Accuracy of Bilistick (a Point-of-Care Device) to Detect Neonatal Hyperbilirubinemia.

INTRODUCTION: Early diagnosis and appropriate management of neonatal jaundice is crucial in avoiding severe hyperbilirubinemia and brain injury. A low-cost, minimally invasive, point-of-care (PoC) tool for total bilirubin (TB) estimation which can be useful across all ranges of bilirubin values and all settings is the need of the hour. OBJECTIVE: To assess the accuracy of Bilistick system, a PoC device, for measurement of TB in comparison with estimation by spectrophotometry. DESIGN/METHODS: In this cross-sectional clinical study, in infants who required TB estimation, blood samples in 25-µl sample transfer pipettes were collected at the same time from venous blood obtained for laboratory bilirubin estimation. The accuracy of Bilistick in estimating TB within ±2 mg/dl of bilirubin estimation by spectrophotometry was the primary outcome. RESULTS: Among the enrolled infants, 198 infants were eligible for study analysis with the mean gestation of 36 ± 2.3 weeks and the mean birth weight of 2368 ± 623 g. The median age at enrollment was 68.5 h (interquartile range: 48-92). Bilistick was accurate only in 54.5% infants in measuring TB within ±2 mg/dl difference of TB measured by spectrophotometry. There was a moderate degree of correlation between the two methods (r = 0.457; 95% CI: 0.339-0.561, p value < 0.001). Bland-Altman analysis showed a mean difference of 0.5 mg/dl (SD ± 4.4) with limits of agreement between -8.2 and +9.1 mg/dl. CONCLUSION: Bilistick as a PoC device is not accurate to estimate TB within the clinically acceptable difference (±2 mg/dl) of TB estimation by spectrophotometry and needs further improvement to make it more accurate.

The impact of free medical supplies and regular telephonic contact on glycemic control in Indian children and adolescents with type 1 diabetes.

BACKGROUND/OBJECTIVE: The effect of economic assistance to underprivileged families with type 1 diabetes has never been described. Such a study is relevant as logistic and cultural factors may preclude an anticipated good outcome. The objective of the study is to determine the impact of economic and educational intervention on hemoglobin A1c (HbA1c) and diabetes knowledge. METHODS: Eighty-five consecutive participants were prospectively provided insulin and glucose strips for 1 year. From the 6th to 12th month, patients were randomized such that half of them (telephone group) received proactive telephonic advice by a diabetes educator, while the non-telephone group received usual care. HbA1c and diabetes knowledge were measured at baseline, 6 and 12 months. RESULTS: Significant improvement was seen in HbA1c with provision of free diabetes supplies, when patients were compared with their own HbA1c values during the prior 36 months (baseline [8.38 ± 2.0%], at 3 months [8.0 ± 1.6%] and at 6 months [8.1 ± 1.5%, P = 0.0106]). Knowledge score increased from baseline (48 ± 15) to 6 months (58 ± 13, P < 0.001). No difference was seen between the telephone and non-telephone groups in HbA1c from the 6th to 9th and 12th month. The knowledge score showed significant improvement in the telephone group during the proactive telephonic advice study compared with the non-telephone group (P = 0.002). CONCLUSIONS: The provision of free medical supplies improved HbA1c and diabetes knowledge. Intensive telephone contact improved knowledge, not HbA1c. These results provide important background for policy makers and diabetes management teams.

Synergistic Tailoring of Electrostatic and Hydrophobic Interactions for Rapid and Specific Recognition of Lysophosphatidic Acid, an Early-Stage Ovarian Cancer Biomarker.

Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetylenes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through the synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone with a concomitant blue-to-red color change. The detailed mechanism underlying the high selectivity of PDAs toward LPA is revealed by comprehensive theoretical calculation and experiments. Moreover, the level of LPA can be quantified in plasma samples from both mouse xenograft tumor models and patients with ovarian cancer. Impressively, this approach can be introduced into a portable point-of-care device to successfully distinguish the blood samples of patients with ovarian cancer from those of healthy people, with 100% accuracy. This work provides a valuable portable tool for early diagnosis of ovarian cancer and thus holds a great promise to dramatically improve the overall survival.

The Diagnosis of Urinary Tract Infection in Young Children (DUTY) Study Clinical Rule: Economic Evaluation.

OBJECTIVE: To estimate the cost-effectiveness of a two-step clinical rule using symptoms, signs and dipstick testing to guide the diagnosis and antibiotic treatment of urinary tract infection (UTI) in acutely unwell young children presenting to primary care. METHODS: Decision analytic model synthesising data from a multicentre, prospective cohort study (DUTY) and the wider literature to estimate the short-term and lifetime costs and healthcare outcomes (symptomatic days, recurrent UTI, quality adjusted life years) of eight diagnostic strategies. We compared GP clinical judgement with three strategies based on a 'coefficient score' combining seven symptoms and signs independently associated with UTI and four strategies based on weighted scores according to the presence/absence of five symptoms and signs. We compared dipstick testing versus laboratory culture in children at intermediate risk of UTI. RESULTS: Sampling, culture and antibiotic costs were lowest in high-specificity DUTY strategies (£1.22 and £1.08) compared to clinical judgement (£1.99). These strategies also approximately halved urine sampling (4.8% versus 9.1% in clinical judgement) without reducing sensitivity (58.2% versus 56.4%). Outcomes were very similar across all diagnostic strategies. High-specificity DUTY strategies were more cost-effective than clinical judgement in the short- (iNMB = £0.78 and £0.84) and long-term (iNMB =£2.31 and £2.50). Dipstick tests had poorer cost-effectiveness than laboratory culture in children at intermediate risk of UTI (iNMB = £-1.41). CONCLUSIONS: Compared to GPs' clinical judgement, high specificity clinical rules from the DUTY study could substantially reduce urine sampling, achieving lower costs and equivalent patient outcomes. Dipstick testing children for UTI is not cost-effective.

Promoting health and reducing costs: a role for reform of self-monitoring of blood glucose provision within the National Health Service.

AIM: To determine the cost-effectiveness of all options for the self-monitoring of blood glucose funded by the National Health Service, providing guidance for disinvestment and testing the hypothesis that advanced meter features may justify higher prices. METHODS: Using data from the Health and Social Care Information Centre concerning all 8 340 700 self-monitoring of blood glucose-related prescriptions during 2013/2014, we conducted a cost-minimization analysis, considering both strip and lancet costs, including all clinically equivalent technologies for self-monitoring of blood glucose, as determined by the ability to meet ISO-15197:2013 guidelines for meter accuracy. RESULTS: A total of 56 glucose monitor, test strip and lancet combinations were identified, of which 38 met the required accuracy standards. Of these, the mean (range) net ingredient costs for test strips and lancets were £0.27 (£0.14-£0.32) and £0.04 (£0.02-£0.05), respectively, resulting in a weighted average of £0.28 (£0.18-£0.37) per test. Systems providing four or more advanced features were priced equal to those providing just one feature. A total of £12 m was invested in providing 42 million self-monitoring of blood glucose tests with systems that fail to meet acceptable accuracy standards, and efficiency savings of £23.2 m per annum are achievable if the National Health Service were to disinvest from technologies providing lesser functionality than available alternatives, but at a much higher price. CONCLUSION: The study uncovered considerable variation in the price paid by the National Health Service for self-monitoring of blood glucose, which could not be explained by the availability of advanced meter features. A standardized approach to self-monitoring of blood glucose prescribing could achieve significant efficiency savings for the National Health Service, whilst increasing overall utilisation and improving safety for those currently using systems that fail to meet acceptable standards for measurement accuracy.

Is a chlorhexidine reaction test better than dipsticks to detect asymptomatic bacteriuria in pregnancy?

Detection of asymptomatic bacteriuria (ASB) in pregnancy is important to avert the attendant morbidities. Therefore, we assessed the use of chlorhexidine reaction to detect ASB in pregnancy. This was a prospective study, which compared chlorhexidine reaction with dipstick tests and urine culture in 150 asymptomatic pregnant women. Urine cultures detected bacteriuria in seven women (4.7%). Chlorhexidine detected ASB in 72 women (48%) and had sensitivity, specificity and accuracy of 100%, 54% and 56%, respectively. Leucocyte esterase (LE) and nitrite detected bacteriuria in 31 (20.7%) women and 12 (8.0%) women, respectively. Singly, LE had a sensitivity and specificity of 14.3% and 79%, respectively, while nitrite's sensitivity and specificity was 42.9% and 93.7%, respectively. Combined, LE and nitrite had better sensitivity (97.9%) and accuracy (94%). Since the accuracy of chlorhexidine is low, other than urine culture, combined dipstick urinalysis of leucocyte esterase and nitrite tests is good to detect asymptomatic bacteriuria in pregnancy.

Development of a manual self-assembled colloidal gold nanoparticle-immunochromatographic strip for rapid determination of human interferon-γ.

Interferons (IFNs) play a role in inhibition of tumor growth and participate in immunoreactions. Among IFNs, interferon-γ (IFNγ) is one of the most important therapeutic proteins and its immunodulation ability is better than that of other types. The objective of this study is to develop a manual self-assembled colloidal gold nanoparticle-immunochromatographic strip for human IFNγ using anti-human IFNγ polyclonal and monoclonal antibodies. Colloidal gold with a 25 nm diameter was made from chloroauric acid (HAuCl4), and labeled on anti-IFNγ mAbs as a chrominance reagent. A good linear relationship existed between the pixel intensity and the human IFNγ concentrations from 10-1000 ng mL(-1) in mouse serum and buffer, respectively, the regression equation was Y = 0.159logX + 0.0648, R(2) = 0.992 in mouse serum; Y = 0.294logX + 0.091, R(2) = 0.9969 in phosphate buffer by this proposed strip. Moreover, in the determination for mouse serum samples no cross-reaction occurred and the detection time was approximately 10 minutes. The shelf life of the strip was above 28 days at room temperature. The major advantages of the manual operation model were no expensive instruments and less reagents required. This proposed strip was highly specific, economic, convenient, and no machine was needed in clinical diagnosis.

Diagnostic accuracy of urine dipstick testing in screening for microalbuminuria in type 2 diabetes: a cohort study in primary care.

BACKGROUND: Clinical guidelines recommend annual screening for microalbuminuria in diabetes. Detection of microalbuminuria is important because it is associated with increased morbidity and mortality. Dipstick tests for microalbuminuria may be convenient, but their accuracy is uncertain. OBJECTIVE: To assess the utility of urine dipstick testing for microalbuminuria in type 2 diabetes. METHODS: In a 6-week cohort study in four general practices in Oxfordshire, UK, first-pass urine samples were obtained at two weekly intervals from patients with type 2 diabetes and tested in the practice using Micral-Test and Microalbustix urine dipsticks. Parallel samples were sent for laboratory albumin-creatinine ratio (ACR) assay. Results of single dipstick tests and sequences of dipstick and laboratory tests were compared with a clinical testing strategy based on current guidelines to assess the accuracy and estimate costs of testing. RESULTS: The prevalence of microalbuminuria was 12.5% (n = 88). Mean (standard deviation) age was 68 (10) years, 56 (57%) were men. Median (interquartile range) diabetes duration was 6.2 (2.0-10.0) years. The sensitivity and specificity, respectively, of a single Micral-Test were 91.7% and 44.0% and of a Microalbustix test 33.3% and 92.0%. Testing strategies involving dipstick and laboratory ACR measurements or dipstick tests had similar accuracy. The costs of using dipstick tests were overall lower than laboratory ACR-based testing. CONCLUSIONS: Dipstick testing in this study did not reliably identify diabetes patients with microalbuminuria. Although dipstick testing would decrease testing costs, it could either fail to diagnose most patients with microalbuminuria or increase the numbers of patients retested depending on the dipstick used.

Self-monitoring of blood glucose in Type 2 diabetes: cross-sectional analyses in 1993, 1999 and 2009.

AIM: To characterize the numbers of reagent strips dispensed for self-monitoring of blood glucose to patients with Type 2 diabetes in Tayside, Scotland, in 1993, 1999 and 2009. METHODS: A diabetes clinical information system in Tayside, record-linked to electronic dispensed prescribing records, was used to collate all dispensed prescribing records for three cross-sectional samples of patients with Type 2 diabetes in 1993 (n = 5728), 1999 (n = 8109) and at 1 January 2009 (n = 16,450). The numbers of reagent strips dispensed during the relevant calendar year were calculated and patients stratified by treatment. We also explored whether age, sex or material and social deprivation were associated with whether a patient received strips. RESULTS: Proportions of people who received self-monitoring reagent strips increased from 15.5% in 1993, to 24.2% in 1999 to 29.8% in 2009, as did numbers of strips dispensed. While the proportion of diet-treated patients who received reagent strips was still very low in 2009 (5.6%), the proportion among those treated with oral agents tripled from 9.4 to 27.4% between 1993 and 2009. Over 90% of patients treated with insulin received reagent strips and, among non-insulin-treated patients, this was more common among women, younger people and less deprived groups. CONCLUSIONS: The numbers of reagent strips dispensed for self-monitoring of blood glucose has increased and almost all insulin-treated patients receive strips. While few diet-treated patients receive strips, they are more extensively dispensed to those treated with oral agents. Given that self-monitoring of blood glucose is no longer routinely recommended in non-insulin treated patients, strategies to reduce unnecessary dispensing of reagent strips are needed.

Regional differences in sales of glucometer strips and antidiabetics.

BACKGROUND: Studies have shown that the prevalence of diabetes in Norway is 3-5 %, and that approximately 97,000 Norwegian patients perform self-monitoring of blood glucose. There is a need for studies of geographical differences in diabetes prevalence and treatment. This study investigates differences between counties in the prevalence of patients treated with antidiabetics in Norway, and in the use of glucometer strips. MATERIAL AND METHOD: Data on the sale of antidiabetes medication to non-institutionalized patients were acquired from the Norwegian Register of Prescriptions, while corresponding data on glucometer strips were received from the Norwegian Health Economics Administration (HELFO). RESULTS: We found a nationwide prevalence of medicinally treated diabetes of 2.9 %. The corresponding prevalence of use of glucometer strips was 2.1 %. There was a 27.5 % difference between the counties with the highest and lowest prevalence of medicinally treated diabetes, while the difference in use of glucometer strips was 31.5 %. The average cost of antidiabetes drugs was 23.7 % higher in the county with the highest average expenditure compared with the county with the lowest expenditure. There was a difference of up to 44 % between counties in the average purchase of glucometer strips per person. INTERPRETATION: The geographical differences may be due to different availability of health services or different therapy traditions. A shortage of guidelines on the frequency of self-monitoring of blood glucose may also have a bearing on the differences.

The impact of non-severe hypoglycemic events on work productivity and diabetes management.

OBJECTIVES: Hypoglycemia is a common complication of treatment with certain diabetes drugs. Non-severe hypoglycemic events (NSHEs) occur more frequently than severe events and account for the majority of total events. The objective of this multi-country study was to identify how NSHEs in a working population affect productivity, costs, and self-management behaviors. METHODS: A 20-minute survey assessing the impact of NSHEs was administered via the Internet to individuals (≥ 18 years of age) with self-reported diabetes in the United States, United Kingdom, Germany, and France. The analysis sample consisted of all respondents who reported an NSHE in the past month. Topics included: reasons for, duration of, and impact of NSHE(s) on productivity and diabetes self-management. RESULTS: A total of 1404 respondents were included in this analysis. Lost productivity was estimated to range from $15.26 to $93.47 (USD) per NSHE, representing 8.3 to 15.9 hours of lost work time per month. Among individuals reporting an NSHE at work (n = 972), 18.3% missed work for an average of 9.9 hours (SD 8.4). Among respondents experiencing an NSHE outside working hours (including nocturnal), 22.7% arrived late for work or missed a full day. Productivity loss was highest for NSHEs occurring during sleep, with an average of 14.7 (SD 11.6) working hours lost. In the week following the NSHE, respondents required an average of 5.6 extra blood glucose test strips. Among respondents using insulin, 25% decreased their insulin dose following the NSHE. CONCLUSIONS: NSHEs are associated with substantial economic consequences for employers and patients. Greater attention to treatments that reduce NSHEs could have a major, positive impact on lost work productivity and overall diabetes management.

Tetanus Quick Stick as an applicable and cost-effective test in assessment of immunity status.

INTRODUCTION: Tetanus vaccine and immunoglobulin administration are challenging decisions mostly because of the fact that the current protocol for immunization against tetanus is based on 2 variables: the vaccination status of the patient and the nature of wound and its exposure. To solve this problem, Tetanus Quick Stick (TQS; Nephrotek Laboratory, Rungis, France), an immunochromatographic dipstick test, was developed to determine the tetanus immunity of the patients. The aim of this present study was to investigate the sensitivity, specificity, and the positive and negative predictive values and cost-effectiveness of TQS in the emergency department (ED) setting. METHODS: Blood samples were collected from 200 patients presenting to our ED. Information including demographic information, tetanus immunization status, wound description, and the preventive measures taken by the emergency physician were gathered by a preeducated nurse. Tetanus Quick Stick test and enzyme-linked immunosorbent assay were performed as the standard diagnostic test by an emergency physician and a laboratory technician, respectively; and results of the 2 techniques were compared. RESULT: Overall, tetanus vaccine was administered to 141(70.5%) patients and immunoglobulin to 105 (52.5%) patients. The analysis revealed 88.1% sensitivity and 97.6% specificity for the TQS test. The positive and negative predictive values of TQS test were 99.3% and 66.1%, respectively. Our analysis is also showed a significant decrease in cost when TQS was applied for patients with dirty, tetanus prone wounds or injuries and unknown or incomplete vaccination history (€ 9.48 versus € 12.1). CONCLUSION: This study revealed TQS test to be appropriate and cost-effective for ED use especially in evaluating patients who do not remember or cannot give their tetanus immunization history.

Comparison of one-year costs of type 2 diabetes treatment with insulin glargine or insulin detemir in a basal supported oral therapy (BOT) in Germany.

OBJECTIVE: A one-year cost analysis comparing basal insulin analogues glargine (IG, Lantus) versus detemir (ID, Levemir) in combination with oral antidiabetic drugs (basal supported oral therapy; BOT) in insulin naive Type 2 diabetes patients in Germany based on the results of a randomized controlled clinical trial (RCT). The trial demonstrated equivalent treatment efficacy. MATERIALS AND METHODS: Total direct diabetes treatment costs were estimated from the perspective of the German statutory health insurance (SHI) for the time horizon of one-year. Simulated resources included medication (insulin, oral antidiabetic drugs) and consumable items (needles, blood glucose test strips and lancets). Initial and final insulin doses per kg body weight and proportion of patients with once/twice daily insulin injection were taken from the above mentioned RCT. Unit costs were taken from official German price lists and sources. Deterministic-(DTA) and probabilistic sensitivity analyses (PSA) on resource use and unit costs were performed to test robustness of the results. RESULTS: Average annual treatment costs per patient (base case) were euro 849 for glargine and euro 1,334 for detemir resulting in cost savings of euro 486 per patient per year (36%). Costs of insulins were euro 469 (IG) and euro 746 (ID). Costs of consumable items amounted at euro 380 (IG) and euro 588 (ID) respectively. Sensitivity analyses confirmed the findings in favor of insulin glargine. PSA results found cost savings ranging from euro 429 to euro 608 (5th/95th percentiles). CONCLUSIONS: The current model estimated that insulin glargine was associated with lower annual treatment costs of euro 486 (36%) compared to the use of insulin detemir while the same glycemic control is expected to be achieved.

Emerging design strategies for constructing multiplex lateral flow test strip sensors.

Conventional lateral flow test strip (LFTS) sensors are insufficiently accurate and reliable due to their single-target detection with limited sample information in a single test. The increasing demand for the simultaneous determination of multiple analytes has recently been accelerating the rapid development of high-throughput and multiplexed LFTS sensing technologies. In this contribution, we systematically summarize the recent achievements on the design, development, and application of multiplexed LFTS sensors for improved rapid on-site diagnostics. The discussion focuses on emerging design strategies to increase multiplexing capacity for enhancing analytical efficiency and precision. As a proof-of-concept, several typical examples are presented. The advantages and disadvantages of such approaches are critically analyzed. Finally, we briefly discuss the current challenges and future perspectives.

A cost-effective screening method for preoperative hyperglycemia.

INTRODUCTION: The preoperative encounter may offer a cost-effective opportunity for diabetes screening. METHODS: Three hundred forty-seven fasting patients had a preoperative glucose measurement determined from blood residue left on the IV needle, measured with an Accu-Chek glucometer (Roche Diagnostics, Indianapolis, IN). RESULTS: After excluding patients with a diabetes history, 4.0% had a glucose measurement between 100 and 125 mg/dL, at a cost of $14.22 per identification, and 1.2% had a glucose measurement more than 125 mg/dL, at a cost of $32.00 per identification. CONCLUSIONS: This preoperative blood glucose screening test was implemented at a cost of approximately one-tenth of current methods.

Evaluation of the ARKRAY AUTION Eleven reflectometer in detecting microalbuminuria with AUTION Screen test strips and proteinuria with AUTION Sticks 10PA strips.

OBJECTIVE: Albumin/creatinine and protein/creatinine ratios were measured with the ARKRAY AUTION Eleven reflectometer using AUTION Screen and AUTION Sticks 10PA strips, respectively, against quantitative Siemens Advia reference procedures from 368 patient urines, as an evaluation of their applicability for use in points-of-care and small laboratories. MATERIAL AND METHODS: Direct reflectance measurements were utilized to estimate imprecision, as well as to suggest reclassification of ordinal scale categories into normoalbuminuria, microalbuminuria and macroalbuminuria groups (3.4 g/mol and 34 g/mol cut-off limits, corresponding to 30 mg/g and 300 mg/g creatinine in conventional units). RESULTS: Analytically, ordinal scale albumin/creatinine ratios agreed in 86% of cases with those obtained from Advia measurements, resulting in a kappa coefficient of 0.79. Protein/creatinine ratios of the AUTION Sticks 10PA strip were classified into three groups at limits of 11.3 g/mol and 56.6 g/mol (100 mg/g and 500 mg/g in conventional units), with an agreement of 77% and a kappa coefficient of 0.65 against Advia procedures. To optimize clinical outcomes, cut-off reflectances of ordinal scale categories of AUTION Eleven were adjusted. The clinical specificity of detecting an increased albumin/creatinine ratio was then increased from 81% to 95%, with clinical sensitivity kept at 88% at the 3.4 g/mol limit of the reference procedure. Clinical specificity of the albuminuria field alone (at a clinical sensitivity of 88%) was only 73%. Adjustments to cut-off reflectances of the reported categories for protein/creatinine ratios increased clinical specificity from 54% to 94%, while losing clinical sensitivity from 97% to 89% only, with an improved concordance of 83% and a kappa coefficient of 0.75 against Advia measurements. The combination to creatinine measurements improved clinical specificity compared to 50% by the protein field alone. In economic terms, it is estimated that population screening for microalbuminuria using the AUTION Eleven reflectometer is cheaper than by quantitative albumin/creatinine measurements alone, based on the incidence of end-stage renal disease of 90 patients/million/year at the Northern Ostrobothnia Hospital District.