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Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service.
Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test.
Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT.
NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.
Transcatheter right ventricle decompression in neonates with pulmonary atresia and intact ventricular septum is technically challenging, with risk of cardiac perforation and death. Further, despite successful right ventricle decompression, re-intervention on the pulmonary valve is common. The association between technical factors during right ventricle decompression and the risks of complications and re-intervention are not well described.
This is a multicentre retrospective study among the participating centres of the Congenital Catheterization Research Collaborative. Between 2005 and 2015, all neonates with pulmonary atresia and intact ventricular septum and attempted transcatheter right ventricle decompression were included. Technical factors evaluated included the use and characteristics of radiofrequency energy, maximal balloon-to-pulmonary valve annulus ratio, infundibular diameter, and right ventricle systolic pressure pre- and post-valvuloplasty (BPV). The primary end point was cardiac perforation or death; the secondary end point was re-intervention.
A total of 99 neonates underwent transcatheter right ventricle decompression at a median of 3 days (IQR 2–5) of age, including 63 patients by radiofrequency and 32 by wire perforation of the pulmonary valve. There were 32 complications including 10 (10.5%) cardiac perforations, of which two resulted in death. Cardiac perforation was associated with the use of radiofrequency (p=0.047), longer radiofrequency duration (3.5 versus 2.0 seconds, p=0.02), and higher maximal radiofrequency energy (7.5 versus 5.0 J, p<0.01) but not with patient weight (p=0.09), pulmonary valve diameter (p=0.23), or infundibular diameter (p=0.57). Re-intervention was performed in 36 patients and was associated with higher post-intervention right ventricle pressure (median 60 versus 50 mmHg, p=0.041) and residual valve gradient (median 15 versus 10 mmHg, p=0.046), but not with balloon-to-pulmonary valve annulus ratio, atmospheric pressure used during BPV, or the presence of a residual balloon waist during BPV. Re-intervention was not associated with any right ventricle anatomic characteristics, including pulmonary valve diameter.
Technical factors surrounding transcatheter right ventricle decompression in pulmonary atresia and intact ventricular septum influence the risk of procedural complications but not the risk of future re-intervention. Cardiac perforation is associated with the use of radiofrequency energy, as well as radiofrequency application characteristics. Re-intervention after right ventricle decompression for pulmonary atresia and intact ventricular septum is common and relates to haemodynamic measures surrounding initial BPV.
The time required to obtain Institutional Review Board (IRB) approval is a frequent subject of efforts to reduce unnecessary delays in initiating clinical trials. This study was conducted by and for IRB directors to better understand factors affecting approval times as a first step in developing a quality improvement framework.
807 IRB-approved clinical trials from 5 University of California campuses were analyzed to identify operational and clinical trial characteristics influencing IRB approval times.
High workloads, low staff ratios, limited training, and the number and types of ancillary reviews resulted in longer approval times. Biosafety reviews and the need for billing coverage analysis were ancillary reviews that contributed to the longest delays. Federally funded and multisite clinical trials had shorter approval times. Variability in between individual committees at each institution reviewing phase 3 multisite clinical trials also contributed to delays for some protocols. Accreditation was not associated with shorter approval times.
Reducing unnecessary delays in obtaining IRB approval will require a quality improvement framework that considers operational and study characteristics as well as the larger institutional regulatory environment.
We evaluated the QX200 Droplet Digital PCR (ddPCR™, Bio-Rad) system and protocols for the detection of the tick-borne pathogens Borrelia burgdorferi and Borrelia miyamotoi in Ixodes scapularis nymphs and adults collected from North Truro, Massachusetts. Preliminary screening by nested PCR determined positive infection levels of 60% for B. burgdorferi in these ticks. To investigate the utility of ddPCR as a screening tool and to calculate the absolute number of bacterial genome copies in an infected tick, we adapted previously reported TaqMan®-based qPCR assays for ddPCR. ddPCR proved to be a reliable means for detection and absolute quantification of control bacterial DNA with precision as low as ten spirochetes in an individual sample. Application of this method revealed the average carriage level of B. burgdorferi in infected I. scapularis nymphs to be 2291 spirochetes per nymph (range: 230–5268 spirochetes) and 51 179 spirochetes on average in infected adults (range: 5647–115 797). No ticks naturally infected with B. miyamotoi were detected. The ddPCR protocols were at least as sensitive to conventional qPCR assays but required fewer overall reactions and are potentially less subject to inhibition. Moreover, the approach can provide insight on carriage levels of parasites within vectors.
We describe a versatile infrared camera/spectrograph, IRIS, designed and constructed at the Anglo-Australian Observatory for use on the Anglo-Australian Telescope. A variety of optical configurations can be selected under remote control to provide several direct image scales and a few low-resolution spectroscopic formats. Two cross-dispersed transmission echelles are of novel design, as is the use of a modified Bowen-Burch system to provide a fast f/ratio in the widest-field option. The drive electronics includes a choice of readout schemes for versatility, and continuous display when the array is not taking data, to facilitate field acquisition and focusing.
The linearity of the detector has been studied in detail. Although outwardly good, slight nonlinearities prevent removal of fixed-pattern noise from the data without application of a cubic linearising function.
Specific control and data-reduction software has been written. We describe also a scanning mode developed for spectroscopic imaging.
Our knowledge of the universe comes from recording the photon and particle fluxes incident on the Earth from space. We thus require sensitive measurement across the entire energy spectrum, using large telescopes with efficient instrumentation located on superb sites. Technological advances and engineering constraints are nearing the point where we are recording as many photons arriving at a site as is possible. Major advances in the future will come from improving the quality of the site. The ultimate site is, of course, beyond the Earth’s atmosphere, such as on the Moon, but economic limitations prevent our exploiting this avenue to the degree that the scientific community desires. Here we describe an alternative, which offers many of the advantages of space for a fraction of the cost: the Antarctic Plateau.
Surgical site infection (SSI) surveillance is performed using a variety of methods with unclear performance characteristics. We used claims data to identify records for review following hysterectomy and colorectal surgery. Claims-enhanced screening identified SSIs missed by routine surveillance and could be used for targeted chart review to improve SSI detection.
To assess the ability of Medicare claims to identify US hospitals with high rates of surgical site infection (SSI) after hip arthroplasty.
Retrospective cohort study.
Acute care US hospitals.
Fee-for-service Medicare patients 65 years of age and older who underwent hip arthroplasty in US hospitals from 2005 through 2007.
Hospital rankings were derived from claims codes suggestive of SSI, adjusted for age, sex, and comorbidities, while using generalized linear mixed models to account for hospital volume. Medical records were obtained for validation of infection on a random sample of patients from hospitals ranked in the best and worst deciles of performance. We then calculated the risk-adjusted odds of developing a chart-confirmed SSI after hip arthroplasty in hospitals ranked by claims into worst- versus best-performing deciles.
Among 524,892 eligible Medicare patients who underwent hip arthroplasty at 3,296 US hospitals, a patient who underwent surgery in a hospital ranked in the worst-performing decile based on claims-based evidence of SSI had 2.9-fold higher odds of developing a chart-confirmed SSI relative to a patient with the same age, sex, and comorbidities in a hospital ranked in the best-performing decile (95% confidence interval, 2.2-3.7).
Medicare claims successfully distinguished between hospitals with high and low SSI rates following hip arthroplasty. These claims can identify potential outlier hospitals that merit further evaluation. This strategy can also be used to validate the completeness of public reporting of SSI.
Research with laboratory species suggests that meals can be terminated by peripheral signals carried to brain feeding centres via hepatic vagal afferents, and that these signals are affected by oxidation of fuels. Pre-gastric fermentation in ruminants greatly alters fuels, allowing mechanisms conserved across species to be studied with different types and temporal absorption of fuels. These fuels include SCFA, glucose, lactate, amino acids and long-chain fatty acid (FA) isomers, all of which are absorbed and metabolised by different tissues at different rates. Propionate is produced by rumen microbes, absorbed within the timeframe of meals, and quickly cleared by the liver. Its hypophagic effects are variable, likely due to its fate; propionate is utilised for gluconeogenesis or oxidised and also stimulates oxidation of acetyl-CoA by anapleurosis. In contrast, acetate has little effect on food intake, likely because its uptake by the ruminant liver is negligible. Glucose is hypophagic in non-ruminants but not ruminants and unlike non-ruminant species, uptake of glucose by ruminant liver is negligible, consistent with the differences in hypophagic effects between them. Inhibition of FA oxidation increases food intake, whereas promotion of FA oxidation suppresses food intake. Hypophagic effects of fuel oxidation also vary with changes in metabolic state. The objective of this paper is to compare the type and utilisation of fuels and their effects on feeding across species. We believe that the hepatic oxidation theory allows insight into mechanisms controlling feeding behaviour that can be used to formulate diets to optimise energy balance in multiple species.
This Summary for Policymakers presents key findings from the Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX). The SREX approaches the topic by assessing the scientific literature on issues that range from the relationship between climate change and extreme weather and climate events (‘climate extremes’) to the implications of these events for society and sustainable development. The assessment concerns the interaction of climatic, environmental, and human factors that can lead to impacts and disasters, options for managing the risks posed by impacts and disasters, and the important role that non-climatic factors play in determining impacts. Box SPM.1 defines concepts central to the SREX.
The character and severity of impacts from climate extremes depend not only on the extremes themselves but also on exposure and vulnerability. In this report, adverse impacts are considered disasters when they produce widespread damage and cause severe alterations in the normal functioning of communities or societies. Climate extremes, exposure, and vulnerability are influenced by a wide range of factors, including anthropogenic climate change, natural climate variability, and socioeconomic development (Figure SPM.1). Disaster risk management and adaptation to climate change focus on reducing exposure and vulnerability and increasing resilience to the potential adverse impacts of climate extremes, even though risks cannot fully be eliminated (Figure SPM.2). Although mitigation of climate change is not the focus of this report, adaptation and mitigation can complement each other and together can significantly reduce the risks of climate change. [SYR AR4, 5.3]
To evaluate the use of routinely collected electronic health data in Medicare claims to identify surgical site infections (SSIs) following hip arthroplasty, knee arthroplasty, and vascular surgery.
Retrospective cohort study.
Four academic hospitals that perform prospective SSI surveillance.
We developed lists of International Classification of Diseases, Ninth Revision, and Current Procedural Terminology diagnosis and procedure codes to identify potential SSIs. We then screened for these codes in Medicare claims submitted by each hospital on patients older than 65 years of age who had undergone 1 of the study procedures during 2007. Each site reviewed medical records of patients identified by either claims codes or traditional infection control surveillance to confirm SSI using Centers for Disease Control and Prevention/ National Healthcare Safety Network criteria. We assessed the performance of both methods against all chart-confirmed SSIs identified by either method.
Claims-based surveillance detected 1.8–4.7-fold more SSIs than traditional surveillance, including detection of all previously identified cases. For hip and vascular surgery, there was a 5-fold and 1.6-fold increase in detection of deep and organ/space infections, respectively, with no increased detection of deep and organ/space infections following knee surgery. Use of claims to trigger chart review led to confirmation of SSI in 1 out of 3 charts for hip arthroplasty, 1 out of 5 charts for knee arthroplasty, and 1 out of 2 charts for vascular surgery.
Claims-based SSI surveillance markedly increased the number of SSIs detected following hip arthroplasty, knee arthroplasty, and vascular surgery. It deserves consideration as a more effective approach to target chart reviews for identifying SSIs.