify those with diffuse disease in this study. There was evidence of significant ductal and centroacinar proliferation in 39% of PHHI cases, which was not observed in any of the controls. We have shown that PHHI subjects have a spectrum of pancreatic histological abnormalities, from no abnormality to diffuse subtle changes to florid adenomatosis. Patients could not be segregated into subtypes for different operative intervention despite the availability of full immunohistochemical staining.

Deactivating the implantable cardioverter-defibrillator: a biofixture analysis.

Automatic implantable cardioverter-defibrillators (ICDs) are becoming increasingly common, as is refusal of resuscitative efforts at the end of life, both by patients and surrogate decision-makers. While it is clear that a terminally ill patient who lacks decisional capacity may, through a surrogate, refuse cardiopulmonary resuscitation (CPR), is it appropriate for physicians to infer from such a refusal that the patient's ICD should be deactivated? A proper answer to this question requires consideration of the nature of consent to a do-not-resuscitate (DNR) order, the context in which permission is given for the writing of the DNR order, and the ontologic status of implantable devices in general and ICDs in particular. We introduce the concept of "biofixtures" and suggest that a biofixture analysis is a novel way of approaching the difficult ethical issues that may confound the care of patients with implantable devices.

Efficacy of sperm mobility assessment in commercial flocks and the relationships of sperm mobility and insemination dose with fertility in turkeys.

Our objectives were to evaluate: 1) the efficacy of the Sperm Mobility Test on commercial turkey farms, and 2) the influence of sperm mobility phenotype on fertility when insemination parameters are varied. In research flocks, differences in sperm mobility among toms are predictive of fertility. We wanted to test the efficacy of this sire selection test in practical, real-world situations, evaluating its usefulness in terms of assessing large numbers of toms, different strains of turkeys, and variable management practices. Utilizing field study results, controlled studies were then conducted to improve test parameters. For the field trials, semen from each of 405 breeder toms (11 strains or lines) was evaluated either in duplicate (n = 285) or in triplicate (n = 120). Sperm mobility was normally distributed among all toms tested, except for one strain. Because the sperm mobility indices for toms evaluated in these field trials were higher than those observed in research flocks, the Sperm Mobility Test was modified to increase the separation between high and low sperm mobility phenotypes by increasing the concentration of Accudenz. To determine the effects of sperm mobility and insemination dose on sustained fertility through time, hens from a research flock were inseminated twice before the onset of lay with sperm from toms classified as high-, average-, or low-mobility in concentrations of 25 to 400 million sperm per artificial insemination dose, and egg fertility was evaluated over a 5-wk period. Toms with the high-mobility sperm phenotype maintained higher fertility (P < 0.05) over the 5-wk period at all insemination doses compared with toms with low-mobility sperm. Toms with high-mobility sperm sired equal numbers of poults in a sperm competition study in which numbers favored low-mobility toms by 3:1. These results demonstrate that the Sperm Mobility Test can be used for on-farm evaluation of semen quality of toms in commercial flocks and that sperm mobility influences fertility and sire fitness.

Absence of correlation between telomerase activity and hepatic neoplasia in B6C3F1 mice.

Telomeres are the physical ends of eukaryotic chromosomes, which maintain chromosome stability and are progressively shortened with aging in somatic cells. The enzyme telomerase elongates telometric DNA and while not usually detectable in human somatic cells is expressed in most human tumors. The present study was conducted to determine if telomerase activity is a marker for spontaneous hepatic neoplastic changes in B6C3F1 mice, a strain frequently used in rodent carcinogenicity studies. Telomerase activity was generally higher in microscopically normal liver tissue from 8-week-old compared to aged mice (110-week-old); however, telomerase activity was not consistently increased in hepatocellular adenomas and carcinomas. It is proposed that, while elevated telomerase activity may modulate human tumor development, modulation of telomerase activity is not a feature of hepatic tumors in B6C3F1 mice and therefore is unlikely to have utility as a molecular marker for hepatic neoplasia in this mouse strain.

Probabilistic approach to the establishment of maximal content limits of impurities in drug formulations: the case of parenteral diphenylhydantoic acid.

Diphenylhydantoic acid (DPHA) is a degradation product in parenteral formulations of the anticonvulsant phenytoin and the prodrug fosphenytoin. DPHA has also been reported to be a minor metabolite of phenytoin. Levels found in the urine of various species, including humans, after oral or intravenous (iv) phenytoin ranged from undetected to a few percent of administered dose. In the present analysis, the toxicologic profile of DPHA was integrated with exposure data in order to characterize its safety under recommended clinical regimens of fosphenytoin administration. In preclinical safety studies, DPHA was without effect in the Ames assay and at concentrations up to 3000 microg/plate in the presence or absence of metabolic activation, and in the in vitro micronucleus test with acute and 2-week repeated dose studies in Wistar rats at iv doses up to 15 mg/kg. In 4-week studies conducted in rats and dogs receiving fosphenytoin containing DPHA levels up to 1.1%, and in an in vitro structural chromosome aberration test with DPHA levels up to 2.0%, all findings were consistent with known effects of phenytoin (such as CNS signs and increased liver weight), and none were attributed to DPHA. Reports in the literature indicate that in murine in vivo and in vitro models, DPHA has much lower potential for reproductive toxicity than phenytoin. A no-observed-effect level (NOEL) of 15 mg/kg established from the 2-week study in rats was used with probabilistic techniques to estimate tolerable daily doses (TDDs) of DPHA. In this approach, interspecies correction was performed by allometrically scaling the NOEL based on a distributional power of body weight while intraindividual variability was accounted for by selecting the lower percentiles of the population-based distribution of TDDs. The results indicate that a DPHA content limit of 3.0% in an administered dose of fosphenytoin is unlikely to cause adverse effects in patients.