A prospective, randomized, controlled, double-blind, multi-center study to evaluate the efficacy and safety of a blue light device for the treatment of chronic back pain.

Introduction: Chronic back pain is one of the most prevalent conditions and has a large socio-economic impact. The lack of routine use of non-pharmacological options and issues associated with pharmacological treatments underscore high unmet needs in the treatment of back pain. Although blue light phototherapy has proven efficacy in dermatology, limited information is available about its use in back pain. Methods: In this proof-of-concept, randomized controlled trial, a pain relief patch (PRP) delivered blue light at the site of back pain for 30 min during five treatment sessions. The comparator device delivered green light for 5 s but was worn for 30 min. A follow-up visit took place after the last treatment. The primary objective was to demonstrate the superiority of treatment by PRP, compared to the control device, in reducing pain intensity at the end of the treatment period. The post-treatment visual analog scale (VAS) pain intensity score for each group was calculated across the five treatment sessions and compared to the baseline. Secondary objectives included the disability score (Roland-Morris Disability Questionnaire) and safety. Results: The full analysis set included 171 patients. A statistically significant reduction in pain intensity occurred after the use of PRP (p < 0.02), but the study did not meet its primary objective of a superiority trial aimed at demonstrating a 0.6 cm difference in favor of PRP on the VAS scale. There was no significant change in the disability scores. Subgroup analyses were performed to identify the treatment response by patient characteristics such as pain intensity at baseline and skin type. As expected, safety data showed erythema and skin discoloration in the PRP group but not in the control group. Discussion/conclusion: This trial had multiple limitations that need to be addressed in future research. Although the primary objective was not achieved, this proof-of-concept study provides important efficacy and safety data in relation to the use of blue light in the treatment of chronic back pain and key insights that may support further research on similar devices. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01528332.

Is exhaled carbon monoxide level associated with blood glucose level? A comparison of two breath analyzing methods.

The level of exhaled carbon monoxide (eCO) is considered a marker of oxidative stress in diabetes. Previous findings indicated that eCO levels correlated with blood glucose level. The aim of this work was to apply and compare two independent analyzing methods for eCO after oral glucose administration. Glycemia, eCO, and exhaled hydrogen were measured before and after oral administration of glucose. Six healthy nonsmoking volunteers participated. For eCO analysis, we used two methods: a commercially available electrochemical sensor, and a high-precision laser spectrometer developed in our laboratory. The precision of laser-spectroscopic eCO measurements was two orders of magnitude better than the precision of the electrochemical eCO measurement. eCO levels measured by laser spectrometry after glucose administration showed a decrease of 4.1%+/-1.5% compared to the baseline (p<0.05). Changes in the eCO measured by the electrochemical sensor were not significant (p=0.08). Exhaled hydrogen levels increased by 40% within the first 10 min after glucose administration (p<0.05). The previous finding that the glycemia increase after glucose administration was associated with a significant increase in eCO concentrations was not confirmed. We propose that previous eCO measurements with electrochemical sensors may have been affected by cross sensitivity to hydrogen.

Time resolved simultaneous detection of 14NO and 15NO via mid-infrared cavity leak-out spectroscopy.

We present a ring-down absorption spectrometer based on a continuous-wave CO laser in the mid-infrared spectral region near lambda = 5 microm. Using a linear ring-down cavity (length: 0.5 m) with high reflective mirrors (R = 99.988 %), we observed a noise-equivalent absorption coefficient of 3 x 10(-10) cm(-1)Hz(-1/2). This corresponds to a noise-equivalent concentration of 800 parts per trillion (ppt) for (14)NO and 40 ppt for (15)NO in 1 s averaging time. We achieve a time resolution of 1 s which allows time resolved simultaneous detection of the two N isotopes. The delta(15)N value was obtained with a precision of +/-1.2 per thousand in a sample with a NO fraction of 11 ppm. The simultaneous detection enables the use of (15)NO as a tracer molecule for endogenous biomedical processes.

Online recording of ethane traces in human breath via infrared laser spectroscopy.

A method is described for rapidly measuring the ethane concentration in exhaled human breath. Ethane is considered a volatile marker for lipid peroxidation. The breath samples are analyzed in real time during single exhalations by means of infrared cavity leak-out spectroscopy. This is an ultrasensitive laser-based method for the analysis of trace gases on the sub-parts per billion level. We demonstrate that this technique is capable of online quantifying of ethane traces in exhaled human breath down to 500 parts per trillion with a time resolution of better than 800 ms. This study includes what we believe to be the first measured expirograms for trace fractions of ethane. The expirograms were recorded after a controlled inhalation exposure to 1 part per million of ethane. The normalized slope of the alveolar plateau was determined, which shows a linear increase over the first breathing cycles and ends in a mean value between 0.21 and 0.39 liter-1. The washout process was observed for a time period of 30 min and was modelled by a threefold exponential decay function, with decay times ranging from 12 to 24, 341 to 481, and 370 to 1770 s. Our analyzer provides a promising noninvasive tool for online monitoring of the oxidative stress status.

Exercise in closed-loop control: a major hurdle.

BACKGROUND: People with type 1 diabetes mellitus (T1DM) are at risk for exercise-induced hypoglycemia. Prevention of such hypoglycemia in a closed-loop setting is a major challenge. Markers for automated detection of physical activity could be heart rate (HR) and body acceleration counts (AC). Correlations between HR, AC, and glucose concentrations before and after moderate intensity exercise were examined in T1DM patients during open- loop control. METHOD: Eleven T1DM subjects treated with an insulin pump performed moderate intensity exercise of 30 min. Glucose profiles, insulin concentrations, HR, and acceleration were measured. RESULTS: Mean (range) glucose decrease during exercise was 1.4 (0 to 3.3) mmol/liter. The mean increase in HR was 45.2 beats per minutes (15 to 106 bpm). Mean increase in AC was 18,000 (3,000 to 25,000). No correlations were seen between the glucose drop and HR or AC. A trend was observed between the increase in HR and increase in AC. CONCLUSION: Moderate intensity exercise resulted in increased HR and body AC while it decreased glucose concentrations but, in this real-time setting, no association could be demonstrated between the glucose decrease and increase in HR or AC.

Future acceptance of an artificial pancreas in adults with type 1 diabetes.

BACKGROUND: The purpose of this study was to examine future acceptance of an artificial pancreas (AP) and its perceived usefulness, ease of use, and trust in the device. METHODS: A questionnaire, based on the Technology Acceptance Model, was developed to examine future acceptance with its determinants and intention to use the AP. One hundred thirty-two patients with diabetes type 1 treated with insulin pump therapy completed the questionnaire. Using factor analysis and reliability analysis, the number of items was reduced from 34 to 15. RESULTS: The response rate was 66%. The subjects had a mean age of 43 years, and 34% were male. Almost 75% had the intention to use an AP. There were high scores on perceived usefulness (expected improvement of glucose control: 35.6% moderately agreed and 53% strongly agreed), perceived ease of use (expectation that the AP can be easily handled: 33.3% moderately agreed and 53.8% strongly agreed), and trust (administration of correct insulin dose and reliability of glucose measurement: 40.9% and 38.9% moderately agreed, whereas 32.6% and 28.2% strongly agreed, respectively). CONCLUSIONS: A newly developed questionnaire examining the acceptance of an AP indicated that most patients with continuous subcutaneous insulin infusion-treated type 1 diabetes have the intention to use an AP system and have a positive attitude toward perceived usefulness, ease of use, and trust.

Quantifying the composition of human skin for glucose sensor development.

BACKGROUND: Glucose is heterogeneously distributed within human skin. In order to develop a glucose measurement method for human skin, both a good quantification of the different compartments of human skin and an understanding of glucose transport processes are essential. This study focused on the composition of human skin. In addition, the extent to which intersubject variability in skin composition alters glucose dynamics in human skin was investigated. METHODS: To quantify the composition of the three layers of human skin-epidermis, dermis, and adipose tissue-cell and blood vessel volumes were calculated from skin biopsies. These results were combined with data from the literature. The composition was applied as input for a previously developed computational model that calculates spatiotemporal glucose dynamics in human skin. The model was used to predict the physiological effects of intersubject variability in skin composition on glucose profiles in human skin. RESULTS: According to the model, the lag time of glucose dynamics in the epidermis was sensitive to variation in the volumes of interstitial fluid, cells, and blood of all layers. Data showed most variation/uncertainty in the volume composition of the adipose tissue. This variability mainly influences the dynamics in the adipose tissue. CONCLUSIONS: This study identified the intersubject variability in human skin composition. The study shows that this variability has significant influence on the glucose dynamics in human skin. In addition, it was determined which volumes are most critical for the quantification and interpretation of measurements in the different layers.

Patients' perception and future acceptance of an artificial pancreas.

BACKGROUND: Little is known of patient acceptance of an artificial pancreas (AP). The purpose of this study was to investigate future acceptance of an AP and its determinants. METHODS: Patients with type 1 diabetes treated with insulin pump therapy were interviewed using questions based on the technology acceptance model and completed the diabetes treatment and satisfaction questionnaire (DTSQ). RESULTS: Twenty-two adults with type 1 diabetes participated. Half of the patients were followed in a university hospital, and the others were under treatment in an affiliated teaching hospital. Half of the patients were male. The mean DTSQ score was 29 (range 23-33). The AP was perceived as likely to be useful. Perceived advantages were a stable glucose regulation, less need for self-monitoring of blood glucose, relief of daily concerns, and time saving. Participants were confident in their capability to use the system. Although many participants (58%) had been reluctant to start continuous subcutaneous insulin infusion, the majority (79%) felt they would have no barriers to start using the AP. Trust in the AP was related to the quality of glucose control it would provide. Almost everyone expressed the intention to use the new system when available, even if it would initially not cover 24/24 hours. CONCLUSION: The overall attitude on the AP was positive. Intention to use was dependent on trust in the AP, which was related to the quality of glucose control provided by the AP.

Parts per trillion sensitivity for ethane in air with an optical parametric oscillator cavity leak-out spectrometer.

Spectroscopic detection of ethane in the 3-microm wavelength region was performed by means of a cw optical parametric oscillator and cavity leak-out. We achieved a minimum detectable absorption coefficient of 1.6 x 10(-10) cm 1/square root of Hz, corresponding to an ethane detection limit of 6 parts per trillion/square root of Hz. For 3-min integration time the detection limit was 0.5 parts per trillion. The levels are to our knowledge the best demonstrated so far. These frequency-tuning capabilities facilitated multigas analysis with simultaneous monitoring of ethane, methane, and water vapor in human breath.