Standard Clinical Outcomes, Light Distortion, Stereopsis, and a Quality-of-Life Assessment of a New Binocular System of Complementary IOLs.

PURPOSE: To evaluate the visual outcome, light distortion index (LDI), and quality of life (QoL) of patients implanted with two complementary intraocular lenses (IOLs) to treat cataract and presbyopia. METHODS: Twenty-seven consecutive patients with cataract were treated with the implantation of the Artis Symbiose Mid (Mid) IOL (Cristalens Industrie) in the distance-dominant eye and the Artis Symbiose Plus (Plus) IOL (Cristalens Industrie) in the contralateral eye following phacoemulsification. The primary objective was to ascertain the monocular and binocular defocus curves. Secondary endpoints included uncorrected distance visual acuity, corrected distance visual acuity, uncorrected intermediate visual acuity, and distance-corrected intermediate visual acuity at 90 and 70 cm, uncorrected near visual acuity and distance-corrected visual acuity at 40 cm, contrast sensitivity, LDI with a halometer, stereopsis, and patients' QoL with the validated Visual Function Index (VF-14) questionnaire. These measurements were collected in two visits, at 4.14 ± 3.13 and 10.30 ± 3.14 months postoperatively. RESULTS: Statistically significant differences in the monocular defocus curves were found at the defocus steps of -1.00, -1.25, -1.50, -1.75, -2.50, -2.75, -3.00, -3.50 diopters and the -4.00 diopters (P < .050). The mean binocular defocus curve was 0 logMAR or better from the +0.50 to the -2.50 D defocus steps. Contrast sensitivity was within normal values. The LDI was 12.57 (6.61)% for the Mid eyes, 14.99 ± 5.70% for the Plus eyes, and 10.36 ± 4.42% binocularly. The patients' stereopsis was 40.0 (12.5) arc-seconds. The QoL score was 95.99 (7.14) at 10 months. CONCLUSIONS: The implantation of the Artis Symbiose IOLs was a safe and effective treatment for presbyopia compensation in patients with cataract. Both IOLs are complementary and may produce a binocular depth-of-field of 3.00 diopters over 0 logMAR when used together. [J Refract Surg. 2023;39(10):654-661.].

On the protective role of the blood vessels in glaucomatous damage: A transversal study

Purpose: To corroborate whether vessels on the surface of the optic nerve head can provide protection against the loss of underlying axons in subjects with manifest glaucoma.MethodsIn this pilot study, thirty-six glaucomatous eyes with a perimetric defect in the Bjerrum area were included. The retinal nerve fiber layer (RNFL) thickness was measured in each of the sectors of the clock-hour map obtained by Cirrus HD-OCT considering the presence or absence of blood vessels. These sectors were related with their corresponding areas of the retina examined in the visual field using a mathematical model of the retina introduced by Jansonius, in order to determine the values of threshold sensitivity in those areas in the presence or absence of vessels.ResultsWe corroborated the protective role of the blood vessel for peripapillary RNFL thickness of clock-hour 12 despite obtaining a p-value (p = 0.023; w = 228.5) close to the acceptance zone (p ≥ 0.05). The mean ± standard deviation with vessel and without vessel were 70.95 ± 24.35 and 88.46 ± 23.96, respectively. No differences were found between the mean values of threshold sensitivity to the presence or absence of blood vessels in each of the sectors considered.ConclusionsOur findings do not allow us to affirm that there is an association between the presence of a vessel and protection against glaucomatous damage in subjects with an advanced manifestation of the disease. In the future, more extensive studies are needed to study this relationship in subjects with early glaucoma. (AU)

On the protective role of the blood vessels in glaucomatous damage: A transversal study.

PURPOSE: To corroborate whether vessels on the surface of the optic nerve head can provide protection against the loss of underlying axons in subjects with manifest glaucoma. METHODS: In this pilot study, thirty-six glaucomatous eyes with a perimetric defect in the Bjerrum area were included. The retinal nerve fiber layer (RNFL) thickness was measured in each of the sectors of the clock-hour map obtained by Cirrus HD-OCT considering the presence or absence of blood vessels. These sectors were related with their corresponding areas of the retina examined in the visual field using a mathematical model of the retina introduced by Jansonius, in order to determine the values of threshold sensitivity in those areas in the presence or absence of vessels. RESULTS: We corroborated the protective role of the blood vessel for peripapillary RNFL thickness of clock-hour 12 despite obtaining a p-value (p = 0.023; w = 228.5) close to the acceptance zone (p ≥ 0.05). The mean ± standard deviation with vessel and without vessel were 70.95 ± 24.35 and 88.46 ± 23.96, respectively. No differences were found between the mean values of threshold sensitivity to the presence or absence of blood vessels in each of the sectors considered. CONCLUSIONS: Our findings do not allow us to affirm that there is an association between the presence of a vessel and protection against glaucomatous damage in subjects with an advanced manifestation of the disease. In the future, more extensive studies are needed to study this relationship in subjects with early glaucoma.

An Ultrasonic Tomography System for the Inspection of Columns in Architectural Heritage.

A new versatile and geometrically reconfigurable ultrasonic tomography system (UTS) has been designed to inspect and obtain information about the internal structure and inner damage of columns in heritage buildings. This nondestructive system is considered innovative because it aims to overcome common limitations of existing systems. Tomographic inspections are typically carried out manually and are thus limited to small portions of construction elements. The proposed UTS allows the automatization of the inspection and the generation of numerous tomographic slices along the height of the column. It is valid for multiple types of columns and materials. In the present work, the system was tested on two limestone columns of the north façade of the Convent of Carmo in Lisbon, Portugal. The UTS is composed of a mechanical and an electronic system. The mechanical system consists of four linear motion subsystems mounted in a square setup. A transducer is placed on each of the axes, acting as emitter or receiver of the ultrasonic signals. The mechanical system also includes a guide system to adapt the inspections to the complex geometry of the columns. The electronic system allows the control and the synchronization of the movements and the emission/reception configuration of the four ultrasonic transducers.

Utility of Big Data in Predicting Short-Term Blood Glucose Levels in Type 1 Diabetes Mellitus Through Machine Learning Techniques.

Machine learning techniques combined with wearable electronics can deliver accurate short-term blood glucose level prediction models. These models can learn personalized glucose-insulin dynamics based on the sensor data collected by monitoring several aspects of the physiological condition and daily activity of an individual. Until now, the prevalent approach for developing data-driven prediction models was to collect as much data as possible to help physicians and patients optimally adjust therapy. The objective of this work was to investigate the minimum data variety, volume, and velocity required to create accurate person-centric short-term prediction models. We developed a series of these models using different machine learning time series forecasting techniques suitable for execution within a wearable processor. We conducted an extensive passive patient monitoring study in real-world conditions to build an appropriate data set. The study involved a subset of type 1 diabetic subjects wearing a flash glucose monitoring system. We comparatively and quantitatively evaluated the performance of the developed data-driven prediction models and the corresponding machine learning techniques. Our results indicate that very accurate short-term prediction can be achieved by only monitoring interstitial glucose data over a very short time period and using a low sampling frequency. The models developed can predict glucose levels within a 15-min horizon with an average error as low as 15.43 mg/dL using only 24 historic values collected within a period of sex hours, and by increasing the sampling frequency to include 72 values, the average error is reduced to 10.15 mg/dL. Our prediction models are suitable for execution within a wearable device, requiring the minimum hardware requirements while at simultaneously achieving very high prediction accuracy.

On the Possibility of Predicting Glycaemia 'On the Fly' with Constrained IoT Devices in Type 1 Diabetes Mellitus Patients.

Type 1 Diabetes Mellitus (DM1) patients are used to checking their blood glucose levels several times per day through finger sticks and, by subjectively handling this information, to try to predict their future glycaemia in order to choose a proper strategy to keep their glucose levels under control, in terms of insulin dosages and other factors. However, recent Internet of Things (IoT) devices and novel biosensors have allowed the continuous collection of the value of the glucose level by means of Continuous Glucose Monitoring (CGM) so that, with the proper Machine Learning (ML) algorithms, glucose evolution can be modeled, thus permitting a forecast of this variable. On the other hand, glycaemia dynamics require that such a model be user-centric and should be recalculated continuously in order to reflect the exact status of the patient, i.e., an 'on-the-fly' approach. In order to avoid, for example, the risk of being disconnected from the Internet, it would be ideal if this task could be performed locally in constrained devices like smartphones, but this would only be feasible if the execution times were fast enough. Therefore, in order to analyze if such a possibility is viable or not, an extensive, passive, CGM study has been carried out with 25 DM1 patients in order to build a solid dataset. Then, some well-known univariate algorithms have been executed in a desktop computer (as a reference) and two constrained devices: a smartphone and a Raspberry Pi, taking into account only past glycaemia data to forecast glucose levels. The results indicate that it is possible to forecast, in a smartphone, a 15-min horizon with a Root Mean Squared Error (RMSE) of 11.65 mg/dL in just 16.15 s, employing a 10-min sampling of the past 6 h of data and the Random Forest algorithm. With the Raspberry Pi, the computational effort increases to 56.49 s assuming the previously mentioned parameters, but this can be improved to 34.89 s if Support Vector Machines are applied, achieving in this case an RMSE of 19.90 mg/dL. Thus, this paper concludes that local on-the-fly forecasting of glycaemia would be affordable with constrained devices.

Variables to Be Monitored via Biomedical Sensors for Complete Type 1 Diabetes Mellitus Management: An Extension of the "On-Board" Concept.

Type 1 diabetes mellitus (DM1) is a growing disease, and a deep understanding of the patient is required to prescribe the most appropriate treatment, adjusted to the patient's habits and characteristics. Before now, knowledge regarding each patient has been incomplete, discontinuous, and partial. However, the recent development of continuous glucose monitoring (CGM) and new biomedical sensors/gadgets, based on automatic continuous monitoring, offers a new perspective on DM1 management, since these innovative devices allow the collection of 24-hour biomedical data in addition to blood glucose levels. With this, it is possible to deeply characterize a diabetic person, offering a better understanding of his or her illness evolution, and, going further, develop new strategies to manage DM1. This new and global monitoring makes it possible to extend the "on-board" concept to other features. This well-known approach to the processing of variable "insulin" describes some inertias and aggregated/remaining effects. In this work, such analysis is carried out along with a thorough study of the significant variables to be taken into account/monitored-and how to arrange them-for a deep characterization of diabetic patients. Lastly, we present a case study evaluating the experience of the continuous and comprehensive monitoring of a diabetic patient, concluding that the huge potential of this new perspective could provide an acute insight into the patient's status and extract the maximum amount of knowledge, thus improving the DM1 management system in order to be fully functional.

Ultrasound Transmission Tomography for Detecting and Measuring Cylindrical Objects Embedded in Concrete.

This study explores the feasibility of using transmission tomographic images based on attenuation measures in transmission to detect and estimate the most common materials that are embedded in concrete, reinforcements and natural and artificial voids. A limited set of concrete specimens have been made in which cylindrical objects such as bars/tubes of steel, PVC and aluminium have been embedded to analyse the effect of size and material. The methodology and scope of this study is presented and numerical simulations are carried out to optimize the emitter-receiver configuration and to understand the complex physical propagation phenomena of ultrasonic signals that travel through concrete with embedded inclusions. Experimental tomographic images are obtained by using an ultrasonic tomographic system, which has the advantage of needing only two ultrasonic transducers. Both the software simulation tool and the tomographic inspection system are developed by the authors. The obtained results show that PVC tubes and steel bars of diameters higher than 19 mm and embedded in cylindrical specimens, can be detected and their sizes estimated using segmented tomographic images.

Routing Topologies of Wireless Sensor Networks for Health Monitoring of a Cultural Heritage Site.

This paper provides a performance evaluation of tree and mesh routing topologies of wireless sensor networks (WSNs) in a cultural heritage site. The historical site selected was San Juan Bautista church in Talamanca de Jarama (Madrid, Spain). We report the preliminary analysis required to study the effects of heating in this historical location using WSNs to monitor the temperature and humidity conditions during periods of weeks. To test which routing topology was better for this kind of application, the WSNs were first deployed on the upper floor of the CAEND institute in Arganda del Rey simulating the church deployment, but in the former scenario there was no direct line of sight between the WSN elements. Two parameters were selected to evaluate the performance of the routing topologies of WSNs: the percentage of received messages and the lifetime of the wireless sensor network. To analyze in more detail which topology gave the best performance, other communication parameters were also measured. The tree topology used was the collection tree protocol and the mesh topology was the XMESH provided by MEMSIC (Andover, MA, USA). For the scenarios presented in this paper, it can be concluded that the tree topology lost fewer messages than the mesh topology.

Trabectedin in pre-treated patients with advanced or metastatic soft tissue sarcoma: a phase II study evaluating co-treatment with dexamethasone.

PURPOSE: This study assesses the efficacy, toxicity and pharmacokinetic profile of trabectedin with or without prophylactic dexamethasone co-treatment in patients with recurrent advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Patients were randomized to receive trabectedin as a 3-h infusion every 3 weeks with dexamethasone or placebo in the first cycle, with the alternate in the second cycle and with the patient's choice subsequently. Due to toxicity, the randomized design was modified to open-label to make dexamethasone mandatory and the initial dose (1,650 µg/m(2)) was reduced to 1,500 µg/m(2) and then to 1,300 µg/m(2). RESULTS: Forty-one patients were enrolled and 35 were evaluable for efficacy. One partial response and 18 disease stabilizations were found. The median PFS and OS were 2.1 and 10.2 months, respectively, with the 3- and 6-month PFS rates indicating activity in pretreated STS. Twenty-three and 27 patients developed transient asymptomatic grade 3/4 AST and ALT elevation, respectively, and 21 patients had grade 3/4 neutropenia. Dose reduction from 1,650 µg/m(2) to 1,300 µg/m(2) decreased the incidence of grade 3/4 thrombocytopenia (26% vs. 0%), neutropenia (51% vs. 25%) and AST increase (76% vs. 25% of patients). Four patients died due to drug-related toxicities (3 with placebo). The total body clearance of trabectedin was 28% higher and half-life was 21% lower with dexamethasone compared to placebo, with no differences in volume of distribution. CONCLUSIONS: Trabectedin has confirmed activity in patients with pretreated STS. This study shows that co-treatment with dexamethasone improves the safety of trabectedin by reducing drug-induced hepatotoxicity and myelosuppression.

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PURPOSE: A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. EXPERIMENTAL DESIGN: Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. RESULTS: Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. CONCLUSIONS: The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

Semimechanistic pharmacokinetic/pharmacodynamic model for hepatoprotective effect of dexamethasone on transient transaminitis after trabectedin (ET-743) treatment.

PURPOSE: Reversible transient elevations in transaminases have been observed after trabectedin administration. A semimechanistic pharmacokinetic and pharmacodynamic (PKPD) model was developed to evaluate the time course of alanine aminotransferase (ALT) elevation, tolerance development, and the hepatoprotective effect of dexamethasone on trabectedin-induced transient transaminitis following different dosing schedules in cancer patients. PATIENTS AND METHODS: Trabectedin was administered to 711 patients as monotherapy (dose range: 0.024-1.8 mg/m(2)) as 1-, 3-, or 24-h infusions every 21 days; 1- or 3-h infusions on days 1, 8, and 15 every 28 days; or 1-h infusions daily for five consecutive days every 21 days. Population PKPD modeling was performed with covariate evaluation [dexamethasone use (469/711 pt), ECOG performance status scores (89.7% pts or=3 toxicity by 13 and 39% following two and four cycles of therapy, respectively. CONCLUSIONS: A PKPD model quantifying the hepatoprotective effect of dexamethasone on transient and reversible transaminitis following trabectedin treatment has been developed. The model predicts that co-administration of dexamethasone and the suggested dose reduction strategy based on the serum concentration of liver enzymes will enhance the safe use of trabectedin in the clinic.

Phase II study of plitidepsin in pretreated patients with locally advanced or metastatic non-small cell lung cancer.

OBJECTIVE: To evaluate the progression-free rate (PFR) at 3 months (13+/-1 weeks), antitumor response, time-to-event efficacy endpoints, and toxicity profile of plitidepsin administered as a 3-h continuous i.v. infusion at a dose of 5mg/m(2), every 2 weeks, to patients with chemotherapy pretreated advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This was a multicenter, non-randomized, exploratory, phase II study. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. PFR (primary efficacy endpoint) and objective response rate (secondary efficacy endpoint) were evaluated according to RECIST, while the toxic profile of plitidepsin was assessed using the NCI-CTC, version 2.0. RESULTS: A total of 21 patients with a median age of 61 years and with locally advanced or metastatic non-resectable NSCLC, who had previously received only one line of chemotherapy in an advanced setting, received a total of 54 cycles of treatment (median of two cycles per patient; range: 1-8). Antitumor activity was seen in 3 (1 PR, 2 SD) out of 17 evaluable patients according to RECIST. One patient was responder for the primary (PFR at 13+/-1 weeks) and secondary efficacy endpoint (stable disease according to RECIST). Other two patients were non-responders for the primary efficacy endpoint, but had stable disease (not confirmed at weeks 13+/-1 due to previous withdrawal due to adverse events). With a median follow-up of 12.3 months, the median time to progression (TTP) and the median overall survival (OS) were 1.2 months and 4.3 months, respectively. The incidence of plitidepsin-related toxicities was low and most of them were mild-to-moderate in severity. The most common side effects were anemia, and asymptomatic and non-cumulative increases of gamma-glutamyltransferase (GGT) and liver transaminase levels. CONCLUSION: This study shows that plitidepsin 3-h continuous i.v. infusion (5mg/m(2)) every 2 weeks, was feasible and well tolerated in patients with pretreated NSCLC. The lack of evidence of antitumor activity precludes further studies with this plitidepsin schedule in this tumor setting.

Phase II study of trabectedin in pretreated patients with advanced colorectal cancer.

PURPOSE: This open-label, nonrandomized, phase II study was aimed at evaluating the efficacy and toxicity of trabectedin over a 3-hour intravenous infusion every 3 weeks in patients with pretreated advanced colorectal cancer. PATIENTS AND METHODS: Twenty-one patients were enrolled: 5 patients (23.8%) were treated with 1650 microg/m(2), 10 patients (47.6%) with 1300 microg/m(2), and 6 patients (28.6%) with 1100 microg/m(2). Response to treatment was assessed according to World Health Organization criteria, and toxicities were graded according to National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS: The median number of treatment cycles per patient was 2 (range, 1-6 cycles). No objective responses were reported. Four patients (19%; 95% confidence interval [CI], 5.5%-41.9%) exhibited stable disease lasting for a median of 3.6 months (range, 2.4-4.9 months). The median time to progression was 1.5 months (95% CI, 1.3-1.6 months), and the median overall survival was 4.4 months (95% CI, 3-7.5 months; n=2 censored). The main grade 3/4 toxicities were transient asymptomatic transaminase increase (alanine aminotransferase, 66.7% of patients; aspartate aminotransferase, 57.1%) and neutropenia (42.8%). No toxic deaths were reported. CONCLUSION: Trabectedin 1300 microg/m(2) given as a 3-hour intravenous infusion every 3 weeks was well tolerated but lacked activity in pretreated advanced-stage colorectal cancer. Therefore, further clinical trials with this trabectedin schedule as a single agent are not warranted.

Perfil de los pacientes ingresados en UCI con cetoacidosis diabética / Profile of patients with diabetic ketoacidosis in the intensive care unit

Objetivo: Valoración de pacientes ingresados en una unidad de cuidados intensivos (UCI) con el diagnóstico de cetoacidosis diabética (CAD). Método: Revisión de los casos ingresados durante 5 años. Se analizan características clínicas, factores contribuyentes, datos de laboratorio y factores pronósticos. Resultados: Treinta pacientes han justificado 38 episodios de CAD. Hay un predominio de los varones, de los ingresos en primavera y otoño y de antecedentes de diabetes mellitus. Los factores precipitantes son: desconocidos (28,9%), infecciosos (28,9%), omisión o inadecuado tratamiento con insulina (15,8%), drogadicción (15,8%) y enfermedad intercurrente (10,4%). Ningún paciente presentó al ingreso un índice de Glasgow Coma Score (GCS) < 9. Un 7,9% presentó hipotensión, sin necesidad de fármacos vasoactivos. Los valores bioquímicos medios al ingreso fueron: glucemia, 649 ± 304 mg/dl; pH, 7,04 ± 0,12; bicarbonato, 6,26 ± 3,9 mEq/l; leucocitos, 16.532 ± 6.948 µl; sodio, 135 ± 8 mEq/l; potasio, 4,9 ± 1,2 mEq/l; creatinina, 1,9 ± 0,9 mg/dl. Los días de estancia media en UCI fueron 3, con menos de 2 días en la mitad de los pacientes. Las complicaciones graves más frecuentes fueron edema cerebral (2,6%), accidente cerebrovascular agudo (ACVA) (2,6%), pancreatitis (2,6%) e insuficiencia respiratoria (5,3%). Falleció el 13,2% de los ingresados. Los pacientes que desarrollaron edema cerebral, insuficiencia respiratoria y ACVA justifican el 80% de las muertes. Otras variables relacionadas fueron edad, potasio y pH al ingreso, y días de estancia. Conclusiones: En nuestro entorno la CAD predomina en varones, y en primavera y otoño. La mayoría de los pacientes son diabéticos conocidos con una causa conocida de precipitación. El control de los pacientes es bueno y la evolución, adecuada, salvo que aparezcan complicaciones como edema cerebral/ACVA o insuficiencia respiratoria (AU)

Objective: To determine the clinical characteristics of patients admitted to the intensive care unit (ICU) with a diagnosis of diabetic ketoacidosis (DKA). Method: We performed a retrospective chart review of all patients admitted to our ICU over a 5-year period with a diagnosis of DKA. The medical records were analyzed to identify clinical presentations, contributory factors, laboratory data, and outcomes. Results: Data on 30 patients with 38 DKA episodes were included. Patients were predominantly men. Episodes were more frequent in the spring and fall. Most patients had established diabetes. Precipitating factors of DKA were unknown in 28.9%, infections in 28.9%, omission of insulin therapy or inadequate insulin therapy in 15.8%, polysubstance abuse in 15.8%, and medical illness in 10.4%. All patients had a Glasgow Coma Scale >= 9. Mild hypotension was found in 7.9%, without the need for vasoactive drugs. The mean laboratory values at admission were as follows: glucose 649 ± 304 mg/dl; pH 7.04 ± 0.12; bicarbonate 6.26 ± 3.9 mEq/l; white blood cell count 16,532 ± 6,948 µl; sodium 135 ± 8 mEq/l; potassium 4.9 ± 1.2 mEq/l; creatinine 1.9 ± 0.9 mg/dl. The mean length of stay in the ICU was 3 days and more than half the patients were admitted for less than 2 days. The most frequent severe complications were cerebral edema in 2.6%, ischemic cerebrovascular disease in 2.6%, pancreatitis in 2.6%, and respiratory failure in 5.3%. A total of 13.2% of the patients died in the ICU. The main predictors of mortality were cerebral edema, respiratory failure and ischemic cerebrovascular disease, accounting for 80% of deaths. Mortality was also influenced by age, potassium levels, pH, and length of stay. Conclusions: In our environment, DKA was more frequent in men and in the spring and fall. Most patients had established diabetes and a known precipitating factor. Outcome was favorable in patients without complications such as cerebral edema, ischemic cerebrovascular disease, or respiratory failure (AU)

A phase I clinical and pharmacokinetic study of paclitaxel and docetaxel given in combination in patients with solid tumours.

The aim of this study was to determine the safety and feasibility profile of paclitaxel (PTX) and docetaxel (DTX) in combination and the pharmacokinetic and pharmacodynamic interaction between these two drugs in two different alternated sequences of administration. The starting dose was PTX (100 mg/m(2)) as a 3-h IV infusion followed by DTX (50 mg/m(2)) as 1-h IV infusion or the alternative sequence in every other patient. The sequence was alternated in the second course in each patient treated. Cycle duration was 21 days. Twenty patients received 103 cycles of treatment through three dose levels. Febrile neutropenia and grade 4 neutropenia lasting longer than 7 days were dose-limiting and defined the toxic dose of DTX (50 mg/m(2)) and PTX (135 mg/m(2)) in patients with prior treatment and the recommended dose in patients without prior treatment. Non-hematological toxicities included asthenia, neuropathy, arthralgia/myalgia and stomatitis. Pharmacokinetics of DTX were significantly affected by the sequence. Nadir ANC was more profound when DTX was administered first (P=0.022). There were one complete response and six partial responses, giving an overall response rate of 35%. DTX (50 mg/m(2)) followed by PTX (135 mg/m(2)) can be administered safely and it is an active regimen. The pharmacokinetics of PTX are not influenced by DTX but DTX pharmacokinetics depend on the sequence of administration, which influences its haematological toxicity profile.