Nurses\u27 Alumnae Association Bulletin, June 1966

President\u27s Message Officers and Committee Chairmen Financial Report Report to Alumnae Association Jefferson\u27s Development Program Report of the School of Nursing Student Activities Nursing Service Staff Association Resume of Alumnae Meetings Ways and Means Report Sick and Welfare Membership Private Duty Scholarship Building Fund Social Committee Class News Notice

StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR):Study protocol for a randomized controlled clinical trial

BACKGROUND: The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require. METHODS/DESIGN: STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat. DISCUSSION: The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878. Registered on 17 September 2014

Closed-loop insulin delivery during pregnancy complicated by type 1 diabetes.

OBJECTIVE: This study evaluated closed-loop insulin delivery with a model predictive control (MPC) algorithm during early (12-16 weeks) and late gestation (28-32 weeks) in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ten women with type 1 diabetes (age 31 years, diabetes duration 19 years, BMI 24.1 kg/m(2), booking A1C 6.9%) were studied over 24 h during early (14.8 weeks) and late pregnancy (28.0 weeks). A nurse adjusted the basal insulin infusion rate from continuous glucose measurements (CGM), fed into the MPC algorithm every 15 min. Mean glucose and time spent in target (63-140 mg/dL), hyperglycemic (>140 to ≥ 180 mg/dL), and hypoglycemic (140 mg/dL) was 7% (0-40%) in early and 0% (0-6%) in late pregnancy (P = 0.25) and hypoglycemic (<63 mg/dL) was 0% (0-3%) and 0% (0-0%), respectively (P = 0.18). Postprandial glucose control, glucose variability, insulin infusion rates, and CGM sensor accuracy were no different in early or late pregnancy. CONCLUSIONS: MPC algorithm performance was maintained throughout pregnancy, suggesting that overnight closed-loop insulin delivery could be used safely during pregnancy. More work is needed to achieve optimal postprandial glucose control.Diabetes UK (07/0003551), TCC (PDF/01/036), MRC (G0600717

Pharmacokinetics of insulin aspart in pump-treated subjects with type 1 diabetes: reproducibility and effect of age, weight, and duration of diabetes.

Insulin aspart, lispro, or glulisine are recommended in pump-treated type 1 diabetes (T1D). Aspart pharmacokinetics has been studied (1), but little is known about its reproducibility and associations with anthropometric and clinical factors. We analyzed retrospectively data collected in 70 pump-treated subjects with T1D, comprising 39 females, 46 young, with mean (SD) BMI 22.7 (4.2) kg/m2, A1C 8.1% (1.3) (65.3 [14.4] mmol/mol), and total daily insulin 0.8 (0.3) units/kg/day, who were undergoing investigations, with ethical approval, of closed-loop insulin delivery. Participants/guardians signed consent/assent as appropriate. Participants were admitted twice to the research facility, 1–6 weeks apart, for 15–37 h, and consumed 1–4 meals accompanied by prandial insulin aspart. Basal aspart was delivered using closed-loop insulin delivery or conventional pump therapy. Venous blood samples were collected every 30–60 min to measure plasma insulin (Invitron, Monmouth, U.K.). From 5,804 plasma insulin measurements, we estimated, using a two-compartment model, the time-to-peak plasma insulin concentration (tmax [min]), the metabolic clearance rate of insulin (MCR in mL/kg/min), and the background residual plasma insulin concentration (mU/L). Results are presented in Table 1. Sex differences in aspart kinetics were not observed. Aspart pharmacokinetics was weakly influenced by common clinical and anthropometric factors, because less than 20% of intersubject variability was explained by sex, BMI, total daily dose, A1C, and diabetes duration

The genome of Aeromonas salmonicida subsp. salmonicida A449: insights into the evolution of a fish pathogen

Background Aeromonas salmonicida subsp. salmonicida is a Gram-negative bacterium that is the causative agent of furunculosis, a bacterial septicaemia of salmonid fish. While other species of Aeromonas are opportunistic pathogens or are found in commensal or symbiotic relationships with animal hosts, A. salmonicida subsp. salmonicida causes disease in healthy fish. The genome sequence of A. salmonicida was determined to provide a better understanding of the virulence factors used by this pathogen to infect fish. Results The nucleotide sequences of the A. salmonicida subsp. salmonicida A449 chromosome and two large plasmids are characterized. The chromosome is 4,702,402 bp and encodes 4388 genes, while the two large plasmids are 166,749 and 155,098 bp with 178 and 164 genes, respectively. Notable features are a large inversion in the chromosome and, in one of the large plasmids, the presence of a Tn21 composite transposon containing mercury resistance genes and an In2 integron encoding genes for resistance to streptomycin/spectinomycin, quaternary ammonia compounds, sulphonamides and chloramphenicol. A large number of genes encoding potential virulence factors were identified; however, many appear to be pseudogenes since they contain insertion sequences, frameshifts or in-frame stop codons. A total of 170 pseudogenes and 88 insertion sequences (of ten different types) are found in the A. salmonicida genome. Comparison with the A. hydrophila ATCC 7966T genome reveals multiple large inversions in the chromosome as well as an approximately 9% difference in gene content indicating instances of single gene or operon loss or gain. A limited number of the pseudogenes found in A. salmonicida A449 were investigated in other Aeromonas strains and species. While nearly all the pseudogenes tested are present in A. salmonicida subsp. salmonicida strains, only about 25% were found in other A. salmonicida subspecies and none were detected in other Aeromonas species. Conclusion Relative to the A. hydrophila ATCC 7966T genome, the A. salmonicida subsp. salmonicida genome has acquired multiple mobile genetic elements, undergone substantial rearrangement and developed a significant number of pseudogenes. These changes appear to be a consequence of adaptation to a specific host, salmonid fish, and provide insights into the mechanisms used by the bacterium for infection and avoidance of host defence systems.Peer reviewed: YesNRC publication: Ye

Long-term dietary intervention trials: critical issues and challenges

Background: There are many challenges involved in running randomised controlled dietary intervention trials that investigate health outcomes. The aim of this paper was to evaluate the recruitment process, retention of participants and challenges faced in our dairy intervention trial, and to provide strategies to combat the difficulties of running long-term dietary intervention trials.Methods: A 12-month, randomised, two-way crossover study was conducted in overweight adults with habitually low dairy food consumption to assess the effects of a high dairy intake (4 servings of reduced-fat dairy per day) compared with a low dairy intake (1 serving of reduced-fat dairy per day) on measures of cardiometabolic and cognitive health. On completion of the high dairy intake phase, each participant was interviewed about their experience in the trial and responses were used to evaluate the key issues for study participants.Results: Although the recruitment target was achieved, high rates of attrition (49.3%) and difficulties maintaining participant compliance (reported by 37.8% of participants) were major threats to the viability of the study. Factors that contributed to the high attrition included inability to comply with the dietary requirements of the study protocol (27.0%), health problems or medication changes (24.3%) and time commitment (10.8%).Conclusion: Attrition and adherence to study requirements present challenges to trials requiring longer-term dietary change. Including a run-in period to further assess the motivation, commitment and availability of participants, maintaining regular contact with participants during control phases, minimising time commitment, providing flexibility with dietary requirements, facilitating positive experiences, and stringent monitoring of diet are some key recommendations for future dietary intervention trials.Trial registration: Australia and New Zealand Clinical Trials Registry (ACTRN 12608000538347)

Closed-loop basal insulin delivery over 36 hours in adolescents with type 1 diabetes: randomized clinical trial.

OBJECTIVE: We evaluated the safety and efficacy of closed-loop basal insulin delivery during sleep and after regular meals and unannounced periods of exercise. RESEARCH DESIGN AND METHODS: Twelve adolescents with type 1 diabetes (five males; mean age 15.0 [SD 1.4] years; HbA1c 7.9 [0.7]%; BMI 21.4 [2.6] kg/m(2)) were studied at a clinical research facility on two occasions and received, in random order, either closed-loop basal insulin delivery or conventional pump therapy for 36 h. During closed-loop insulin delivery, pump basal rates were adjusted every 15 min according to a model predictive control algorithm informed by subcutaneous sensor glucose levels. During control visits, subjects' standard infusion rates were applied. Prandial insulin boluses were given before main meals (50-80 g carbohydrates) but not before snacks (15-30 g carbohydrates). Subjects undertook moderate-intensity exercise, not announced to the algorithm, on a stationary bicycle at a 140 bpm heart rate in the morning (40 min) and afternoon (20 min). Primary outcome was time when plasma glucose was in the target range (71-180 mg/dL). RESULTS: Closed-loop basal insulin delivery increased percentage time when glucose was in the target range (median 84% [interquartile range 78-88%] vs. 49% [26-79%], P = 0.02) and reduced mean plasma glucose levels (128 [19] vs. 165 [55] mg/dL, P = 0.02). Plasma glucose levels were in the target range 100% of the time on 17 of 24 nights during closed-loop insulin delivery. Hypoglycemia occurred on 10 occasions during control visits and 9 occasions during closed-loop delivery (5 episodes were exercise related, and 4 occurred within 2.5 h of prandial bolus). CONCLUSIONS: Day-and-night closed-loop basal insulin delivery can improve glucose control in adolescents. However, unannounced moderate-intensity exercise and excessive prandial boluses pose challenges to hypoglycemia-free closed-loop basal insulin delivery

Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial.

OBJECTIVE: To evaluate feasibility, safety, and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Overnight closed loop was evaluated at home by 16 pump-treated adolescents with type 1 diabetes aged 12-18 years. Over a 3-week period, overnight insulin delivery was directed by a closed-loop system, and on another 3-week period sensor-augmented therapy was applied. The order of interventions was random. The primary end point was time when adjusted sensor glucose was between 3.9 and 8.0 mmol/L from 2300 to 0700 h. RESULTS: Closed loop was constantly applied over at least 4 h on 269 nights (80%); sensor data were collected over at least 4 h on 282 control nights (84%). Closed loop increased time spent with glucose in target by a median 15% (interquartile range -9 to 43; P < 0.001). Mean overnight glucose was reduced by a mean 14 (SD 58) mg/dL (P < 0.001). Time when glucose was <70 mg/dL was low in both groups, but nights with glucose <63 mg/dL for at least 20 min were less frequent during closed loop (10 vs. 17%; P = 0.01). Despite lower total daily insulin doses by a median 2.3 (interquartile range -4.7 to 9.3) units (P = 0.009), overall 24-h glucose was reduced by a mean 9 (SD 41) mg/dL (P = 0.006) during closed loop. CONCLUSIONS: Unsupervised home use of overnight closed loop in adolescents with type 1 diabetes is safe and feasible. Glucose control was improved during the day and night with fewer episodes of nocturnal hypoglycemia.Supported by Juvenile Diabetes Research Foundation (#22-2006-1113, #22-2007-1801, #22-2009-801, #22-2009-802), Diabetes UK (BDA07/0003549), National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621), Medical Research Council Centre for Obesity and Related metabolic Diseases, and National Institute for Health Research Cambridge Biomedical Research Centre. Abbott Diabetes Care supplied continuous glucose delivery devices and sensors and modified devices to facilitate real-time connectivity.This is the final published version, also available from the American Diabetes Association at http://care.diabetesjournals.org/content/37/5/1204

Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies

Objective To compare the safety and efficacy of overnight closed loop delivery of insulin (artificial pancreas) with conventional insulin pump therapy in adults with type 1 diabetes