European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates of ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact fibroblast growth factor 23 and uncarboxylated-unphosphorylated matrix-Gla protein-a cooperation between the EFLM Working Group on Biological Variation and the International Osteoporosis Foundation-International Federation of Clinical Chemistry Committee on Bone Metabolism.

We have calculated the biological variation (BV) of different bone metabolism biomarkers on a large, well-described cohort of subjects. BV is important to calculate reference change value (or least significant change) which allows evaluating if the difference observed between two consecutive measurements in a patient is biologically significant or not. INTRODUCTION: Within-subject (CVI) and between-subject (CVG) biological variation (BV) estimates are essential in determining both analytical performance specifications (APS) and reference change values (RCV). Previously published estimates of BV for bone metabolism biomarkers are generally not compliant with the most up-to-date quality criteria for BV studies. We calculated the BV and RCV for different bone metabolism markers, namely ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin (OC), intact fibroblast growth factor 23 (iFGF-23), and uncarboxylated-unphosphorylated Matrix-Gla Protein (uCuP-MGP) using samples from the European Biological Variation Study (EuBIVAS). METHODS: In the EuBIVAS, 91 subjects were recruited from six European laboratories. Fasting blood samples were obtained weekly for ten consecutive weeks. The samples were run in duplicate on IDS iSYS or DiaSorin Liaison instruments. The results were subjected to outlier and variance homogeneity analysis before CV-ANOVA was used to obtain the BV estimates. RESULTS: We found no effect of gender upon the CVI estimates. The following CVI estimates with 95% confidence intervals (95% CI) were obtained: ß-CTX 15.1% (14.4-16.0%), PINP 8.8% (8.4-9.3%), OC 8.9% (8.5-9.4%), iFGF23 13.9% (13.2-14.7%), and uCuP-MGP 6.9% (6.1-7.3%). CONCLUSIONS: The EuBIVAS has provided updated BV estimates for bone markers, including iFGF23, which have not been previously published, facilitating the improved follow-up of patients being treated for metabolic bone disease.

Experimental study showed that adding fortifier and extra-hydrolysed proteins to preterm infant mothers' milk increased osmolality.

AIM: Measuring milk osmolality after adjustable fortification is clinically relevant, as values exceeding recommended safety thresholds might result in gastrointestinal consequences. The aim of this study was to evaluate the effect of four fortification levels and storage time on the osmolality of human milk. METHODS: This was an experimental study using 71 spare samples of fresh breastmilk collected from 31 mothers of preterm infants. Osmolality was measured before and after adding commercial human milk fortifier containing dextrinomaltose and hydrolysed proteins at four different concentrations. Measurements were performed at various points during the 23 hours after fortification. RESULTS: The mean basal osmolality of the 71 human milk samples was 296 ± 14 milliosmoles (mOsm)/kg, and these remained stable over a period of 23 hours. Just after fortification, the four fortified formulas showed higher osmolalities than the nonfortified human milk, ranging between 384 ± 14 and 486 ± 15 mOsm/kg, respectively (p < 0.01). This osmolality increased significantly from 20 minutes to 23 hours after fortification (p < 0.05). CONCLUSION: Adding fortifier and extra-hydrolysed proteins to human preterm milk increased osmolality, and these osmolality levels also increased with time. We recommend evaluating the risk of hyperosmolality when a higher fortification level is needed, to avoid gastrointestinal problems.

Interobserver reliability of store-and-forward teledermatology in a clinical practice setting.

INTRODUCTION AND OBJECTIVES: Although many studies have evaluated the diagnostic reliability of store-and-forward (SF) teledermatology, the reliability of the technique for the diagnosis of general skin conditions in a clinical practice setting has never been demonstrated. We evaluated the reliability of SF teledermatology in clinical practice by analyzing the diagnostic agreement achieved in a subgroup of patients from the DERMATEL-2 study. MATERIAL AND METHODS: Patients referred from primary care settings were randomized to 3 groups: SF, a combination of videoconferencing and SF technology (VC-SF), and a control group. This article focuses on the SF group. Clinical data were recorded and photographs taken by primary care physicians, who forwarded the data electronically. Each SF consultation package was assessed by 3 dermatologists (D1,D2,D3). Subsequently all the patients were assessed by a single dermatologist (D1) in a face-to-face consultation. Finally, 2 other dermatologists (D4,D5) assessed the agreement between the diagnoses obtained by SF and FF. RESULTS: In total, 457 patients (200 males and 257 females) aged between 2 months and 86 years were randomized (192 to SF, 176 to VC-SF, and 89 to the control group). The diagnostic categories were as follows: tumors (49.4%), inflammatory (25.7%), adnexal (11%), infectious (9.4%) and other processes (4.4%) Since 170 patients had consultations deemed valid for analysis, the study included a total of 510 SF assessments. Most of the images and clinical records were of high quality (71.2% and 91.2% respectively), and diagnostic confidence was high in 81.4% of the cases studied. In 58.4% of cases the condition was managed exclusively by teledermatology. Levels of complete and aggregate interobserver agreement between SF and face-to-face evaluators were 0,72 and 0.90, respectively, for diagnosis and 0.61 and 0.80 for treatment. Diagnostic agreement correlated with the image quality (P < .001), diagnostic confidence (P<.001), felt need for conventional consultation (P<.001), and the quality of the clinical record (P=.013). CONCLUSION: The interobserver reliability of SF diagnosis in clinical practice is good. Dermatologists are able to predict errors in diagnosis by analyzing their own diagnostic confidence and evaluating the quality of the images.

Robot-assisted partial nephrectomy using the novel Hugo™ RAS system: Feasibility, setting and perioperative outcomes of the first off-clamp series.

INTRODUCTION: Hugo Robot-Assisted Surgery (RAS) System has been conceived with enhanced modularity but its role for nephron-sparing surgery setting still remains poorly explored. We aimed to describe our experience in robot-assisted partial nephrectomy (RAPN) with a three-arms setting for the first off-clamp series using the new Hugo RAS System. METHODS: Patients were placed on an extended flank position at the margin of the surgical bed with a slightly flexion (45°). The first 11 mm robotic trocar (camera port) was placed along the pararectal line 14 ± 2 cm far from the umbilicus. The pneumoperitoneum was then induced through the AirSeal system (SurgiQuest, Milford, Connecticut, USA©). Two more 8 mm operative robotic ports were placed under direct vision, either 8 ± 1 cm far from optic's port. Two 12 mm laparoscopic ports for bed-assistant were placed between robotic ports. Monopolar curved shears, fenestrated grasper, and large needle driver were used in a three-instruments configuration. RESULTS: Off-clamp RAPN was successfully performed in seven patients with cT1 renal masses using a trans-peritoneal route. Median port placement and docking time was 6 min (IQR, 4-8 min). Hemostasis was achieved through renorraphy using a single transfix stitch with sliding clips technique. There was no need for additional ports placement. No intraoperative complications occurred, no clashing of robotic instruments or between the robotic arms was observed. No technical failures of the system occurred. Median console time was 83 min (IQR, 68-115 min). Median estimated blood loss were 200 ml (IQR, 50-400 ml). All patients were discharged between post-operative day 2 and 3, without the need of hospital readmission. No complications were recorded within the first 30 post-operative days. CONCLUSIONS: We performed the first series of off-clamp RAPN using the novel HUGO RAS System. This novel robotic platform showed an easy-friendly docking system, providing excellent perioperative outcomes with a simple three-arms configuration.

AMI in (bi)ventricular pacing - do not discard the ECG.

BACKGROUND: There is a growing number of patients with ventricular paced rhythm, who present to the emergency department with chest pain. The diagnosis of ST-segment elevation myocardial infarction (STEMI) and subsequent percutaneous coronary intervention (PCI) is often postponed, as the 12 leads-electrocardiogram (ECG) is discarded as not interpretable. There is a growing body of literature that suggests that Smith-modified Sgarbossa criteria can be applied for the diagnosis of STEMI in patients with paced rhythms. These criteria were originally developed for the interpretation of ECGs in patients with a left bundle branch block (LBBB) and chest pain, but have been expanded to paced ECGs. METHODOLOGY: We present three case reports with chest pain and right ventricular or biventricular pacing. FINDINGS: In all three cases, the Smith-modified Sgarbossa was positive and the diagnosis of STEMI could have been made early on. IMPLICATIONS: It remains important to look for ST-segment deviations and to compare the symptomatic ECG with previous asymptomatic ECGs. As the number of patients with potential acute myocardial infarction (AMI) and paced rhythms is likely to rise in the future, these criteria should be known to emergency physicians and cardiologists.

Wolff Parkinson White and recreational (meth)amphetamine use: a potentially lethal combination.

Cardiac arrest in Wolff-Parkinson-White (WPW) is a rare event, and although some patients appear to be at greater risk, there is no consensus on clear risk factors. We present a case of a 23-year-old male patient, with a known history of WPW pattern, who suffered an out of hospital ventricular fibrillation after the consumption of rather small dose of (meth)amphetamines. The use of illegal drug can predispose WPW patients to fatal arrhythmia and cardiac arrest. Patients with WPW pattern should be well informed about the risks of (meth)amphetamines and some might be considered for medical therapy or catheter ablation.

Systematic review of the biological variation data for diabetes related analytes.

BACKGROUND: Objective interpretation of laboratory test results used to diagnose and monitor diabetes mellitus in part requires the application of biological variation data (BVD). The quality of published BVD has been questioned. The aim of this study was to quality assess publications reporting BVD for diabetes-related analytes using the Biological Variation Data Critical Appraisal Checklist (BIVAC); to assess whether published BVD are fit for purpose and whether the study design and population attributes influence BVD estimates and to undertake a meta-analysis of the BVD from BIVAC-assessed publications. METHODS: Publications reporting data for glucose, HbA1c, adiponectin, C-peptide, fructosamine, insulin like growth factor 1 (IGF-1), insulin like growth factor binding protein 3 (IGFBP-3), insulin, lactate and pyruvate were identified using a systematic literature search. These publications were assessed using the BIVAC, receiving grades A, B, C or D, where A is of highest quality. A meta-analysis of the BVD from the assessed studies utilised weightings based upon BIVAC grades and the width of the data confidence intervals to generate global BVD estimates. RESULTS: BIVAC assessment of 47 publications delivered 1 A, 3 B, 39C and 4 D gradings. Publications relating to adiponectin, C-peptide, IGF-1, IGFBP-3, lactate and pyruvate were all assessed as grade C. Meta-analysis enabled global BV estimates for all analytes except pyruvate, lactate and fructosamine. CONCLUSIONS: This study delivers updated and evidence-based BV estimates for diabetes-related analytes. There remains a need for delivery of new high-quality BV studies for several clinically important analytes.

Determinants of the quality of basic life support by hospital nurses.

INTRODUCTION: Good quality basic life support (BLS) results in better survival. BLS is a core competence of nurses but despite regular refresher training, the quality of BLS is often poor and the reasons for this are not well known. We therefore investigated the relation between BLS quality and some of its potential determinants. MATERIALS AND METHODS: During a BLS refresher course, 296 nurses from non-critical care wards completed a questionnaire including demographic data and a "self-confidence" score. Subsequently, they performed a BLS test on a manikin connected to a PC using Skillreporting System software (Laerdal, Norway). The following variables were recorded: number of ventilations/min, tidal volume, number of compressions/min, compression rate, compression depth, "good ventilation" (n >or=4 min(-1) and tidal volume=700-1000 ml) and "good compression" (n >or=40 min(-1) and rate=80-120 min(-1) and compression depth=40-50mm). To detect independent determinants of BLS quality, associations between the demographic data and the objective variables of BLS quality were examined. RESULTS: Forty-three percent of the nurses rated their confidence as good or very good. Male gender was associated with good compression (P<0.001). Greater self-confidence was also associated with good ventilation (P<0.03) and with good compression (P<0.001). A short time since last BLS training was associated with a higher number of ventilations/min (P=0.01). A short time since last experience of CPR was associated with a higher number of compressions (P<0.01). CONCLUSIONS: Male gender, greater self-confidence, recent BLS training and recent CPR were associated with better quality of BLS.

Correlation of preoperative findings in computed axial tomography with the presence of difficult airway in patients undergoing head and neck otorhinolaryngological surgery. / Correlación de hallazgos preoperatorios en la tomografía axial computarizada con la presencia de vía aérea difícil en pacientes intervenidos mediante cirugía otorrinolaringológica de cabeza y cuello.

OBJECTIVES: To establish a correlation between 4 measurements made on preoperative computed axial tomography and the presence of difficult airway, as well as its clinical prediction in patients undergoing otorhinolaryngological surgery. MATERIAL AND METHODS: A retrospective, observational study was carried out using the information gathered from the clinical notes of 104 patients undergoing general anaesthesia and endotracheal intubation for oncological otorhinolaryngological surgery over a period of 36 months. Based on the findings in the preoperative imaging tests, a multivariate logistic regression analysis was performed, where the dependent variable was the presence of extreme grades of visualization of the glottis visualisation (Cormack III-IV) or the presence of predictors of difficult intubation (Mallampati III-IV). This resulted in a total of 4 tomographic and clinical factors of difficult airway being introduced in this model. RESULTS: In the Cormack III-IV group, the results were not statistically significant in the multivariate model when compared to the tomography predictors, distance from epiglottis to posterior pharyngeal wall (95% CI; 0.030 - 2.31, P<.05), and the distance from the base of the tongue to the posterior pharyngeal wall (95% CI; 0.018-1.37, P<.05). In the Mallampati III-IV group, in the multivariate model only the distance from the vocal cords to the posterior pharyngeal wall showed clinically significant results (95% CI; 0.104 - 8.53, P<.05). CONCLUSIONS: In the approach to the airway, reliance on predictors is based on physical examination to anticipate situations that put oxygenation and ventilation of the patients at risk. There are still insufficient data to recommend imaging tests in this area, however it seems that in the future they may be added to the diagnostic performance of physical examination as predictors of difficult airway.

Out-of-hospital ventricular fibrillation in patients with acute myocardial infarction: coronary angiographic determinants.

OBJECTIVES: The study intended to compare the acute coronary anatomy of patients with acute myocardial infarction (AMI) complicated by out-of-hospital ventricular fibrillation (VF) versus patients with AMI without this complication. BACKGROUND: More than half of the deaths associated with AMI occur out of the hospital and within 1 h of symptom onset. The angiographic determinants of out-of-hospital VF in patients with AMI have not been investigated in detail. METHODS: Acute coronary angiographic findings of 72 consecutive patients with AMI complicated by out-of-hospital VF were compared with findings from 144 matched patients with AMI without this complication. RESULTS: Patients with an acute occlusion of the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) had a higher risk for out-of-hospital VF compared with patients with an acute occlusion of the right coronary artery (RCA) (odds ratio and 95% confidence interval, respectively, 4.82 [2.35 to 9.92] and 4.92 [2.34 to 10.39]). With regard to extent of coronary artery disease (CAD), the location of the culprit lesion in the coronary arteries (proximal vs. mid or distal), the flow in the infarct related artery (IRA), the presence or absence of collaterals to the IRA and chronic occlusions, there were no differences between the two groups. CONCLUSIONS: Acute myocardial infarction due to occlusion in the left coronary artery (LCA) is associated with greater risk for out-of-hospital VF compared to the RCA. The location of occlusion within LCA (LAD, LCx, proximal or distal), amount of myocardium at risk for necrosis and extent of CAD are not related to out-of-hospital VF.

[Effect of hygiene interventions on the thermal stability of extremely low-birth-weight newborns in the first two weeks of life]. / Repercusión del aseo en la estabilidad térmica del recién nacido de extremado bajo peso durante las primeras dos semanas de vida.

INTRODUCTION: A prospective study was performed of a cohort of extremely low-birth-weight (ELBW) premature neonates (birth weight 500 to 1,000 g) consecutively admitted to the neonatal intensive care unit. The aim of this study was to examine the thermal changes that occur during all the hygiene-related interventions in ELBW infants in the first 2 weeks of life. PATIENTS AND METHODS: The study was carried out for 10 consecutive months in the Neonatology Service of La Paz University Hospital. We studied all consecutively admitted ELBW infants who satisfied the following criteria: a) adequate weight for gestational age; b) survival for at least 1 week, and c) no major congenital malformations or dysmorphic features. The infants included in the study were managed according to a standard care protocol for maintaining thermal stability and preventing cold-induced stress. Central temperature (Tc) was measured in the axilla and peripheral temperature (Tp) was measured on the sole of the foot. Both temperatures were continuously monitored for a) a period of scheduled non-handling--baseline period--and b) during and after a series of "hygiene interventions". In each of these periods, Tc and Tp were continuously monitored and recorded at 10 min intervals for the first 30 minutes and then at 30 min intervals until completing a 180 min period. RESULTS: Although incubator temperature was raised by a mean of 3 degrees C during hygiene interventions, hygiene was accompanied by a change in body temperature that remained fairly constant throughout the study period; Tc and Tp decreased by a mean of 1 degrees C with respect to baseline temperature. A fall in axillary temperature to less than 36.5 degrees C was observed in 87.4 % of recordings and a fall to less than 36 degrees C was observed in 45.5 %; axillary temperature remained below 36.5 degrees C for a mean duration of almost 1 hour. The differential temperature (Td 5 Tc - Tp), an indicator of thermal stress, was more than 1 degrees C for a mean duration of more than 80 min and > 2 degrees C for more than 20 minutes in both the first and second weeks of life. CONCLUSIONS: During hygiene interventions, ELBW infants experienced a sharp fall in central and peripheral body temperature. After hygiene interventions, these neonates had a Td suggestive of prolonged thermal stress, despite the use of standardized care protocols designed to avoid or minimize the potential effects of hygiene interventions on neonatal temperature.