Decision aids for people with Type 2 diabetes mellitus: an effectiveness rapid review and meta-analysis.

AIMS: To perform a rapid review and meta-analysis of randomized controlled trials (RCTs) evaluating patient decision aids (PtDAs) for people with Type 2 diabetes mellitus. METHODS: We searched Medline and the Cochrane Library for RCTs assessing PtDAs in people with Type 2 diabetes. PtDAs were defined as tools designed to help people engage in decision-making about healthcare options, such as making treatment choices or setting therapeutic goals. The study selection process was facilitated by an automated screening tool to identify RCTs. We classified outcomes into seven domains and conducted meta-analyses using random effects models. RESULTS: We included a total of 15 studies, nine of which were cluster RCTs, that evaluated 10 PtDAs. Thirteen trials compared a PtDA with usual care or usual care plus educational material, whereas two RCTs compared individually tailored vs. non-tailored PtDAs. Meta-analyses showed a favourable effect of PtDAs compared with usual care in reducing decisional conflict [weighted mean difference (WMD) -4.66, 95% confidence interval (CI) -7.93 to -1.39] and in improving knowledge (WMD 20.46, 95% CI 9.13 to 3.77). Use of PtDAs resulted in more active involvement in decision-making during the consultation, although no effect was evident in terms of glycaemic control or self-reported medication adherence. CONCLUSIONS: PtDAs for people with Type 2 diabetes can improve the quality of decision-making and increase knowledge transfer. Interpretation of our findings is attenuated due to limitations related to the rapid review approach, including searching only two databases and performing data extraction and risk of bias assessment by a single reviewer.

Preparation of pharmaceutical cocrystal formulations via melt mixing technique: A thermodynamic perspective.

The aim of the present study was to evaluate the thermodynamic properties of in-situ formation of cocrystal formulations by the melt-mixing method. Specifically, the thermodynamic mixing behaviour of carbamazepine-nicotinamide and ibuprofen-nicotinamide cocrystals prepared with the aid of Soluplus® (SOL) were evaluated using thermodynamic lattice-based solution theories. Thermodynamic miscibility of both cocrystals with SOL was predicted by calculating Gibb's free energy based on the Flory-Huggins (FH) interaction parameter (χ), while the activity coefficient of cocrystals estimated with the aid of solid-liquid equilibrium equation and FH lattice theory, showed good thermodynamic miscibility of the components at elevated temperatures used normally during melt-mixing based processes. Complete phase transition diagrams constructed with the aid of DSC measurements and FH solution theory, suggested the existence of two transition zones: (1) a stable cocrystal zone, located at the right-hand-side of the spinodal phase separation curve, where stable cocrystals are prepared and (2) an unstable cocrystal zone, located at the left-hand-side of the spinodal curve up to liquidus, where the matrixforming polymer sets a kinetic barrier to recrystallization and hence, a barrier to the formation of cocrystals. The validity of the suggested thermodynamic phase transition zones was experimentally verified by ATR-FTIR and hot-stage polarized light microscopy.

Artificial neural networks (ANNs) and partial least squares (PLS) regression in the quantitative analysis of cocrystal formulations by Raman and ATR-FTIR spectroscopy.

The present work describes the development of an efficient, fast and accurate method for the quantification of polymer-based cocrystal formulations. Specifically, the content of carbamazepine-nicotinamide (CBZ/NIC) and ibuprofen-nicotinamide (IBU/NIC) cocrystals in Soluplus®-based formulations was independently determined with the aid of either Raman or Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR) spectroscopy. Spectra peaks from mixtures of IBU/NIC and CBZ/NIC cocrystals with Soluplus at a ratio ranging from 90/10 to 1/99 w/w (cocrystal to SOL) were evaluated and modelled with the aid of feed-forward, back-propagation artificial neural networks (ANNs) and partial least squares (PLS) regression analysis. A 25 full-factorial experimental design was employed in order to evaluate the effect of ANN's structure (number of hidden units) and training (number of iteration cycles) parameters along with the effect of Raman or FTIR spectra region and data preprocessing (direct orthogonal signal correction - DOSC, second derivative, or no preprocessing) on ANN's fitting performance. Results showed that when DOSC preprocessing was employed excellent ANN fitting in both Raman (root mean squared error of prediction (RMSEp) values of 0.43 and 0.34 for IBU/NIC-SOL and CBZ/NIC-SOL, respectively) and FTIR (RMSEp values of 0.04 and 0.03 for IBU/NIC-SOL and CBZ/NIC-SOL, respectively) spectra was obtained. Comparison of ANNs fitting results with PLS regression (RMSEp for IBU/NIC-SOL was 0.94 and 7.36, and for CBZ/NIC-SOL 7.29 and 15.63, using Raman and FTIR analysis, respectively) revealed ANN's fitting superiority, which can be attributed to their inherent non-linear predictive ability.

Comparative transcriptome analysis of equine alveolar macrophages.

REASONS FOR PERFORMING STUDY: Alveolar macrophages (AMs) are the first line of defence against pathogens in the lungs of all mammalian species and thus may constitute appropriate therapeutic target cells in the treatment and prevention of opportunistic airway infections. Therefore, acquiring a better understanding of equine macrophage biology is of paramount importance in addressing this issue in relation to the horse. OBJECTIVES: To compare the transcriptome of equine AMs with that of equine peritoneal macrophages (PMs) and to investigate the effect of lipopolysaccharide (LPS) on equine AM. STUDY DESIGN: Gene expression study of equine AMs. METHODS: Cells from both bronchoalveolar and peritoneal lavage fluid were isolated from systemically healthy horses that had been submitted to euthanasia. Cells were cryopreserved. RNA was extracted and comparative microarray analyses were performed in AMs and PMs, and in AMs treated and untreated with LPS. Comparisons with published data derived from human AM studies were made, with particular focus on LPS-induced inflammatory status. RESULTS: The comparison between AMs and PMs revealed the differential basal expression of 451 genes. Gene expression analysis revealed an alternative (M2) macrophage polarisation profile in AMs and a hybrid macrophage activation profile in PMs, a phenomenon potentially attributable to a degree of induced endotoxin tolerance. The gene expression profile of equine AMs following LPS stimulation revealed significant changes in the expression of 240 genes, including well-known upregulated inflammatory genes. This LPS-induced gene expression profile of equine AMs more closely resembles that of human rather than murine macrophages. CONCLUSIONS: This study improves current understanding of equine macrophage biology. These data suggest that the horse may represent a suitable animal model for the study of human macrophage-associated lung inflammation and data derived from human macrophage studies may have significant relevance to the horse.

Hemodynamics after endoscopic submucosal injection of epinephrine in a porcine model.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal injection of epinephrine may cause systemic effects on the cardiovascular system. The aim of this experimental study was to assess systemic hemodynamic changes after submucosal injection of epinephrine during upper gastrointestinal endoscopy in a porcine model. METHODS: Measurements were taken from 12 pigs under general anesthesia. During gastroscopy 5 mL of normal saline, and 2.5 mL and 5 mL of epinephrine (1:10,000) were injected into the submucosal layers of the gastric antrum, corpus, and distal esophagus. After each injection, the cardiac index and global end diastolic volume index (GEDVI, reflecting preload) were measured every 3 minutes by transpulmonary thermodilution for a minimum of 12 minutes. The following parameters were also recorded: heart rate, mean arterial pressure (MAP), and systemic vascular resistance index (SVRI, reflecting afterload). RESULTS: Significant hemodynamic changes were observed after submucosal injection of epinephrine into the esophagus, including heart rate (maximum + 4 %) and MAP (maximum - 4%) after injection of 2.5 mL epinephrine, and stronger changes in heart rate (maximum +13%), cardiac index (maximum +21%), MAP (maximum -4%), and SVRI (maximum -12%) after the injection of 5 mL epinephrine. After submucosal injection of epinephrine into the gastric antrum and corpus, hemodynamic effects were less evident. Here significant changes were observed in heart rate (maximum +3%), MAP (maximum -2%), cardiac index (maximum +7%), and SVRI (maximum -8%) only after the injection of 5 mL epinephrine into the antrum. CONCLUSION: Endoscopic submucosal injection of epinephrine is associated with changes in systemic hemodynamic parameters, especially when performed in the esophagus, and the procedure might therefore induce harmful side effects.

A novel and practicable ERCP training system with simulated fluoroscopy.

INTRODUCTION: Simulators facilitate the acquisition of technical skills for endoscopy. Here, we describe the development, introduction, and first evaluation of a novel generation of mechanical endoscopic retrograde cholangiopancreatography (ERCP) simulation models with simulated fluoroscopy, the X-Vision ERCP Training System. METHODS: A custom-made modular ERCP simulation system was built with the use of universally obtainable materials and tools. The trainee controls ERCP activities on two screens: the aspect of the papilla and duodenum is shown on the conventional endoscopy monitor, and the trainee's actions in the equivalents of the pancreaticobiliary ducts are shown on the viewing screen of the model. Thereby, the latter screen serves as a substitute for fluoroscopy. Currently, four different models are available, allowing simulation of selective cannulation of the pancreatic or bile duct, intubation of differently arranged papillae, stent placement, and sphincterotomy of a biopapilla. The X-Vision ERCP Training System was first used during an ERCP course attended by 26 endoscopists. Trainees were supervised by an ERCP expert and an experienced ERCP nurse at each training model. The training system was evaluated by the participants and experts using a specific questionnaire. RESULTS: During the course there were no technical problems related to the X-Vision ERCP Training System. After sphincterotomy the organic papillae could easily be exchanged within less than 15 seconds. Overall, the X-Vision ERCP Training System achieved favorable results in all categories assessed. CONCLUSION: The new X-Vision ERCP Training System is simple and effective. A first evaluation in the context of an ERCP course showed impressive results.

Changes in intra-abdominal pressure, hemodynamics, and peak inspiratory pressure during gastroscopy in a porcine model.

BACKGROUND AND STUDY AIMS: The aim of this experimental study was to assess the effect of gastric insufflation on intra-abdominal pressure (IAP) and associated hemodynamic and respiratory changes during upper gastrointestinal endoscopy. METHODS: Measurements were taken from pigs under general anesthesia with controlled ventilation. Gastroscopy was carried out with continuous insufflation of air by a standard endoscopic light source/insufflator. The cardiac index and global end-diastolic volume index (GEDVI; reflecting preload) were measured by transpulmonary thermodilution. IAP, heart rate, mean arterial pressure (MAP), central venous pressure, systemic vascular resistance index (SVRI; reflecting afterload), peak inspiratory pressure (PIP), and oxygenation (SaO (2)) were also recorded. RESULTS: A total of 266 paired measurements (at the time of transpulmonary thermodilution) were taken from 14 animals. During air insufflation, we observed a significant rise in IAP in all animals up to intermittent values of 22 mm Hg. IAP and PIP correlated well (r = 0.666, P < 0.001), with the latter reaching values as high as 45 mbar in one pig, leading to respiratory compromise. Only marginal changes in heart rate, and a continuous, almost significant rise in MAP (due to a significant increase in SVRI) were recorded. We observed a slight increase in GEDVI, predominantly during the initial phase of air insufflation. The cardiac index showed no substantial changes. There were no episodes of hemodynamic instability, nor a decline in SaO (2). CONCLUSIONS: Air insufflation during gastroscopy resulted in a significant increase in IAP. The main clinically relevant finding was a steady increase in SVRI. Major increments in PIP suggest a role of intra-abdominal hypertension in otherwise unexplained respiratory compromise during upper gastrointestinal endoscopy.

Effect of pneumoperitoneum on hemodynamics and inspiratory pressures during natural orifice transluminal endoscopic surgery (NOTES): an experimental, controlled study in an acute porcine model.

BACKGROUND AND STUDY AIM: Physiologic reactions during natural orifice transluminal endoscopic surgery (NOTES) may differ from those at laparoscopy. This experimental study assessed the effect of pneumoperitoneum induced by endoscope air pump on hemodynamics and inspiratory pressures during transgastric peritoneoscopy. METHODS: Transgastric peritoneoscopy was performed in 11 female pigs (35 - 50 kg) under general anesthesia. Five pigs with controlled insufflation and no endoscopic intervention served as controls. Cardiac index and global end-diastolic volume index (GEDVI; reflecting preload) were measured every 3 minutes by transpulmonary thermodilution. We also recorded: intra-abdominal pressure (IAP), heart rate, mean arterial pressure (MAP), systemic vascular resistance index (SVRI; reflecting afterload), peak inspiratory pressure (PIP), and oxygenation. RESULTS: One study group pig was excluded from analysis because of a major complication related to the gastric incision. In the remaining 15 animals we performed 264 paired measurements. On-demand insufflation in the study group produced wide variation in intra-abdominal pressures; the control group demonstrated minimal fluctuation around a predetermined value. In the study group, IAP and PIP correlated well ( R = 0.667, P = 0.000), with maximum PIP values of 40 mbar contrasting with the control group maximum of 26.5 mbar. Hemodynamically, there was a minor decrease of cardiac index in the study group (in contrast to the control group). Relative changes in cardiac index and IAP during transgastric peritoneoscopy correlated highly significantly ( R = - 0.416, P = 0.000). Neither group showed hemodynamic instability or decline in oxygen saturation. CONCLUSIONS: On-demand insufflation with a standard endoscopic light source/insufflator resulted in a marked median increase and wide variation in IAP throughout transgastric peritoneoscopy. Hemodynamic changes were moderate. However, major increases in PIP suggest a need for stricter control of intra-abdominal hypertension during NOTES.

Transgastric in vivo histology in the peritoneal cavity using miniprobe-based confocal fluorescence microscopy in an acute porcine model.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) is an emerging technology. Apart from its therapeutic implications, this type of access to the peritoneal cavity might also be useful for targeted in vivo histological investigation by means of confocal fluorescence microscopy. In this study we therefore aimed to assess the feasibility of miniprobe-based confocal fluorescence microscopy during transgastric endoscopy in an acute porcine model. MATERIALS AND METHODS: Transgastric in vivo histology was performed in five pigs, under general anesthesia. After incision of the anterior gastric wall, a double-channel video gastroscope was advanced into the peritoneal cavity. A flexible confocal miniprobe was introduced through the instrument channel of the endoscope after intravenous injection of 10 mL of fluorescein 1% in four of the pigs and of 50 mL of fluorescein isothiocyanate-dextran 150 000 4% in the fifth pig. The tip of the miniprobe was then placed on the peritoneal layer, the liver, and the spleen for confocal laser microscopy. RESULTS: Probes were easily attached to the peritoneal layer, the liver, and the spleen under direct visualization with the endoscope. Dynamic microscopic images of these organs were obtained with a frame rate of 12 frames per second. The flow of erythrocytes through blood vessels could be seen. The microstructural components of organs, such as lobules of the liver, were also easily identified. CONCLUSIONS: In vivo histology in the peritoneal cavity is feasible during NOTES and this technique combines the minimally invasive approach to the intraperitoneal organs afforded by NOTES and real-time, in vivo acquisition of dynamic histological images.

Hemoglobin changes at the initiation of high-flux hemodialysis.

BACKGROUND: The aim of the present study was to assess hemoglobin changes occurring at the beginning of high-flux hemodialysis (HD). METHODS: In a group of 20 chronic HD patients (group A), total hemoglobin (tHb), hematocrit (Hct) and total serum proteins (TP) were measured in blood samples drawn from an arterial fistula needle before the initiation of high-flux HD, and from an arterial line 5 min after HD with the dialysate in the bypass mode. 31 chronic stable HD patients (group B) served as controls. In group B patients, tHb was measured in blood samples drawn from an arterial fistula needle before the initiation of high-flux HD, and from arterial and venous lines simultaneously 5 min later. Blood flow rates in groups A and B were set from the beginning of the study to 300 ml/min, while the bicarbonate dialysate flow rate and ultrafiltration rate in group B patients was set to 700 ml/min and zero, respectively. The same high-flux dialyzer was used for all patients (FLX-18, membrane PEPA 1.8 m(2)). RESULTS: A comparison of baseline (pre-dialysis) values with those derived from an analysis of the arterial line in groups A and B at 5 min revealed that tHb decreased by 0.6 +/- 0.2 g/dl (5.2 +/- 1.7%, p < 0.001) and 0.7 +/- 0.7 g/dl (5.4 +/- 6.2%, p < 0.001), respectively. At the same time, Hct and TP in group A decreased by 1.32 +/- 0.7% (3.8 +/- 2.0%, p <0.001) and 0.3 +/- 0.1 g/dl (4.8 +/- 1.4%, p < 0.001), respectively. Blood volume (BV) and plasma volume (PV) in group A patients at 5 min as calculated from tHb and TP values increased by 5.6 +/- 1.9 and 5.2 +/- 1.7%, respectively, while BV in group B patients increased by 6.1 +/- 7.0% (not significant when compared to group A). tHb did not change significantly in 14 patients (group C) studied immediately after adopting the supine position and 5 min later in the absence of HD. CONCLUSION: A 5% decrease in tHb was observed 5 min after the initiation of high-flux HD with a zero ultrafiltration rate, and was due to an increase in BV.

Clinical evaluation of four different high-flux hemodialyzers under conventional conditions in vivo.

Four types of high-flux hemodialyzers, Primus 2000 (high-flux polysulfone 2.0 m2), Altra-Flux 170 G (cellulose diacetate 1.7 m2), FLX-15 GW (polyester-polymer alloy 1.5 m2) and PAN-85 DX (polyacrylonitrile 1.7 m2) were evaluated in vivo. A total of 12 stable chronic hemodialysis patients participated in the study and each type of dialyzer was tested once in 9 of them. Blood samples for the measurement of BUN, creatinine, phosphate, uric acid, albumin and beta2-microglobulin (beta2M) were drawn before and 5 min after the end of the study dialysis. During dialysis, which was performed in all patients with a blood flow rate of 250 ml/min for 240 min, the dialysate (550-600 ml/min) was collected every hour and samples were drawn for the measurements of all the above substances. The mean total amount of low-molecular substances removed per session by each dialyzer was very close to 19.5 g for urea, 2.0 g for creatinine, 0.9 g for phosphate and 1 g for uric acid. The one-third (30-33%) of the above amounts were removed during the first hour of dialysis. Dialyzers' clearances for creatinine and uric acid were significantly higher in Primus dialyzer comparing to FLX-15 GW (p < 0.05) while the clearance for urea showed a borderline significance (p = 0.055). No difference was found either among Altra-Flux 170 G, FLX-15 GW and PAN-85 DX or between Primus and PAN-85 DX dialyzers. Phosphate clearance did not show any difference among the four dialyzers. The lowest amount of albumin removed per session was 0.75 g by PAN-85 DX and the highest 1.8 g by FLX-15 GW, while the equivalents for beta2M were 80 mg by Altra-Flux 170 G and 142 mg by PAN-85 DX. A significant adsorption of beta2M on these dialysis membranes was indicated by the combination of a satisfactory serum beta2M reduction ratio (post-/predialysis values = 0.52, 0.77, 0.60, 0.55) with a reduced beta2M clearance (23.9, 13.6, 20.2, 25.1 ml/min). During the first hour of dialysis, in comparison to the following time, the highest amounts of albumin and beta2M (expressed as percentage of total) were removed by the Primus 2000 dialyzer. Our results indicate that under conventional conditions small differences in the surface area of the high-flux dialyzers are unimportant regarding the removal of low molecules. However, the composition of the membrane seems to play an important role in the removal of high-molecular substances.

Urea concentration gradients during conventional hemodialysis.

To elucidate the intradialytic urea concentration gradients, we examined 26 hemodialysis patients wearing a double-lumen central venous catheter during their first or second fistula-punctured dialysis session. In 17 patients (group A), after 60 and 240 minutes of treatment with a mean blood flow of 196.4 +/- 9.9 mL/min, blood urea nitrogen (BUN) was measured in blood samples taken simultaneously from the central venous catheter, a vein in the arm opposite the access site, and the arterial and venous lines of the dialyzer. In 16 patients (group B), after 60 minutes of treatment with a mean blood flow rate of 197.5 +/- 12.3 mL/min, BUN was measured in blood samples taken from the dialyzer arterial line and then, after decreasing the blood flow to 50 to 60 mL/min for 1 minute, in samples taken from a vein in the arm opposite the access site, the central venous catheter, and the dialyzer arterial line. In group A, the mean BUN values in the dialyzer arterial line at 60 and 240 minutes were found to be 3.7% +/- 3.7% and 3.5% +/- 3.4% higher than the corresponding values in the central veins, respectively (P = NS between 60 and 240 minutes). In group B, after 1 minute of low blood flow, this difference was 1.5% +/- 2.4% (P = 0.06 compared with group A). The peripheral veins in group A patients at 60 and 240 minutes had 9.7% +/- 5.2% and 10.9% +/- 5.3% higher BUN values, respectively, compared with the central veins. This difference in group B patients after 1 minute of low blood flow was 6.8% +/- 4.2%. Urea access recirculation rate in group A, calculated by the classical three-samples method, was found to be 7.6% +/- 5.0% at 60 minutes and 9.9% +/- 5.8% at 240 minutes (P = NS). In group B, BUN values in the dialyzer arterial line after 1 minute of low blood flow increased significantly by 3.4% +/- 4.5% (P < 0.01). Our study shows that during conventional hemodialysis with a blood flow rate of 200 mL/min, urea concentration in the central veins is lower than in the dialyzer arterial line. This gradient after 1 minute of low-flow dialysis had a tendency to decrease. At the same time, however, the urea concentration gradient between the peripheral and central veins remained high, indicating that during conventional hemodialysis, intercompartmental disequilibrium plays a significant role in the arteriovenous gradient.

Efficacy of dual lumen jugular venous catheter hemodialysis when venous lumen is used as arterial lumen.

In 12 patients who underwent hemodialysis by a dual lumen jugular venous catheter, urea recirculation rate was measured during conventional treatment under normal conditions (R1), as well as when the venous lumen of the catheter was used as arterial lumen and the arterial as venous lumen (R2). Although the mean value of R2 was, as expected, higher than R1 (8.25 +/- 2.7 versus 4.25 +/- 1.00; p = 0.0004), it was still within the acceptable rate. We conclude that during hemodialysis by a dual lumen jugular venous catheter, efficient treatment can be provided when the venous is used as arterial lumen.

[Chronic hemodialysis in a patient with AIDS]. / Chronia aimokatharse se asthenos me AIDS.

In this paper, we report our experience concerning chronic dialysis treatment in a patient with AIDS. We describe also all necessary precautions we utilized to prevent virus transmission from the patient to the staff. The latter was achieved with the use of standard gown, mask and gloves, as well as the use of plastic face shield. In addition, all disposable materials used, such as needles etc., were placed in special containers by the end of each hemodialysis session. Fistula puncture was done with great care and both needles were inserted to the same direction (towards the shoulder). Dialysis machine was sterilized by and was not dedicated only to this patient. No seroconversion was observed, up to now, among dialysis staff. Dialysis of AIDS patients should be performed with extremely special precautions in order to avoid unnecessary hazards to the staff.