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The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Balloon aortic valvuloplasty and open surgical valvotomy are procedures to treat neonatal aortic stenosis, and there is controversy as to which method has superior outcomes.
We reviewed the records of patients at our institution since 2000 who had a balloon aortic valvuloplasty or surgical valvotomy via an open commissurotomy prior to 2 months of age.
Forty patients had balloon aortic valvuloplasty and 15 patients had surgical valvotomy via an open commissurotomy. There was no difference in post-procedure mean gradient by transthoracic echocardiogram, which were 25.8 mmHg for balloon aortic valvuloplasty and 26.2 mmHg for surgical valvotomy, p = 0.87. Post-procedure, 15% of balloon aortic valvuloplasty patients had moderate aortic insufficiency and 2.5% of patients had severe aortic insufficiency, while no surgical valvotomy patients had moderate or severe aortic insufficiency. The average number of post-procedure hospital days was 14.2 for balloon aortic valvuloplasty and 19.8 for surgical valvotomy (p = 0.52). Freedom from re-intervention was 69% for balloon aortic valvuloplasty and 67% for surgical valvotomy at 1 year, and 43% for balloon aortic valvuloplasty and 67% for surgical valvotomy at 5 years (p = 0.60).
Balloon aortic valvuloplasty and surgical valvotomy provide similar short-term reduction in valve gradient. Balloon aortic valvuloplasty has a slightly shorter but not statistically significant hospital stay. Freedom from re-intervention is similar at 1 year. At 5 years, it is slightly higher in surgical valvotomy, though not statistically different. Balloon aortic valvuloplasty had a higher incidence of significant aortic insufficiency. Long-term comparisons cannot be made given the lack of long-term follow-up with surgical valvotomy.
The Ross procedure involves using the native pulmonary valve for aortic valve replacement then replacing the pulmonary valve with an allograft or xenograft. We aimed to compare our age-matched experience with the bovine jugular vein conduit and the pulmonary homograft for pulmonary valve replacement during the Ross procedure in children.
Between 1998 and 2016, 15 patients <18 years of age underwent a Ross procedure using the bovine jugular vein conduit (Ross-Bovine Jugular Vein Conduit) at our institution. These patients were age-matched with 15 patients who had the Ross operation with a standard pulmonary homograft for right ventricular outflow tract reconstruction (Ross-Pulmonary Homograft). Paper and electronic medical records were retrospectively reviewed.
The median age of the Ross-Bovine Jugular Vein Conduit and Ross-Pulmonary Homograft patients were 4.8 years (interquartile range 1.1–6.6) and 3.3 years (interquartile 1.2–7.6), respectively (p = 0.6). The median follow-up time for the Ross-Bovine Jugular Vein Conduit and Ross-Pulmonary Homograft groups were 1.7 years (interquartile range 0.5–4.9) and 6.8 years (interquartile range 1.9–13.4), respectively (p = 0.03). Overall, 5-year survival, freedom from redo aortic valve replacement, and freedom from pulmonary valve replacement were similar between groups.
The bovine jugular vein conduit and pulmonary homograft have favourable mid-term durability when used for right ventricular outflow tract reconstruction for the Ross operation. The bovine jugular vein conduit may be a suitable replacement for appropriately sized patients undergoing a Ross aortic valve replacement, though longer follow-up is needed.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
In this article, I will outline the origin of cardiothoracic surgical (CTS) training at Indiana University (IU) and its evolution to the present. I will describe my educational background, surgical training in this specialty, and my role as an educator of CT surgeons. I will describe our faculty and the structure of the CTS residency. Finally, I will describe a newly adopted smart phone “App” called SIMPL, which allows the resident and faculty to quickly (<4 minutes) evaluate the CTS resident’s performance for each surgical case they perform together. The tool prompts both parties to determine the resident’s level of involvement in >50% of the most critical aspects of each surgical procedure, the resident’s performance during the critical portion of the operation from poor to excellent, and the degree of difficulty of the operation from simple to complex. The attending surgeon and the resident data are then forwarded to the SIMPL database where the SIMPL software aggregates data for each resident and procedure producing a report at the end of the rotation of the resident’s performance relative to his peers. This additional evaluation process will better ensure that our CTS residents are “practice ready” when they complete their training.
There currently is considerable confusion regarding the correct application of the name Choristoneura occidentalis Freeman (Lepidoptera: Tortricidae). This name has historically been applied to the western spruce budworm, a serious forest pest in western North America. However, in 2008 Razowski transferred the African species Archips occidentalis (Walsingham) to Choristoneura Lederer and proposed C. freemani Razowski as a replacement name for the western spruce budworm. The validity of these nomenclatural changes and alternative solutions to resolve the confusion they have caused are discussed. Illustrations of wing patterns and genitalia for the two species are provided.
Despite the recent rapid decline of many grassland bird species, the relative importance of habitat configuration to population persistence is unclear. We used Southeastern American Kestrels Falco sparverius paulus in north-central Florida as a model system to explore the relative influence of landscape structure components on site occupancy patterns at two spatial scales, and for two different time periods. We focused on the dynamic processes of site-level population expansion or contraction. We modelled the occupancy of 131 American Kestrel nest boxes with Bayesian state-space dynamic occupancy models that considered both the partially observed process of true occupancy and the probability of detection of occupancy. We used reversible jump Markov chain Monte Carlo (RJMCMC) algorithms to identify variables that described the continued occupancy of nest boxes, or ϕ, and the probability of colonisation of nest boxes between time periods, or γ3. Changes in open habitat patch isolation at a fine scale, as estimated by the variability of nearest neighbour distance, predicted site colonisation between decades, and patch shape variability was related to ϕ during the early time period (1992–93). We found no strong effects of landscape structure on ϕ during the later time period (2008–2010). We also found no evidence for effects of loss of open habitat on box occupancy or colonization. Our results indicate that continued habitat fragmentation would be deleterious for this threatened subspecies. Additionally, certain land cover management practices recommended for the Florida sandhills, such as frequent low-intensity controlled burns, will likely help conservation attempts.
Imidazoles present a tunable, versatile and economical platform for the development of novel liquid solvents and polymer membranes for CO2 capture. An overview of our studies in this area is presented, with emphasis on characterization of structure-property relationships in imidazole-based materials through both experimental and computational studies. To this end, a growing library of systematically varied imidazole compounds has been synthesized using only commercial available starting materials and straightforward reactions. Using this library of compounds, we have sought to understand and develop predictive models for thermophysical properties relating to process design, including: density, viscosity, vapor pressure, pKa and CO2 absorption capacity. Furthermore, we have discovered that imidazoles are stable in the presence of SO2 and can form reversible 1:1 adducts, which can be beneficial as SO2 is typically present at ppm levels alongside CO2 in flue gas from coal-fired power plants.
Background: Internet-based interventions can help smokers to quit compared with brief written materials or no intervention. However, they are not widely used, particularly by more disadvantaged smokers, and there is significant variation in their effectiveness. A new smoking cessation website (‘StopAdvisor’) has been systematically developed on the basis of PRIME theory, empirical evidence, web-design expertise and user-testing with socio-economically disadvantaged smokers. This paper reports the protocol of a randomised controlled trial to evaluate the efficacy of StopAdvisor and determine whether it translates across the social spectrum.
Methods: The trial has two arms with participants randomised to the offer of the interactive ‘StopAdvisor’ website (intervention condition) or a non-interactive, static website (control condition). Participants are adults from the UK, who smoke every day and are willing to make a serious quit attempt within a month of enrolment. At least 4260 participants will be recruited with a minimum of 2130 in each of two socio-economic sub-groups. The intervention comprises a structured quit plan and a variety of theory- and evidence-based behaviour change techniques for smoking cessation. Tailored support is offered in the form of a series of tunnelled sessions and a variety of interactive menus for use up to a month before, and then for one month after quitting (http://www.lifeguideonline.org/player/play/stopadvisordemonstration). The control is a static website that presents brief and standard advice on smoking cessation. Assessments are at baseline and 2-, 4- and 7-months post-enrolment. The primary outcome measure will be Russell Standard 6-months sustained abstinence, defined as self-reported continuous abstinence verified by saliva cotinine or anabasine at 7-month follow-up. Secondary outcome measures will include 7-day point-prevalence abstinence at 7-month follow-up, self-reported abstinence at 2- and 4-month follow-ups, satisfaction ratings of the website and quantitative indices of website interaction. All analyses will be by intention to treat and the main analysis will compare the two conditions on the primary outcome measure using a logistic regression model, adjusted for baseline characteristics. The efficacy of the intervention across the social spectrum will be assessed by a logistic regression focusing on the interaction between condition and socio-economic disadvantage.
High-quality data from appropriate archives are needed for the continuing improvement of radiocarbon calibration curves. We discuss here the basic assumptions behind 14C dating that necessitate calibration and the relative strengths and weaknesses of archives from which calibration data are obtained. We also highlight the procedures, problems, and uncertainties involved in determining atmospheric and surface ocean 14C/12C in these archives, including a discussion of the various methods used to derive an independent absolute timescale and uncertainty. The types of data required for the current IntCal database and calibration curve model are tabulated with examples.