Desired Target Range Research Articles

Disentangling the supply and announcement effects of open market operations

Central banks use open market operations (OMOs) to adjust the liquidity available to the financial system to maintain the short-term borrowing rate within the desired target range. Using the conditional event study methodology to decompose the impact of OMOs into supply and announcement effects, this paper finds that when OMO announcements are unexpected, the decrease in the lending rate as a result of the higher supply is significantly moderated by the announcement effect. The results highlight that central banks communicate not just through signals of their desired policy stance, but also through their announcements of operations that implement the stance.

Add-on effect of proprietary Ayurvedic medicine Diabrishta-21 in managing glucose variability measured through continuous glucose monitoring device: A case report

Abstract: In the scenario of modern health issues, Type 2 Diabetes Mellitus (T2DM) has gained much importance as “adult-onset diabetes” which represents a combination of genetic, environmental, and lifestyle choices. It predominantly shows hyperglycemia or increased blood glucose levels, insulin deficiency, and insulin resistance, which typically characterizes this metabolic disorder whilst manifesting life-threatening complications. This report presents the case of a 55-year-old male with T2DM whose glucose levels were monitored during a period when he was on his prescribed antidiabetic medicines, followed by the addition of an Ayurvedic preparation Diabrishta-21. His glucose summary, obtained by the Continuous Glucose Monitoring (CGM) approach depicts a change in the average value of blood sugar levels and glycated hemoglobin levels, decreasing from 167 to 108 mg/dL, and from 7.4% to 5.4%, respectively. Moreover, the percentage of time the blood glucose levels were in the desired target range increased from 29% to 79%. Thus, Diabrishta-21 in this case report appears to be beneficial in the management of T2DM by aiding in controlling the glucose variability and lowering the blood glucose levels.

Artificial pancreas control using optimized fuzzy logic based genetic algorithm

The aim of this paper is to develop an artificial pancreas that can automate the process of monitoring blood glucose levels and administering insulin to diabetic patients. The device incorporates a fuzzy controller that is optimized through a genetic algorithm and designed using MATLAB. The system comprises three key components: a continuous glucose monitoring (CGM) system, an insulin pump, and the fuzzy controller. The CGM measures blood glucose levels in real-time, and the insulin pump administers insulin doses to maintain blood glucose levels within a specific range. The fuzzy controller adjusts the insulin delivery rate based on the patient's blood glucose levels and their target range. To enhance the system's performance, a genetic algorithm is used to fine-tune the parameters of the fuzzy controller, seeking the optimal set of parameters that minimize the difference between the patient's blood glucose levels and the desired target range. The system is implemented in MATLAB, and simulation results indicate its effectiveness in maintaining blood glucose levels within the desired target range, reducing the risk of hypoglycemia and hyperglycemia. In summary, the proposed artificial pancreas system provides an effective automated solution for monitoring blood glucose levels and administering insulin to diabetic patients, with the fuzzy controller and genetic algorithm optimization enhancing the system's performance.

#5859 A NEW ULTRAFILTRATION RATE FEEDBACK CONTROLLER FOR ATTAINMENT OF RELATIVE BLOOD VOLUME TARGETS DURING HEMODIALYSIS

Abstract Background and Aims Preciado et al. (NDT, 2019) have identified half-hourly relative blood volume (RBV) targets during hemodialysis (HD) that are associated with significantly improved patient survival. Attainment of these RBV targets would necessitate incessant adjustments to the ultrafiltration rate (UFR) by the dialysis nurse, which is logistically not feasible. We developed a proportional-integral controller (Casper et al., Int J Artif Organs, 2022) that takes RBV data from the commercially available CLiC® device as an input and provides UFR suggestions to guide the RBV curve into the desired targets. The clinician pre-specifies the desired UF goal and the maximum allowed upward/downward deviation from this goal. The Controller then optimizes the RBV trajectory within the limits allowed by the clinician's prescription. The present study aimed to characterize the performance of this feedback controller. Methods We conducted a single-arm, prospective, interventional pilot study in subjects on chronic HD at three Avantus Renal Therapy dialysis centers in New York City. Subjects were treated with Fresenius 2008T HD machines. RBV was measured with the CLiC® device. CLiC® and HD machine data were fed into a research laptop running the UFR Feedback Controller software. The UFR recommendations (generated every 10 minutes) were evaluated by dialysis nurses, who then either implemented or disregarded them as they deemed clinically appropriate. The nurses were instructed to only override Controller recommendations if medically indicated, but not in an attempt to manage the subjects’ RBV trajectories themselves. RBV target range attainment with the UFR Feedback Controller was compared to standard of care treatments (data obtained retrospectively) in the same subjects. Results Fifteen subjects (58.9 ± 15.3 years, dialysis vintage 4.1 ± 2.4 years, baseline interdialytic weight gain 2.6 ± 0.8 L, treatment time 222 ± 28 min) were studied prospectively with the UFR Feedback Controller (63 study visits, 4.2 ± 1.9 visits per subject). Nine subjects contributed at least two complete treatments to each study period (Controller and standard of care, respectively) and were included in this analysis. The probabilities of achieving an RBV within the desired target range for each timepoint, stratified by study period (standard of care versus UFR Feedback Controller), are shown in the Figure. Use of the Controller was associated with a higher rate of RBV target range attainment for every timepoint. We confirmed these results with generalized linear mixed-effects models: Across all RBV target timepoints, use of the Controller was a significant predictor of better RBV target range attainment (P < 0.0001). Use of the UFR Feedback Controller was a significant predictor of RBV target range attainment for timepoints 60, 90, 120, and 150 minutes, and a borderline significant predictor for timepoints 30 and 180 minutes. Conclusion Use of this UFR Feedback Controller was associated with a significant and clinically meaningful increase in RBV target range attainment. This technology individualizes the UFR to the patient's plasma refill kinetics during the HD treatment and may assist clinicians with optimizing fluid management in their patients.

Artificial intelligence-augmented histopathologic review using image analysis to optimize DNA yield from formalin-fixed paraffin-embedded slides

To achieve minimum DNA input requirements for next-generation sequencing (NGS), pathologists visually estimate macrodissection and slide count decisions. Unfortunately, misestimation may cause tissue waste and increased laboratory costs. We developed an artificial intelligence (AI)-augmented smart pathology review system (SmartPath) to empower pathologists with quantitative metrics for accurately determining tissue extraction parameters. SmartPath uses two deep learning architectures, a U-Net based network for cell segmentation and a multi-field-of-view convolutional network for tumor area segmentation, to extract features from digitized H&E-stained formalin-fixed paraffin-embedded slides. From the segmented tumor area, SmartPath suggests a macrodissection area. To predict DNA yield per slide, the extracted features from within the macrodissection area are correlated with known DNA yields to fit a regularized linear model (R = 0.85). Then, a pathologist-defined target yield divided by the predicted DNA yield per slide gives the number of slides to scrape. Following model development, an internal validation trial was conducted within the Tempus Labs molecular sequencing laboratory. We evaluated our system on 501 clinical colorectal cancer slides, where half received SmartPath-augmented review and half traditional pathologist review. The SmartPath cohort had 25% more DNA yields within a desired target range of 100–2000 ng. The number of extraction attempts was statistically unchanged between cohorts. The SmartPath system recommended fewer slides to scrape for large tissue sections, saving tissue in these cases. Conversely, SmartPath recommended more slides to scrape for samples with scant tissue sections, especially those with degraded DNA, helping prevent costly re-extraction due to insufficient extraction yield. A statistical analysis was performed to measure the impact of covariates on the results, offering insights on how to improve future applications of SmartPath. With these improvements, AI-augmented histopathologic review has the potential to decrease tissue waste, sequencing time, and laboratory costs by optimizing DNA yields, especially for samples with scant tissue and/or degraded DNA.

Patients With Infantile Nephropathic Cystinosis in Germany and Austria: A Retrospective Cohort Study.

BackgroundInfantile nephropathic cystinosis (INC) is a rare lysosomal storage disorder resulting in progressive chronic kidney disease (CKD) and a variety of extrarenal manifestations. This orphan disease remains a challenge for patients, their families and health care providers. There is currently no comprehensive study on patients' clinical course in Germany and Austria.MethodsA retrospective cohort study including 74 patients at eleven centers of care was conducted. Data on time of diagnosis, CKD stage, leukocyte cystine levels (LCL), extrarenal manifestations, and treatment was collected from medical charts and subsequently analyzed using explorative statistics. Age at initiation of kidney replacement therapy (KRT) was evaluated by Kaplan–Meier analyses for different groups of patients.ResultsPatients were diagnosed at a median age of 15 months (IQR: 10–29, range: 0–110), more recent year of birth was not associated with earlier diagnosis. Oral cystine-depleting therapy (i.e., cysteamine) was prescribed at a median dose of 1.26 g/m2 per day (IQR: 1.03–1.48, range: 0.22–1.99). 69.2% of all 198 LCL measurements of 67 patients were within the desired target range (≤ 1 nmol cystine/mg protein). Median time-averaged LCLs per patient (n = 65) amounted to 0.57 nmol cystine/mg protein (IQR: 0.33–0.98, range: 0.07–3.13) when considering only values at least 1 year after initiation of therapy. The overall median height of 242 measurements of 68 patients was at the 7th percentile (IQR: 1–25, range: 1–99). 40.5% of the values were ≤ the 3rd percentile. Patient sex and year of birth were not associated with age at initiation of KRT, but patients diagnosed before the age of 18 months required KRT significantly later than those patients diagnosed at the age of ≥ 18 months (p = 0.033): median renal survival was 21 years (95% CI: 16, -) vs. 13 years (95% CI, 10, -), respectively.ConclusionEarly diagnosis and initiation of cystine depleting therapy is important for renal survival in children with INC. Cysteamine doses and LCL showed that treatment in this cohort met international standards although there is great interindividual variety. Patient growth and other aspects of the disease should be managed more effectively in the future.

Efficacy and safety of a new insulin infusion protocol adapted for the target glycemic range of 140–180 mg/dl in adult critical care units: a tertiary care centre experience

In critical care setting, insulin infusion rather than subcutaneous insulin is recommended to maintain the blood glucose (BG) level in the target range. We have devised an insulin infusion protocol which requires monitoring of blood glucose and insulin dose adjustment one hourly. In this study, we have studied the efficacy of our insulin infusion protocol (IIP) in terms of bringing and maintaining blood glucose to target range, and its safety in terms of preventing hypoglycemia. It is a retrospective review of all patients who received insulin infusion from the 1st of July 2017 to the 30th of June 2018. A total of 231 were included and data pertaining to demographic details and related to insulin infusion was documented in a predefined questionnaire. Insulin infusion was continued for a mean duration of 26.3 ± 13.7 h taking 5.7 ± 3.1 h to reach the target BG level 180 mg/dl) but the mean BG remains 168.95 ± 45.52 within the desired target range. Our insulin infusion protocol not only achieved and maintained the blood glucose in the target range, it is safe with a very low risk of hypoglycemia.

Adjusting mean arterial pressure alarms improves the time spent within blood pressure targets in patients with septic shock: A quasi-experimental study

BackgroundNorepinephrine is the first-line vasoactive drug in septic shock. As underdosages or overdosages can be harmful for patients, it seems useful to maintain the mean arterial pressure (MAP) within preset bounds. ObjectivesWe sought to assess whether adjusted MAP alarms could improve MAP control in patients with septic shock. MethodsWe conducted a quasi-experimental before-and-after study. During two consecutive periods, data on MAP control were obtained from patients with septic shock (n = 50/period) treated with norepinephrine over more than 24 h. The norepinephrine administration protocol, including prescription of the MAP target range (e.g., 65–75 mmHg), was identical during the two periods. During the first period (control group), the preset alarms of the monitor were used (i.e., low and high systolic blood pressure alarms set at 90 and 160 mmHg, respectively). During the second period, adjusted MAP alarms were implemented, with upper and lower bounds corresponding to the prescribed MAP target range (MAP-Alarm group). The primary end point was the percentage of time outside the desired MAP target range during the first 24 h of norepinephrine infusion. ResultsBaseline characteristics were not significantly different. The primary end point was significantly lower in the MAP-Alarm group than in the control group (25 ± 13% versus 51 ± 18%, respectively; p < 0.01). MAP was higher than the target 14 ± 11% of the time in the MAP-Alarm group versus 37 ± 17% in the control group (p < 0.01) and lower than the target 11 ± 9% of the time in the MAP-Alarm versus 21 ± 22% in the control group (p < 0.05). There was no significant difference between the two groups with regard to the dose of norepinephrine, duration of norepinephrine administration, and survival. ConclusionsThese results suggest that adjusting MAP alarms to the desired MAP target range could dramatically improve the percentage of time spent within MAP targets in patients with septic shock but does not reduce exposure to norepinephrine.

P1079NOVEL ULTRAFILTRATION RATE FEEDBACK CONTROLLER FOR ATTAINMENT OF RELATIVE BLOOD VOLUME TARGETS DURING HEMODIALYSIS

Abstract Background and Aims Preciado et al. have identified half-hourly relative blood volume (RBV) targets (at 30, 60…180 min) during hemodialysis (HD) that are associated with significantly improved patient survival. Attainment of these RBV targets would necessitate incessant adjustments to the ultrafiltration rate (UFR) by the dialysis nurse, which is logistically not feasible. We developed a novel proportional-integral controller that takes RBV data from the commercially available CLiC® device as an input and provides UFR suggestions to guide the RBV curve into the desired targets. The clinician specifies the desired UF goal and the maximum allowed upward/downward deviation from this goal, and the Controller then optimizes the RBV trajectory within the limits allowed by the clinician’s prescription. The present study is aimed to characterize the behavior of this novel feedback controller. Method We conducted a single-arm, prospective, interventional pilot study in subjects on chronic HD at three Avantus Renal Therapy Dialysis Centers in New York City. Subjects were treated with Fresenius 2008T HD machines. RBV was measured with the CLiC® device. CLiC® and HD machine data were fed into a research laptop running the UFR Feedback Controller software. The UFR recommendations (generated every 10 minutes) were evaluated by dialysis nurses who then either implemented or rejected them as they deemed clinically appropriate. The nurses were instructed to only override Controller recommendations if medically indicated, but not in an attempt to manage the subjects’ RBV trajectories themselves. Results Fifteen subjects (58.9 ± 15.3 years, 33% white, 53% black, dialysis vintage 4.1 ± 2.4 years, baseline interdialytic weight gain 2.6 ± 0.8 L, treatment time 222 ± 28 min) were studied (63 study visits, 4.2 ± 1.9 visits per subject). Of 300 analyzed RBV target timepoints, 63% had RBVs within the desired target range, 33% of the RBVs were above and 4% were below target. Stratified by timepoint, the on-target percentage increased from 37% at 30 min to 73% at 180 min into HD, while the proportion of RBVs above or below target decreased. In subjects with at least 4 complete study visits (N=8), looking at each of their first 4 complete visits, on average 71.8% of subjects were within the desired RBV target at 180 min into HD. The rate of intradialytic morbid events did not appear to be outside of the ordinary. There was no indication of adverse events related to the use of the UFR Feedback Controller. The Figure shows an example study visit where the UFR Feedback Controller modulates the UFR on an ongoing basis throughout the treatment to keep the RBV curve close to the ideal target trajectory (red line, defined by connecting the RBVs associated with the lowest all-cause mortality). Solid black line: RBV curve (left y-axis); dashed black line: UFR (right y-axis); green boxes: half-hourly RBV target ranges associated with improved survival. Conclusion The UFR Feedback Controller behaves as expected, steering the patients’ RBV curves toward the predefined target ranges where possible, while simultaneously guaranteeing that the prescribed fluid removal goal will be achieved. Preciado et al. had reported approx. one third of patients within the favorable RBV target range at 3h into HD. In contrast, while our pilot study was relatively small, with use of our novel UFR Feedback Controller, approx. 72% of subjects were within the desired RBV target range at 3h into HD. This novel UFR feedback control technology holds great promise for improving fluid management and clinical outcomes in HD patients without requiring additional staff time.

Positioning time in range in diabetes management.

Recent upswings in the use of continuous glucose monitoring (CGM) technologies have given people with diabetes and healthcare professionals unprecedented access to a range of new indicators of glucose control. Some of these metrics are useful research tools and others have been welcomed by patient groups for providing insights into the quality of glucose control not captured by conventional laboratory testing. Among the latter, time in range (TIR) is an intuitive metric that denotes the proportion of time that a person's glucose level is within a desired target range (usually 3.9-10.0mmol/l [3.5-7.8mmol/l in pregnancy]). For individuals choosing to use CGM technology, TIR is now often part of the expected conversation between patient and healthcare professional, and consensus recommendations have recently been produced to facilitate the adoption of standardised TIR targets. At a regulatory level, emerging evidence linking TIR to risk of complications may see TIR being more widely accepted as a valid endpoint in future clinical trials. However, given the skewed distribution of possible glucose values outside of the target range, TIR (on its own) is a poor indicator of the frequency or severity of hypoglycaemia. Here, the state-of-the-art linking TIR with complications risk in diabetes and the inverse association between TIR and HbA1c are reviewed. Moreover, the importance of including the amount and severity of time below range (TBR) in any discussions around TIR and, by inference, time above range (TAR) is discussed. This review also summarises recent guidance in setting 'time in ranges' goals for individuals with diabetes who wish to make use of these metrics. For most people with type 1 or type 2 diabetes, a TIR >70%, a TBR <3.9mmol/l of <4%, and a TBR <3.0mmol/l of <1% are recommended targets, with less stringent targets for older or high-risk individuals and for those under 25years of age. As always though, glycaemic targets should be individualised and rarely is that more applicable than in the personal use of CGM and the data it provides.

Efficacy of Needling Revision After XEN Gel Stent Implantation: A Prospective Study

The XEN gel stent is currently the only minimally invasive glaucoma surgical device that targets the subconjunctival outflow pathway through an ab interno placement. It has demonstrated a significant intraocular pressure (IOP)-lowering potential and a favorable safety profile compared with traditional filtering surgery. However, despite a less invasive approach, the presence of a filtering bleb inevitably implies some risk of complications. The most commonly reported bleb-related complication, with rates as high as 45%, is bleb fibrosis associated with raised IOP. To restore filtration in those failing blebs, needling revision is considered the procedure of choice. In this study, we present the results of mitomycin C-augmented needling after XEN implantation. This was a prospective, interventional study, conducted at a single tertiary glaucoma center. Fifty-one eyes of 51 patients with raised IOP associated with either a fibrotic or shallow bleb or increased vascularity following XEN gel stent implantation at the investigation site between January 2015 and June 2016 were enrolled in this study. Patients with other identified causes of filtration failure (stent malposition, internal ostium obstruction, retained viscoelastic) were excluded. Included patients who underwent mitomycin C-augmented needling revision, and follow-up examinations were conducted at 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months. The primary outcome was the magnitude of IOP reduction following needling revision at the last follow-up visit. Secondary outcome measures were the number of needling procedures carried out in all patients, the rate of patients requiring further filtering surgery following needling revision, and the rate of intraoperative and postoperative complications associated with needling revisions. The average age was 74.4±9.6 years; 66.7% (n=34) were female individuals. Primary open-angle glaucoma was the most common diagnosis (n=21, 41.2%). A total of 78 needling procedures were performed over the 24-month follow-up. Overall 20 of 51 eyes (39.2%) required >1 needling revision, and 14 eyes (24.5%) eventually required reoperation to maintain IOP within their desired target range. Before XEN implantation, mean preoperative IOP was 22.3±8.2 mm Hg and decreased to 14.1±8.0 mm Hg at day 1 postoperatively (-36.8%). The last measured IOP before the first needling revision was on average 23.6±8.9 mm Hg, which reduced to a mean 12.1±4.2 mm Hg at the first postrevision appointment (-48.7%). At the last follow-up appointment, on average 17.0±7.0 months after the first needling, the mean IOP was 14.3±4.1 mm Hg (-35.9% and -39.4% from preoperative and prerevision baselines, respectively). Complications associated with needling revisions were partial amputation of the XEN implant during needling (n=2, 3.9%), hypotony with choroidal detachment (n=1, 2%), and failure to achieve target IOP requiring subsequent surgery (n=14, 27.5%). No association was found between any of the recorded characteristics and the number of needling revisions performed or their outcomes. The present study shows that needling revision following XEN gel stent implantation is a relatively safe and efficient intervention to restore filtration in failing blebs, with a significant and durable IOP-reduction potential.

Evaluation of an updated sedation protocol to reduce benzodiazepines in a pediatric intensive care unit

Aim: Midazolam like other benzodiazepines is supposed to be neurotoxic in small children and to represent a risk factor for the development of delirium. The aim of this study was to evaluate whether a modified analgesia and sedation protocol is feasible and effective to reduce the requirement of midazolam in neonates and young infants after cardiac surgery.Methods: Patients aged 6 months or younger who underwent surgery for congenital heart disease with cardiopulmonary bypass were enrolled and divided into a pre-modification group (January–December 2016) and after adjusting our sedation protocol into a post-modification group (January–December 2018). We assessed the doses of midazolam, morphine and clonidine as well as sedation scores according to our nurse-driven sedation protocol every 8 h until 120 h after cardiac surgery. During weaning from analgesia and sedation, children were monitored regarding withdrawal symptoms and pediatric delirium.Results: Sixty-five patients were included (33 patients in the pre-modification group, 32 patients in the post-modification group). The number of patients receiving midazolam and the cumulative dose of midazolam could be successfully reduced. The sedation scores were still within the desired target range for adequate sedation without any negative side effects.Conclusions: It is feasible and safe to reduce the use of midazolam in infants after cardiac surgery maintaining sedation goals based on a modified nurse-driven analgesia and sedation protocol.

Personalized ESA doses for anemia management in hemodialysis patients with end‐stage renal disease

AbstractEnd‐stage renal disease (ESRD) patients receiving hemodialysis are typically anemic due to a lack of erythropoietin (EPO), a hormone required for red blood cell (RBC) production. EPO replacement therapy is complex, often resulting in oscillating hemoglobin (Hb) levels. EPO dosing protocols do not account for endogenous delays and appear to contribute to, if not cause, Hb variability. The Mayo Clinic Anemia Management System (MCAMS) is based on a physiological simulation of the production and lifespan of RBCs, driven by EPO dosage schedules. Patient‐specific parameters were found such that simulated Hb levels matched historical Hb levels in response to historical EPO doses. The calibrated model was used to identify new dosing regimens that stabilize Hb. MCAMS has been used to recommend individualized EPO dosage regimens to maintain stable Hb levels within a desired target range for more than 600 patients, improving patient outcomes while reducing medication costs by about 40 percent.© 2018 System Dynamics Society

Clinical Performance and Safety of Closed-Loop Systems: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Automated systems can improve the stability of controlled variables and reduce the workload in clinical practice without increasing the risks to patients. We conducted this review and meta-analysis to assess the clinical performance of closed-loop systems compared with manual control. Our primary outcome was the accuracy of closed-loop systems in comparison with manual control to maintain a given variable in a desired target range. The occurrence of overshoot and undershoot episodes was the secondary outcome. We retrieved randomized controlled trials on accuracy and safety of closed-loop systems versus manual control. Our primary outcome was the percentage of time during which the system was able to maintain a given variable (eg, bispectral index or oxygen saturation) in a desired range or the proportion of the target measurements that was within the required range. Our secondary outcome was the percentage of time or the number of episodes that the controlled variable was above or below the target range. The standardized mean difference and 95% confidence interval (CI) were calculated for continuous outcomes, whereas the odds ratio and 95% CI were estimated for dichotomous outcomes. Thirty-six trials were included. Compared with manual control, automated systems allowed better maintenance of the controlled variable in the anesthesia drug delivery setting (95% CI, 11.7%-23.1%; percentage of time, P < 0.0001, number of studies: n = 15), in patients with diabetes mellitus (95% CI, 11.5%-30.9%; percentage of time, P = 0.001, n = 8), and in patients mechanically ventilated (95% CI, 1.5%-23.1%; percentage of time, P = 0.03, n = 8). Heterogeneity among the studies was high (>75%). We observed a significant reduction of episodes of overshooting and undershooting when closed-loop systems were used. The use of automated systems can result in better control of a given target within a selected range. There was a decrease of overshooting or undershooting of a given target with closed-loop systems.

Sub-Nyquist sampling and detection in Costas coded pulse compression radars

Modern pulse compression radar involves digital signal processing of high bandwidth pulses modulated with different coding schemes. One of the limiting factors in the radar’s design to achieve desired target range and resolution is the need of high rate analog-to-digital (A/D) conversion fulfilling the Nyquist sampling criteria. The high sampling rates necessitate huge storage capacity, more power consumption, and extra processing requirement. We introduce a new approach to sample wideband radar waveform modulated with Costas sequence at a sub-Nyquist rate based upon the concept of compressive sensing (CS). Sub-Nyquist measurements of Costas sequence waveform are performed in an analog-to-information (A/I) converter based upon random demodulation replacing traditional A/D converter. The novel work presents an 8-order Costas coded waveform with sub-Nyquist sampling and its reconstruction. The reconstructed waveform is compared with the conventionally sampled signal and depicts high-quality signal recovery from sub-Nyquist sampled signal. Furthermore, performance of CS-based detections after reconstruction are evaluated in terms of receiver operating characteristic (ROC) curves and compared with conventional Nyquist-rate matched filtering scheme.

Household financial burden of phenylketonuria and its impact on treatment in China: a cross-sectional study

SummaryBackgroundPhenylketonuria (PKU) is a rare inborn disease, which, untreated, leading to severe neurobehavioral dysfunction. Considering its complexity, the management of PKU may bring a formidable economic burden to parents and caregivers. It is still unknown what the out-of-pocket expenses are for a patient with PKU in China. This paper explores the household financial burden of classical PKU and its impact on Chinese families in a quantitative manner for the first time.MethodsA non-interventional and observational study was conducted at the China-Japan Friendship Hospital, one of the national centers for inherited metabolic disorders in China. The medical and non-medical household financial burdens were consolidated into a questionnaire to evaluate the out-of-pocket costs (OOPCs) of PKU treatment and follow-up.FindingsThe total OOPCs were USD$3766.1 (0y), USD$3795.2 (1–2 ys), USD$4657.7 (3–4 ys), USD$5979.9 (5–8 ys), and USD$5588.7 (9 ys and older) for PKU patients of different age groups. The median economic burden of classical PKU was 75.0 % of total annual family income (range 1.0–779.1 %), and 94.4 % of the families exceeding the threshold considered as catastrophic expenditure. There was a negative correlation between the financial burden and the proportion of time when Phe concentrations were in the desired target range (120–250 μmol/L) in 0–4-ys group (r = -0.474, p = 0.026).ConclusionsThe management of PKU is associated with a severe financial burden on patients’ families, which may lead to insufficient treatment or variation of blood Phe concentration. The current reimbursement policies are as yet inadequate. A national reimbursement system targeting treatment practices for PKU patients and other rare diseases across China is imperative.

Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5(*)3 genotype in Chinese renal transplant recipients.

To examine how the endogenous CYP3A4 phenotype and CYP3A5(*)3 genotype of Chinese renal transplant recipients influenced the dose-corrected trough concentration (C0/D) and weight-corrected daily dose (D/W) of tacrolimus. A total of 101 medically stable kidney transplant recipients were enrolled, and their blood and urine samples were gathered. The endogenous CYP3A4 phenotype was assessed by the ratio of 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone in urine. CYP3A5(*)3 genotype was determined using PCR-RELP. In overall renal transplant recipients, a multiple regression analysis including the endogenous CYP3A4 phenotype, CYP3A5(*)3 genotype and post-operative period accounted for 60.1% of the variability in C0/D ratio; a regression equation consisting of the endogenous CYP3A4 phenotype, post-operative period, body mass index, CYP3A5(*)3 genotype, gender, total bilirubin and age explained 61.0% of the variability in D/W ratio. In CYP3A5(*)3/(*)3 subjects, a combination of the endogenous CYP3A4 phenotype, post-operative period and age was responsible for 65.3% of the variability in C0/D ratio; a predictive equation including the endogenous CYP3A4 phenotype, post-operative period, body mass index, gender and age explained 61.2% of the variability in the D/W ratio. Base on desired target range of tacrolimus trough concentrations, individual daily dosage regimen was calculated, and all the observed daily doses were within the predicted range. This study provides the equations to predict tacrolimus metabolism and dosage requirements based on the endogenous CYP3A4 phenotype, CYP3A5(*)3 genotype and other non-genetic variables.

Oxygen targeting in preterm infants: a physiological interpretation.

Randomized controlled trials evaluating low-target oxygen saturation (SpO2:85% to 89%) vs high-target SpO2 (91% to 95%) have shown variable results regarding mortality and morbidity in extremely preterm infants. Because of the variation inherent to the accuracy of pulse oximeters, the unspecified location of probe placement, the intrinsic relationship between SpO2 and arterial oxygen saturation (SaO2) and between SaO2 and partial pressure of oxygen (PaO2) (differences in oxygen dissociation curves for fetal and adult hemoglobin), the two comparison groups could have been more similar than dissimilar. The SpO2 values were in the target range for a shorter period of time than intended due to practical and methodological constraints. So the studies did not truly compare 'target SpO2 ranges'. In spite of this overlap, some of the studies did find significant differences in mortality prior to discharge, necrotizing enterocolitis and severe retinopathy of prematurity. These differences could potentially be secondary to time spent beyond the target range (SpO2 <85 or >95%) and could be avoided with an intermediate but wider target SpO2 range (87% to 93%). In conclusion, significant uncertainty persists about the desired target range of SpO2 in extremely preterm infants. Further studies should focus on studying newer methods of assessing oxygenation and strategies to limit hypoxemia (<85% SpO2) and hyperoxemia (>95% SpO2).

Unterschiedliche Effekte der Trabektomoperation auf unterschiedliche Glaukomformen

Ab interno trabeculotomy using the trabectome device is a intraocular pressure (IOP) decreasing operation by ablation of the trabecular meshwork and the inner wall of Schlemm's channel. This prospective study analyses the effectiveness of the trabectome operation in 122 patients. The operation was conducted when topical medication was maxed out with the intraocular pressure (IOP) remaining above the desired target range. In addition to the evaluation of the whole study group further analysis concerned the effectiveness of the trabectome in different subclassifications of glaucoma. In some cases the procedure was combined with cataract surgery and subsequently the results were compared to the plain trabectome OP. The results were split into two groups: "complete success" (without postoperative medication) and "qualified success" (with medication). The evaluation was processed for the IOP levels ≤ 21 mmHg, ≤ 18 mmHg, ≤ 15 mmHg und ≤ 12 mmHg. Follow-up dates were 6 and 12 months after surgery. Baseline IOP was 20.15 ± 7.1 mmHg. After 6 months the average IOP of all patients was 16.53 ± 5.89 mmHg, after 12 months the IOP amounted to 15.6 ± 4.45 mmHg. At both follow-ups approximately 90 % of the "complete success" group exhibited an IOP ≤ 18 mmHg. Also at both follow-ups 75 % of the "qualified success" group achieved a range ≤ 18 mmHg - whereas 50 % gained an IOP ≤ 15 mmHg. In secondary glaucoma an IOP decrease of 36 % was achieved. In open-angle glaucomas and those with dysgenetic altered angles the operation evoked a pressure loss of ca. 20 %. The trabectome-only group as well as the group of combined surgery exhibited a significant lowering of IOP. This was accomplished by a significant reduction of eye drops. After surgery nearly half of all patients required none or 1 eye drop at most. The trabectome offers a safe and significant lowering of IOP for around 36 % and seems to be very effective in secondary glaucomas. In dysgenetic alterations and open-angle glaucoma a moderate lowering of IOP (ca. 20 %) may be expected. The amount of eye drops can be reduced for about 42 %. After surgery every second patient requires at most 1 eye drop. The technique can be combined with cataract surgery and permits a penetrating operation at a later date.

P06 Automated control of inspired oxygen in ventilated newborn infants: a randomised crossover study

BackgroundThe risks associated with hyperoxia as well as hypoxia, particularly in the preterm newborn, are well described. Although it is the standard of care for ventilated infants requiring supplemental oxygen...