Severely increased albuminuria in patients with type 2 diabetes mellitus is associated with increased subclinical atherosclerosis in femoral arteries with Na [18F]F activity as a proxy - The DETERMINE study.

BACKGROUND AND AIMS: Sodium [18F]fluoride (Na [18F]F) positron emission tomography imaging allows detailed visualization of early arterial micro-calcifications. This study aims to investigate atherosclerosis manifested by micro-calcification, macro-calcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria and severely decreased kidney function. METHODS: A cohort was stratified in four groups (N = 10 per group), based on KDIGO categories (G1-5 A1-3). G1-2A1 non-diabetic controls (median [IQR] estimated glomerular filtration rate (eGFR) in mL/min/1.73 m2 91 [81-104]), G1-2A1 with T2DM (eGFR 87 [84-93], and albumin-creatinin-ratio (ACR) in mg/mmol 0.35 [0.25-0.75]), G1-2A3 with T2DM (eGFR 85 [60-103], and ACR 74 [62-122], and G4A3 with T2DM (eGFR 19 [13-27] and ACR 131 [59-304]). RESULTS: Na [18F]F femoral artery grading score differed significantly in the groups with the highest Na [18F]F activity in A3 groups with T2DM (G1-2A3 with T2DM 228 [100-446] and G4A3 with T2DM 198 [113-578]) from the lowest groups of the G1-2A1 with T2DM (33 [0-93]) and in G1-2A1 non-diabetic controls (75 [0-200], p = 0.001). Aortic Na [18F]F activity and femoral artery computed tomography (CT)-assessed macro-calcification was increased in G4A3 with T2DM compared with G1-2A1 with T2DM (47.5 [33.8-73.8] vs. 17.5 [8.8-27.5] (p = 0.006) and 291 [170-511] vs. 12.2 [1.41-44.3] mg (p = 0.032), respectively). Carotid-femoral pulse wave velocity (PWV)-assessed aortic stiffness was significantly higher in both A3 groups with T2DM compared with G1-2A1 with T2DM (11.15 and 12.35 vs. 8.86 m/s, respectively (p = 0.009)). CONCLUSIONS: This study indicates that the presence of severely increased albuminuria in patients with T2DM is cross-sectionally associated with subclinical arterial disease in terms of micro-calcification and aortic stiffness. Additional decrease in kidney function was associated with advanced macro-calcifications.

Model and Empirical Data-Based Cost-Utility Studies of Continuous Glucose Monitoring in Individuals with Type 1 Diabetes: A Protocol of a Systematic Review on Methodology and Quality.

INTRODUCTION: This review aims to critically appraise differences in methodology and quality of model-based and empirical-data-based cost-utility studies to address key limitations, opportunities, and challenges to inform future cost-utility analyses of continuous glucose monitoring (CGM) in type 1 diabetes. This protocol is registered at PROSPERO (CRD42023391284). METHODS: The review will be conducted in accordance with the PRISMA guideline for systematic reviews. Searches will be conducted in MEDLINE, Embase, Web of Science, Cochrane Library, and Econlit from 2000 to January 2023. Model and empirical data-based studies evaluating the cost-utility of any CGM system in type 1 diabetes will be considered for inclusion. Studies that only report on cost per life year or any other clinical outcome, or reporting only costs or only clinical outcomes studies in type 2 diabetes populations, and studies on bi-hormonal closed loops and do-it-yourself hybrid closed loop devices will be excluded. Two reviewers will independently screen each study for inclusion. Data on the intervention, population, model settings (such as perspective, time horizon), model type and structure, clinical outcomes used to populate the model, validation, and uncertainty will be extracted and qualitatively synthesised. Quality will be assessed using the Philips et al. 2006 (model-based studies) or Consensus Health Economic Criteria (empirical data-based studies) checklists. Model validation will be assessed using the AdViSHE checklist. DISCUSSION: Now that CGM is being used more broadly in practice, critical appraisal of existing cost-utility methodology and quality is important to inform future cost-utility analyses of CGM in type 1 diabetes in various settings.

Prevalence of scoliosis and impaired pulmonary function in patients with type III osteogenesis imperfecta.

PURPOSE: Osteogenesis Imperfecta (OI) is a rare group of congenital genetic disorders that consists of a collagen synthesis defect. The most severe phenotype is type III OI. Characterized by progressive bone deformity, fragility and pulmonary impairment, causing significant morbidity and mortality. Also, multilevel spine deformities are observed, such as scoliosis. The literature on the pathophysiology of pulmonary impairment in relation to scoliosis in these patients is scarce and conflicting. This study aims to determine the prevalence of scoliosis and its relation to pulmonary function in type III OI patients. METHODS: This retrospective cohort study took place between April 2020 and November 2021. Forty-two patients with type III OI were included. Anterior-posterior spine radiographs were evaluated for scoliosis. Pulmonary function was assessed using spirometry and partial pressure of carbon dioxide. RESULTS: All 42 patients had scoliosis, with a mean curve of 66° (95% CI of range). Vital lung capacity was decreased, compared to a non-OI population (mean 1.57 L). This was correlated to the degree of scoliosis (st. ß - 0.40, P = 0.03), especially in increasing thoracic curves. Restrictive lung pathophysiology was shown in our study population with a mean FEV1/FVC ratio of 0.85. CONCLUSIONS: Increasing thoracic scoliosis was correlated with decreased vital lung capacity in our study population of type III OI patients. High FEV1/FVC ratios found in this study population show restrictive lung pathophysiology. Therefore, it is plausible that the pulmonary impairment found in type III OI patients is a combined issue, partly associated to scoliosis and partly intrinsic to OI.

Prognostic model for predicting survival in very preterm infants: an external validation study.

OBJECTIVE: To perform a temporal and geographical validation of a prognostic model, considered of highest methodological quality in a recently published systematic review, for predicting survival in very preterm infants admitted to the neonatal intensive care unit. The original model was developed in the UK and included gestational age, birthweight and gender. DESIGN: External validation study in a population-based cohort. SETTING: Dutch neonatal wards. POPULATION OR SAMPLE: All admitted white, singleton infants born between 23+0 and 32+6 weeks of gestation between 1 January 2015 and 31 December 2019. Additionally, the model's performance was assessed in four populations of admitted infants born between 24+0 and 31+6 weeks of gestation: white singletons, non-white singletons, all singletons and all multiples. METHODS: The original model was applied in all five validation sets. Model performance was assessed in terms of calibration and discrimination and, if indicated, it was updated. MAIN OUTCOME MEASURES: Calibration (calibration-in-the-large and calibration slope) and discrimination (c statistic). RESULTS: Out of 6092 infants, 5659 (92.9%) survived. The model showed good external validity as indicated by good discrimination (c statistic 0.82, 95% CI 0.79-0.84) and calibration (calibration-in-the-large 0.003, calibration slope 0.92, 95% CI 0.84-1.00). The model also showed good external validity in the other singleton populations, but required a small intercept update in the multiples population. CONCLUSIONS: A high-quality prognostic model predicting survival in very preterm infants had good external validity in an independent, nationwide cohort. The accurate performance of the model indicates that after impact assessment, implementation of the model in clinical practice in the neonatal intensive care unit could be considered. TWEETABLE ABSTRACT: A high-quality model predicting survival in very preterm infants is externally valid in an independent cohort.

Hyperacusis in tinnitus patients relates to enlarged subcortical and cortical responses to sound except at the tinnitus frequency.

Hyperacusis, a hypersensitivity to sounds of mild to moderate intensity, has been related to increased neural gain along the auditory pathway. To date, there is still uncertainty on the neural correlates of hyperacusis. Since hyperacusis often co-occurs with hearing loss and tinnitus, the effects of the three conditions on cortical and subcortical structures are often hard to separate. In this fMRI study, two groups of hearing loss and tinnitus participants, with and without hyperacusis, were compared to specifically investigate the effect of the latter in a group that often reports hyperacusis. In 35 participants with hearing loss and tinnitus, with and without hyperacusis as indicated by a cut-off score of 22 on the Hyperacusis Questionnaire (HQ), subcortical and cortical responses to sound stimulation were investigated. In addition, the frequency tuning of cortical voxels was investigated in the primary auditory cortex. In cortical and subcortical auditory structures, sound-evoked activity was higher in the group with hyperacusis. This effect was not restricted to frequencies affected by hearing loss but extended to intact frequencies. The higher subcortical and cortical activity in response to sound thus appears to be a marker of hyperacusis. In contrast, the response to the tinnitus frequency was reduced in the group with hyperacusis. This increase in subcortical and cortical activity in hyperacusis can be related to an increase in neural gain along the auditory pathway, and the reduced response to the tinnitus frequency to differences in attentional resources allocated to the tinnitus sound.

Optimizing surgery of metaphyseal-diaphyseal fractures of the fifth metatarsal: a cadaveric study on implications of intramedullary screw position, screw parameters and surrounding anatomic structures.

AIMS: Many advocate screw fixation of fractures to the metaphyseal-diaphyseal junction of the fifth metatarsal base, better known as Jones fractures (JF), to facilitate quicker ambulation and return to sport. Maximizing screw parameters based on fifth metatarsal (MT5) anatomy, alongside understanding the anatomic structures compromised by screw insertion, may optimize surgical outcomes. This study aims to (1) correlate the proximity of JF to the peroneus brevis (PB) and plantar fascia (PF) footprints and (2) quantify optimal screw parameters given MT5 anatomy. MATERIALS AND METHODS: 3D CT-scan reconstructions were made of 21 cadaveric MT5s, followed by meticulous mapping of the PB and PF onto the reconstructions. Based on bone length, shape, narrowest intramedullary canal (IMC) diameter, and surrounding anatomy, two traditional debated screw positions were modeled for each reconstruction: (1) an anatomically positioned screw (AP), predicated on maximizing screw length by following the IMC for as long as possible, and (2) a clinically achievable screw (CA), predicated on maximizing screw length without violating the fifth tarso-metatarsal joint or adjacent cuboid bone. Fixation parameters were calculated for all models. RESULTS: The PB and PF extended into the JF site in 29% and 43%, respectively. AP's did not affect PB and PF footprint but required screw entry through the cuboid and fifth tarso-metatarsal joint in all specimens. CA screw entry sites, avoiding the cuboid and fifth tarso-metatarsal joint, partially compromised the PB and PF insertions in 33% and 62% with a median surface loss of 1.6%%(range 0.2-3.2%) and 0.81%%(range 0.05-1.6%), respectively. Mean AP screw length was 64±3.6mm and thread length 49±4.2mm. Mean CA screw length was 48±5.8mm and thread length 28±6.9mm. CONCLUSION: This study underscores the challenges associated with surrounding MT5 anatomy as they relate to optimal JF treatment. Both the extent of JF as well as a clinically achievable positioned screw violate the PB and PF footprints - although the degree to which even partial disruption of these footprints has on outcome remains unclear. To minimize damage to surrounding structures, including the PB and PF footprint, while allowing a screw length approximately two thirds of the metatarsal length, the CA screw position is recommended. This position balances the desire to maximize pull out strength while avoiding cortical penetration or inadvertent fracture site distraction.

Determinants of HbA1c reduction with FreeStyle Libre flash glucose monitoring (FLARE-NL 5).

AIMS: To identify factors predicting HbA1c reduction in patients with diabetes mellitus (DM) using FreeStyle Libre Flash Glucose Monitoring (FSL-FGM). METHODS: Data from a 12-month prospective nation-wide FSL registry were used and analysed with multivariable regression. For the present study we included patients with hypoglycaemia unawareness or unexpected hypoglycaemias (n = 566) and persons who did not reach acceptable glycaemic control (HbA1c > 70 mmol/mol (8.5%)) (n = 294). People with other indications for use, such as sensation loss of the fingers or individuals already using FSL-FGM or rtCGM, were excluded (37%). RESULTS: Eight hundred and sixty persons (55% male with a mean age of 46.7 (±16.4) years) were included. Baseline HbA1c was 65.1 (±14.5) mmol/mol (8.1 ± 1.3%), 75% of the patients had type 1 DM and 37% had microvascular complications. Data concerning HbA1c was present for 482 (56.0%) at 6 months and 423 (49.2%) persons at 12 months. A significant reduction in HbA1c (≥5 mmol/mol (0.5%)) was present in 187 (22%) persons. For these persons, median HbA1c reduction was -9.0 [-13.0, -4.0] mmol/mol (-0.82 [-1.19, -0.37]%) at 6 months and -9.0 [-15.0, -7.0] mmol/mol (-0.82 [-1.37, -0.64]%) at 12 months. In multivariable regression analysis with age, gender and SF-12 physical and mental component scores as covariates, only baseline HbA1c was significant: -0.319 (SE 0.025; p < 0.001; R2 = 0.240 for the model). In exploratory analysis among subgroups with different indications for FSL-FGM use (hypoglycaemia unawareness or persistently high HbA1c) and persons with a significant HbA1c decrease over the study period, baseline HbA1c remained the only significant predictor. CONCLUSIONS: Among the variables we analysed in the present study, only high HbA1c at baseline predicts significant HbA1c reduction during FSL-CGM use.

Modeling the characteristics of spontaneous otoacoustic emissions in lizards.

Lizard auditory papillae have proven to be an attractive object for modelling the production of spontaneous otoacoustic emissions (SOAE). Here we use an established model (Vilfan and Duke, 2008) and extend it by exploring the effect of varying the number of oscillating elements, the strength of the parameters that describe the coupling between oscillators, the strength of the oscillators, and additive noise. The most remarkable result is that the actual number of oscillating elements hardly influences the spectral pattern, explaining why spectra from very different papillar dimensions are similar. Furthermore, the spacing between spectral peaks primarily depends on the reactive coupling between the oscillator elements. This is consistent with observed differences between lizard species with respect to tectorial covering of hair cells and SOAE peak spacings. Thus, the model provides a basic understanding of the variation in SOAE properties across lizard species.

Use of FreeStyle Libre Flash Monitor Register in the Netherlands (FLARE-NL1): Patient Experiences, Satisfaction, and Cost Analysis.

In patients with diabetes mellitus (DM), adequate glucose control is of major importance. When treatment schemes become more complicated, proper self-management through intermittent self-measurement of blood glucose (SMBG), among others, becomes crucial in achieving this goal. In the last decade, continuous glucose monitoring (CGM) has been on the rise, providing not only intermittent information but also information on continuous glucose trends. The FreeStyle Libre (FSL) Flash CGM system is a CGM system mainly used for patients with DM and is designed based on the same techniques as early CGMs. Compared with earlier CGMs, the FSL is factory calibrated, has no automated readings or direct alarms, and is cheaper to use. Although less accurate compared with the gold standard for SMBG, users report high satisfaction because it is easy to use and can help users monitor glucose trends. The Flash Monitor Register in the Netherlands (FLARE-NL) study aims to assess the effects of FSL Flash CGM use in daily practice. The study has a before-after design, with each participant being his or her own control. Users will be followed for at least 1 year. The endpoints include changes in HbA1c, frequency and severity of hypoglycemias, and quality of life. In addition, the effects of its use on work absenteeism rate, diabetes-related hospital admission rate, and daily functioning (including sports performance) will be studied. Furthermore, cost-benefit analysis based on the combination of registered information within the health insurance data will be investigated. Ultimately, the data gathered in this study will help increase the knowledge and skills of the use of the Flash CGM in daily practice and assess the financial impact on the use of the Flash CGM within the Dutch healthcare system.

Models to predict positive and negative effects of cochlear implantation on tinnitus.

OBJECTIVES: The effect of cochlear implantation on tinnitus is heterogeneous: implantation does not always reduce tinnitus and may even worsen tinnitus. Therefore, it is important to know which factors influence the consequences of cochlear implantation for tinnitus. To date, no consensus has been reached regarding the factors that influence tinnitus. This study aimed to create prognostic models, using binary logistic regression analyses to predict positive or negative changes in tinnitus after cochlear implantation. METHODS: For this study we retrospectively sent two questionnaire packages to 117 cochlear implant patients. RESULTS: In the binary logistic regression analyses of the responses to the questionnaires, it was not possible to create a significant model to predict a positive effect of cochlear implantation on tinnitus. However, a negative effect of cochlear implantation on tinnitus was predictable, using a backward stepwise selection method in a model including the Abbreviated Profile of Hearing Aid Benefit (APHAB) and Tinnitus Handicap Questionnaire (THQ) (P < .001, Nagelkerke R2 = 0.529). CONCLUSIONS: Our results suggest that the lower the preoperative tinnitus handicap and the preoperative hearing handicap, the higher the chance that cochlear implantation will worsen tinnitus. More research needs to be done, preferable in a big prospective study, to make this model instrumental for clinical decision making and preoperative patient counselling. However, our results might suggest that preoperative THQ and APHAB screening could be meaningful. Especially in patients who are afraid to develop tinnitus or tinnitus worsening as complication of cochlear implantation. LEVEL OF EVIDENCE: 4.

Laser therapy for onychomycosis in patients with diabetes at risk for foot ulcers: a randomized, quadruple-blind, sham-controlled trial (LASER-1).

BACKGROUND: Patients with diabetes mellitus are at high risk for onychomycosis, which is related to the development of foot ulcers. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the treatment of onychomycosis with local laser therapy. METHODS: In a single-centre, randomized (1:1), quadruple-blind, sham-controlled trial, patients and microbiological confirmation with diabetes mellitus, at risk for developing diabetic foot ulcers (Sims classification score 1, 2) and a clinical suspicion on onychomycosis, were randomized to either four sessions neodymium-doped yttrium aluminium garnet (Nd-YAG) 1064 nm laser or sham treatment. The primary outcome was clinical and microbiological cure of onychomycosis after 1-year follow-up. RESULTS: From March 2015 to July 2016, 64 patients were randomized; 63 could be analysed. Trichophyton rubrum was the most detected pathogen. There was no difference in the primary outcome between laser and sham treatment. With the exception of a subungual haematoma in the fifth toenail occurring 2 weeks after laser treatment, the results suggested that treatment with Nd-YAG 1064 nm laser is safe. CONCLUSION: At this moment, there is no evidence of any effect of laser treatment for onychomycosis in patients with diabetes at increased risk for foot ulcers, at least not within 1 year after treatment.

Association Between Subjective Tinnitus and Cervical Spine or Temporomandibular Disorders: A Systematic Review.

Movements of the neck and jaw may modulate the loudness and pitch of tinnitus. The aim of the present study was to systematically analyze the strength of associations between subjective tinnitus, cervical spine disorders (CSD), and temporomandibular disorders (TMD). A systematic literature search of the Medline, Embase, and Pedro databases was carried out on articles published up to September 2017. This covered studies in which tinnitus and CSD or TMD were studied as a primary or a secondary outcome and in which outcomes were compared with a control group. Included articles were evaluated on nine methodological quality criteria. Associations between tinnitus and CSD or TMD were expressed as odds ratios. In total, 2,139 articles were identified, of which 24 studies met the inclusion criteria. Twice, two studies were based on the same data set; consequently, 22 studies were included in the meta-analysis. Methodological quality was generally limited by a lack of blinding, comparability of groups, and nonvalidated instruments for assessing CSD. Results indicated that patients with tinnitus more frequently reported CSD than subjects without tinnitus. The odds ratio was 2.6 (95% CI [1.1, 6.4]). For TMD, a bidirectional association with tinnitus was found; odds ratios ranged from 2.3 (95%CI [1.5, 3.6]) for arthrogenous TMD to 6.7 (95%CI [2.4, 18.8]) for unspecified TMD. Funnel plots suggested a publication bias. After adjusting for this, the odds ratios decreased, but associations persisted. There is weak evidence for an association between subjective tinnitus and CSD and a bidirectional association between tinnitus and TMD.

Healthcare reimbursement costs of children with type 1 diabetes in the Netherlands, a observational nationwide study (Young Dudes-4).

BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children. Studies on costs related to T1DM are scarce and focused primarily on the costs directly related to diabetes. We aimed to investigate both the overall healthcare costs and the more specific costs related to the management of diabetes. METHODS: This is a retrospective and observational, nationwide cohort study of all Dutch children (aged 0-18 years) with T1DM. Data were collected from the national registry for healthcare reimbursement, in which all Dutch insurance companies combine their reimbursement data. In the Netherlands for all Dutch citizens health care is covered by law and all children are treated by hospital-based paediatricians. RESULTS: We analysed 6710 children distributed over 81 hospitals: 475 children in 6 university hospitals and 6235 children in 75 general hospitals. Total reimbursement for all children with T1DM over the period 2009 to 2011 was € 167,494,732 corresponding to an annual mean of € 55,831,577 of total costs and € 8326 euros per child. When comparing small (between 26 and 54 patients), medium (57-84 patients) and large (88-248 patients) general hospitals, costs per patient were highest in the hospitals with the highest number of T1DM patients. The costs for devices, secondary care and pharmaceutics had most impact on total expenditures. Over the study period, there was a slight decrease in per person costs. CONCLUSION: The overall health expenditure of a child with T1DM is more than € 8000 per patient per annum. Given the move towards more device-intensive multidisciplinary care for these patients, the costs of treating T1DM in children are likely to increase further in the coming years.

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia.

The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.

Performance of the FreeStyle Libre Flash glucose monitoring system in patients with type 1 and 2 diabetes mellitus.

OBJECTIVE: To evaluate the performance of the FreeStyle Libre Flash continuous glucose monitoring (FSL-CGM) system against established central laboratory methods. RESEARCH DESIGN AND METHODS: 20 subjects (8 type 1 diabetes mellitus, 12 type 2 diabetes mellitus) were analyzed. FSL-CGM sensor measurements (inserted in arm and abdomen) were compared with capillary blood glucose results analyzed with StatStrip as semigold standard. The glucose response after a standardized oral glucose load was measured by FSL-CGM and capillary samples analyzed by perchloric acid hexokinase (PCA-HK) method, StatStrip and FSL test strip (FSLC), and a commonly used CGM system (iPro2). RESULTS: FSL-CGM arm sensor readings showed 85.5% of paired readings falling within Clarke Error Grid (ISO 15197:2013) zone A when compared with StatStrip. For FSL-CGM abdomen and FSLC, these percentages were 64% and 98%, respectively. The overall correlation of FSL-CGM in the arm and the StatStrip indicates a performance with lower results with the FSL-CGM in the arm than expected based on the StatStrip in the lower glucose ranges, and higher results than expected in the higher ranges. Following a standardized glucose load, a slower rise in glucose level was observed for FSL-CGM arm as compared with PCA-HK, StatStrip, FSLC, and iPro2 during the first 45-60 min after glucose load ingestion. CONCLUSIONS: Certain matters need attention while using the FSL-CGM in daily life including the observed lower values in the lower ranges, and the underestimation of the effect of a meal on glucose response. These effects of such deviations can partly be overcome by optimizing the available user instructions. TRIAL REGISTRATION NUMBER: TC5348; results.

Irradiance levels of phototherapy devices: a national study in Dutch neonatal intensive care units.

OBJECTIVE: The objective of this study is to determine whether irradiance levels of phototherapy (PT) devices in Dutch neonatal intensive care units (NICUs) increased between 2008 and 2013. STUDY DESIGN: Irradiance of all types of PT devices, used in combination with incubators, was measured with a Dale 40 Radiometer (Fluke Biomedical, Everett, WA, USA) in all 10 Dutch NICUs. RESULTS: Irradiance increased in seven NICUs. Median (range) irradiance increased from 9.7 (4.3-32.6) to 16.4 (6.8-41) µW cm-2 nm-1 for 24 overhead devices (P=0.004) and from 6.8 (0.8-15.6) to 22.3 (1.1-36.3) µW cm-2 nm-1 for 12 underneath devices (P=0.014). Five light-emitting diode (LED)-based devices were used in 2013 and one in 2008. The mean distance between overhead PT device and infant decreased by ~9 cm (P<0.001). Significantly more devices delivered minimal (10 µW cm-2 nm-1) recommended irradiance levels (80 vs ~45%; P=0.002). CONCLUSION: Irradiance of PT devices still varies, but has markedly improved since 2008 due to shorter distances between PT device and infant, and introduction of better performing LED-based devices.

Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus.

AIMS: Elevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients. METHODS: Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-ß-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed. RESULTS: Estimated mean change in SHBG was -10.3nmol/L (95% CI: -17.4, -3.2) during CIPII and 3.7nmol/L (95% CI: -12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was -6.6nmol/L (95% CI: -17.5, 4.3); -12.7nmol/L (95% CI: -25.1, -0.4) for males and -1.7nmol/L (95% CI: -24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; -15.8nmol/L (95% CI: -24.2, -7.5) and -8.3nmol/L (95% CI: -14.4, -2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males. CONCLUSIONS: SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

Intraperitoneal versus subcutaneous insulin therapy in the treatment of type 1 diabetes mellitus.

BACKGROUND: Continuous intraperitoneal insulin infusion (CIPII), a last-resort type 1 diabetes mellitus (T1DM) treatment, has only been investigated in small or controlled studies. We aimed to investigate glycaemia and quality of life (QoL) with CIPII versus subcutaneous (SC) insulin therapy during usual T1DM care. METHODS: A prospective, observational case-control study. CIPII-treated cases were matched to SC controls. The primary endpoint was a non-inferiority assessment (pre-defined margin of -5.5 mmol÷mol) of the baseline adjusted difference in HbA1c between groups during a 26-week follow-up. Secondary outcomes included QoL, clinical and biochemical measurements. RESULTS: In total, 183 patients were analysed (CIPII n = 39 and SC n = 144). The HbA1c difference between treatment groups was -3.0 mmol÷mol (95% CI -5.0, -1.0), being lower in the SC group. Patients using SC insulin therapy spent less percentage of time in hyperglycaemia (-9.3% (95% CI -15.8, -2.8)) and more in euglycaemia (6.9% (95% CI 1.2, 12.5) as compared with CIPII-treated patients. Besides a 3.6 U÷l (95% CI 1.2, 6.0) lower concentration of alanine aminotransferase with CIPII, no biochemical and clinical differences were present. Most QoL scores were lower at baseline among CIPII-treated patients. However, besides lower health status, there were no differences in the baseline-adjusted general and diabetes-specific QoL and treatment satisfaction. CONCLUSION: Although patients using CIPII had a higher glycaemic profile compared with patients using SC insulin therapy, the HbA1c difference was non-inferior. Overall, health status was lower among CIPII-treated patients, although diabetes-specific QoL and treatment satisfaction was similar to subcutaneously treated patients.