Psychological outcomes of evening and night closed-loop insulin delivery under free living conditions in people with Type 1 diabetes: a 2-month randomized crossover trial.

AIM: To assess the impact on fear of hypoglycaemia and treatment satisfaction with an artificial pancreas system used for 2 consecutive months, as well as participant acceptance of the artificial pancreas system. METHODS: In a randomized crossover trial patient-related outcomes associated with an evening-and-night artificial pancreas and sensor-augmented pump therapy were compared. Both intervention periods lasted 8 weeks. The artificial pancreas acceptance questionnaire (range 0-90, higher scores better), Hypoglycaemia Fear Survey II (range 0-72, higher scores worse) and Diabetes Treatment Satisfaction Questionnaire (range 0-36, higher scores better) were completed by 32 participants. Semi-structured interviews were conducted after study completion in a subset of six participants. Outcomes were compared using a repeated-measures anova model or paired t-test when appropriate. RESULTS: The total artificial pancreas acceptance questionnaire score at the end of the artificial pancreas period was 69.1 (sd 14.7; 95% CI 63.5, 74.7), indicating a positive attitude towards the artificial pancreas. No significant differences were found among the scores at baseline, end of sensor-augmented pump therapy period or end of the artificial pancreas period with regard to fear of hypoglycaemia [28.2 (sd 17.5), 23.5 (sd 16.6) and 23.5 (sd 16.7), respectively; P = 0.099] or diabetes treatment satisfaction [29.0 (sd 3.9), 28.2 (sd 5.2) and 28.0 (sd 7.1), respectively; P = 0.43]. Themes frequently mentioned in the interviews were 'positive effects at work', 'improved blood glucose', 'fewer worries about blood glucose', but also 'frequent alarms', 'technological issues' and 'demand for an all-in-one device'. CONCLUSIONS: The psychological outcomes of artificial pancreas and sensor-augmented pump therapy were similar. Current artificial pancreas technology is promising but user concerns should be taken into account to ensure utility of these systems.

Accuracy of two continuous glucose monitoring systems: a head-to-head comparison under clinical research centre and daily life conditions.

AIMS: To assess the accuracy and reliability of the two most widely used continuous glucose monitoring (CGM) systems. METHODS: We studied the Dexcom®G4 Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6-h clinical research centre (CRC) visit. During the CRC visit, frequent venous blood glucose samples were used as reference while patients received a meal with an increased insulin bolus to induce an aggravated postprandial glucose nadir. At home, patients performed at least six reference capillary blood measurements per day. A Wilcoxon signed-rank test was performed using all data points ≥15 min apart. RESULTS: The overall mean absolute relative difference (MARD) value [standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and 16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI Δ) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Δ = 5.8-8.7%, n = 839). During the CRC visit, the MARD in the hypoglycaemic range [≤3.9 mmol/l (70 mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005, CI Δ 3.1-10.7%, n = 117). Both sensors showed higher MARD values during hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%. CONCLUSIONS: During circumstances of intended use, including both a CRC and home phase, the ENL was noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy in the hypoglycaemic range. The DG4P was less affected by this negative effect of hypoglycaemia on sensor accuracy than was the ENL.

Multicenter outpatient dinner/overnight reduction of hypoglycemia and increased time of glucose in target with a wearable artificial pancreas using modular model predictive control in adults with type 1 diabetes.

AIMS: To test in an outpatient setting the safety and efficacy of continuous subcutaneous insulin infusion (CSII) driven by a modular model predictive control (MMPC) algorithm informed by continuous glucose monitoring (CGM) measurement. METHODS: 13 patients affected by type 1 diabetes participated to a non-randomized outpatient 42-h experiment that included two evening meals and overnight periods (in short, dinner & night periods). CSII was patient-driven during dinner & night period 1 and MMPC-driven during dinner&night period 2. The study was conducted in hotels, where patients could move around freely. A CGM system (G4 Platinum; Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone-based platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA, USA) during both periods. RESULTS: A significantly lower percentage of time spent with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1: 1.96 ± 4.56% vs 12.76 ± 15.84% (mean ± standard deviation, p < 0.01), together with a greater percentage of time spent in the 3.9-10 mmol/l target range: 83.56 ± 14.02% vs 62.43 ± 29.03% (p = 0.04). In addition, restricting the analysis to the overnight phases, a lower percentage of time spent with glucose levels <3.9 mmol/l (1.92 ± 4.89% vs 12.7 ± 19.75%; p = 0.03) was combined with a greater percentage of time spent in 3.9-10 mmol/l target range in period 2 compared with period 1 (92.16 ± 8.03% vs 63.97 ± 2.73%; p = 0.01). Average glucose levels were similar during both periods. CONCLUSIONS: The results suggest that MMPC managed by a wearable system is safe and effective during evening meal and overnight. Its sustained use during this period is currently being tested in an ongoing randomized 2-month study.

Fertility awareness and parenting intentions among Mexican undergraduate and graduate university students.

An online, cross-sectional survey was carried out between November 2017 and January 2018 to assess fertility awareness among students attending the National Autonomous University of Mexico (UNAM) in Mexico City. A total of 371 students participated in the survey (n = 228 females, 143 males). 75% of females and 74% of males believed a woman's fertility begins to decline markedly after age 40. Over 75% of all participants overestimated the probability of couples having a live birth after undergoing one cycle of IVF. With regard to parenting intentions, only 48% of females wished to have children compared to 59% of males (p = 0.037) and men were more likely to have their first child at age 30 or later (71% men vs 55% women). In the event of infertility, participants had a higher preference not to have children or to pursue adoption rather than use in vitro fertilisation (IVF). In summary, university students in Mexico City demonstrated low levels of fertility awareness and a smaller proportion indicated a wish to have children than has been reported by young people elsewhere in the world.

Practical implementation of automated closed-loop insulin delivery: A French position statement.

Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.

The fixation of anti-HBsAg on plastic surfaces.

Serum samples were found to be capable of desorbing as much as 40% of the antibody to hepatitis B surface antigen (anti-HBsAg) adsorbed to plastic surfaces. This previously unreported loss could affect the accuracy of the assay, so chemical fixation was examined as a means for preventing antibody desorption during a 'sandwich' radioimmunoassay for HBsAg. Methods for fixing the anti-HBsAg were developed with glutaraldehyde and ethylchloroformate. Both methods prevented antibody desorption from polyvinylchloride and polystyrene without affecting immunoreactivity in radioimmunoassay. A combined glutaraldehyde-ethylchloroformate method resulted in stronger fixation that fully resisted the sera that caused the greatest desorption. It was found that only polymerized glutaraldehyde fixed anti-HBsAg to plastic; the monomer was ineffective. Anti-HBsAg fixed microtiter plates could be stored for at least 4 weeks without loss of sensitivity in radioimmunoassays. These methods could be adapted for use in other assays where the prevention of protein desorption from the solid phase is an important consideration.

Immunoassays at a quartz-liquid interface: theory, instrumentation and preliminary application to the fluorescent immunoassay of human immunoglobulin G.

The theoretical basis and instrumental requirements of an optical detection technique for monitoring antibody-antigen reactions at a quartz-liquid interface are described. The antibody is covalently immobilized on the optical surface of a planar, fused-quartz waveguide and reacted with antigen solution. A light beam is internally reflected within the waveguide and penetrates into the solution only a fraction of the wavelength of the incident light. This is the evanescent wave which interacts optically with the growing number of antigen-antibody complexes but minimally with the bulk solution. A two-site immunofluorescent assay for human IgG measurement is described using fluorescein as the label. The assay detection limit is approximately 0.8 micrograms/ml and individual fluorescence measurements are completed within 10 min. It is expected that this evanescent wave immunoassay should have wide applicability in both routine and research fields.

The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume.

Fifteen ovulating women had serial ultrasound scans to measure follicular, endometrial, and uterine growth, as well as biochemical indices including estradiol (E2) and the free androgen index, throughout a natural and a clomiphene-citrate-induced cycle. Despite higher E2 levels in the 5 days preceding ovulation, the clomiphene cycles were characterized by absence of the normal increase in uterine volume and an inhibition of endometrial thickening. It is proposed that the anti-estrogen effect of clomiphene inhibits the normal cyclical growth of the uterus and endometrium.

Use of artificial intelligence in analytical systems for the clinical laboratory.

OBJECTIVE: To consider the role of software in system operation, control and automation, and attempts to define intelligence. METHODS AND RESULTS: Artificial intelligence (Al) is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern-recognition and parallel processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system. In the second part of this paper, examples are given of applications of Al in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories. CONCLUSION: Al constitutes a collective form of intellectual property, and that there is a need for better documentation, evaluation and regulation of the systems already being used widely in clinical laboratories.

Dual-isotope separation technique for radioassay. Precision of calculated results affected by degree of separation.

The dual-isotope separation technique for radioassay is reviewed. An expression is derived describing the effect of counting errors on the precision of the calculated bound count rate in the dual-isotope technique. This mathematic model is tested in experiments using sodium iothalamate (I-125) as a marker in the Phadebas radiosorbent assay of cobalamin (Co-57). The coefficient of variation of results calculated on the basis of the dual-isotope technique is shown to be dependent on the amount of supernatant removed. The conclusion is that relatively large amounts of the supernatant must be removed before counting if the dual-isotope technique is to give acceptable results. The experimental model is proposed as a simple test of the suitability of a projected dual-isotope system.

Dual-isotope separation technique for radioassay of cobalamin.

Cobalamin is assayed by a dual-isotope separation method using sodium [125I]iothalamate as a marker. Two systems are used: one in which the incompletely-separated bound fraction is counted and compared with the single-isotope method in which the bound fraction is separated by washing (Phadebas radiosorbent assay); and one in which an aliquot of the free fraction is counted. In the dual-isotope method counting bound fractions, about 97% of the supernatant is removed by pouring from silicone fluid separators. The results for serum samples obtained using dual- and single-isotope methods were similar (between run coefficients of variation 5--7%). Experimental errors were smaller in the dual-isotope method. A factor in the kit standards, presumably the absence of proteins, was found to affect the separation technique, resulting in relatively large experimental errors for standards in the single-isotope method. Washing the solid phase in the single-isotope method apparently resulted in a loss of bound isotope. In the dual-isotope method counting free fractions reasonable precision was obtained (coefficient of variation of serum samples 6.6%) even though only about 56% of the supernatant (free fraction) was counted.

Dual isotope separation technique for radioassay. The effect of cross counting between two simultaneously counted isotopes.

A theoretical model, describing the effects of cross counting on the dual-isotope-corrected bound count rate and on the precision with which it is estimated, is presented. Experimental support for the validity of the model is given. The bound count rate is shown to be independent of the amount of marker isotope incorrectly counted as label isotope. The precision with which the bound count rate is estimated appears to be dependent on the size of this cross counting correction, although other factors such as pipetting errors are of more importance. Implications for the choice of assay system are discussed.

International Federation of Clinical Chemistry. Use of artificial intelligence in analytical systems for the clinical laboratory. IFCC Committee on Analytical Systems.

The incorporation of information-processing technology into analytical systems in the form of standard computing software has recently been advanced by the introduction of artificial intelligence (AI) both as expert systems and as neural networks. This paper considers the role of software in system operation, control and automation and attempts to define intelligence. AI is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern-recognition and parallel-processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system. In the second part of this paper, examples are given of applications of AI in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories. It is concluded that AI constitutes a collective form of intellectual property and that there is a need for better documentation, evaluation and regulation of the systems already being used widely in clinical laboratories.

Magnetic resonance imaging in the preoperative evaluation of cervical radiculopathy.

Forty patients with cervical radiculopathy were examined preoperatively with magnetic resonance imaging (MRI). MRI was used alone in 27 (68%) of the 40 patients; the remainder also had computed tomography in conjunction with myelography. The primary criterion on MRI for a clinically significant lesion was asymmetrical narrowing of the subarachnoid space in the region of the nerve root. Surgical confirmation of the abnormality was obtained in all 40 cases. The operative findings were a herniated nucleus pulposus (32 of 40 patients), spondylosis (2 of 40 patients), or a combination of the two (6 of 40 patients). MRI identified a surgical lesion (herniated nucleus pulposus, spondylosis, or both) in 37 of the 40 (92%) patients. We think MRI is the only preoperative imaging examination necessary in most cases of cervical radiculopathy.

Elevated free androgen index as an indicator of polycystic ovaries in oligomenorrhoea without obesity or hirsuties.

A group of oligomenorrhoeic women without obesity or hirsuties was investigated with high-resolution ultrasound, laparoscopy and biochemical parameters. In this series, polycystic ovaries (PCO), as defined by ultrasound and laparoscopy, are a common cause of oligomenorrhoea in women without the classic symptoms, and were strongly associated with an elevated free androgen index (FAI). Despite an elevated FAI, these women were not hirsute, It would seem reasonable to include a FAI in the investigation of the oligomenorrhoeic woman, along with the more 'standard' tests, such as thyroid function and a prolactin level.

Production and characterization of monoclonal antibody to gentamicin.

Splenocytes from BALB/c mice immunized with a gentamicin-hemocyanin conjugate were fused with X63-Ag8.653 murine myeloma cells to produce hybridomas that secreted monoclonal antibody to gentamicin. Sixteen positive clones were obtained. The monoclonal antibody chosen for a gentamicin immunoassay has been characterized with respect to class, subclass, type of light chain, electrophoretic homogeneity, and binding affinity. Gentamicin monoclonal antibody purified from mouse ascites fluid was analyzed by immunoelectrophoresis, double immunodiffusion, enzyme-linked immunosorbent assay (ELISA), and polyacrylamide gel electrophoresis (PAGE). The results show that the antibody is an IgG2a (kappa). Two bands were detected when the purified antibody was electrophoresed on polyacrylamide gels: a major band and a less mobile minor component (5.6% of the major band). Both were IgG2a (kappa). The major band contained antibody which bound 2.1 moles of the substrate-labeled gentamicin derivative, beta-galactosyl-umbelliferone sisomicin, per mole of IgG, whereas one mole of the minor band bound only 0.095 moles of the substrate-labeled conjugate. The antibody has an affinity constant of 1.22 X 10(10) M-1.

Lowering the cesarean rate at a small USAF hospital.

From July 1, 1988 to June 30, 1989, programs were initiated at the 93d Strategic Hospital at Castle AFB, California, to lower the cesarean (C/S) rate. Programs included vaginal birth after cesarean, external cephalic version, adequate labor documentation, and peer review of all C/S for fetal distress. One year prior (N = 467) was compared to the year after the start of these programs (N = 430). A significant decrease of 21.2% to 10.2% (p < 0.0001) was documented. We conclude that aggressive management of obstetrical patients can reduce the rate of C/S in a small USAF hospital without increasing maternal or neonatal risk.

International Federation of Clinical Chemistry. The expanding role of robotics in the clinical laboratory.

Increasing numbers of robots are going to be employed industrial chemical laboratories. Most of these will be used to reduce the monotonous tasks of sample preparation, to minimize human exposure to dangerous environments or to carry out huge numbers of repetitive experimental procedures. For example, looking for the most effective condition or combination in chemical synthesis or the best microorganism in a large number of cultures. In the clinical laboratory the situation is slightly different and robotics is not so widely applied in clinical laboratories, but there is a definite trend to employ robots or robotic systems both to reduce labor volume and exposure of employees to possible biohazards and to help get more precise and correct results. These needs will be hard to fulfill via the usual automated devices and especially when adequate devices are not available. Specially designed machines will have to be produced to satisfy these demands and robotics will play a part. Finally we need to evaluate the effectivity of introduction of robotics in terms of economy, strategy, biosafety and other aspects. Typical examples of implementation of robotics in the clinical laboratory are transportation of specimens, front-end automation of sample preparation, separation and aliquotting as well as selected processes in a large scale automation systems. As described previously, robots that are commercially available now, are not intelligent enough to be easily handled by personnel who are not trained for robotics. There is a need for personnel dedicated to robotics who join the project from the very beginning of the plan and who can maintain the system properly.(ABSTRACT TRUNCATED AT 250 WORDS)

International Federation of Clinical Chemistry (IFCC): systematic top-down approach to clinical chemistry.

This paper introduces a systematic approach to organizing the discipline of clinical chemistry. The approach is called a top-down, systems approach because it starts at the top with the most general concepts and works down through less general concepts to the most specific details and techniques. The hypothesis is that the discipline can be organized into hierarchical levels of functional processes and operational approaches to those processes. The functional processes represent what clinical scientists do; the operational approaches represent how they do it. Because functional processes change little, if at all, with time, they are use to develop a stable infrastructure or framework for the discipline. That infrastructure is then used to organize and understand operational approaches that tend to change rapidly with time in response to technological advances. This paper begins with the most general functional processes and then uses selected examples of the more general functions to illustrate lower hierarchical levels of functional processes and operational approaches.

Towards an artificial pancreas at home.

AIM: To review the recent clinical research related to the development of an artificial pancreas and the current perspectives for its home use. METHODS: All clinical investigations assessing closed-loop insulin delivery systems in diabetic patients in the literature were collected and analyzed to identify any significant advances as well as bottlenecks. RESULTS: The development of an artificial pancreas for ambulatory use offering an optimal substitute for insulin secretion has shown promising evolution over the past decade. The accumulated improvements achieved on the performance of insulin pumps using subcutaneous and intraperitoneal routes, continuous glucose monitoring and algorithms driving insulin infusion according to glucose measurement have led to numerous clinical trials recently, albeit only in a hospital setting so far. The key obstacles to achieving permanent normal glucose control are related to the delay of insulin action when infused subcutaneously or, at a lesser extent, into the peritoneal cavity, and blood glucose estimation made by subcutaneous interstitial measurement. These time lags impair the reactivity of the system, and suggest a need to develop complex algorithms aiming at their compensation. So far, manual interventions are needed at times of food intake to prevent hyper- or hypoglycaemic excursions when insulin changes rapidly. CONCLUSION: The most recent models using subcutaneous insulin infusion and glucose measurements linked by predictive control algorithms offer sufficient effectiveness and safety to consider their forthcoming use at home, during the night as a first step.