Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Effect of alcohol intake and cigarette smoking on sperm parameters and pregnancy.

Much has been published about smoking and alcohol intake influencing male fertility, sperm parameters and reproductive outcome. However, there is no conclusive agreement about the effects of cigarette smoking and alcohol use on these outcomes and thus no generally accepted guidelines. The combined effect of cigarette smoking and alcohol intake, though, has not been rigorously investigated. Because alcohol consumption and smoking are often seen together, this study focuses on the effect of smoking and drinking habits separately and combined on semen parameters, such as volume, sperm count, motility and morphology, and on pregnancy outcome. These suggested toxic effects are studied in a group of subfertile, asthenozoospermic men (<10% motile spermatozoa), compared with a group of 'proven fertile', healthy men. The extreme asthenozoospermic group has especially been chosen because of the suspected effect, that is, oxidative stress, on sperm motility. In our study, we found that cigarette smoking and alcohol intake did not differ between the subfertile and fertile group. In conclusion, cigarette smoking and alcohol consumption do not appear to significantly affect sperm parameters, such as volume, sperm count, motility and morphology or pregnancy outcome in our study population.

Metabolomic profiling by near-infrared spectroscopy as a tool to assess embryo viability: a novel, non-invasive method for embryo selection.

BACKGROUND: The morphology of an embryo has a limited predictive value for assessing viability and ongoing pregnancy, therefore new selection tools are needed to maintain success rates with single-embryo transfer (SET). In this study, we investigated if metabolomic profiling of biomarkers of embryo culture medium by near-infrared (NIR) spectroscopy has a correlation with ongoing pregnancy in SET. METHODS: A total of 333 patients scheduled for in vitro fertilization (IVF) with SET were included in the study. Embryos were selected for transfer by morphological criteria on Days 2 and 3 of in vitro culture, and left over culture media samples were analyzed by NIR spectroscopy. RESULTS: The NIR spectral analysis produced unique metabolomic profiles that correlated to an embryo's reproductive potential. Resulting relative viability scores between positive and negative pregnancy outcomes were statistically significant (P < 0.03). A logistic regression of factors correlated to pregnancy outcomes showed that maternal age, percent fragmentation and relative viability scores all demonstrated a relationship. The extent of the correlation was determined by accuracy computation, where the accuracy of assessing viable embryos on Day 3 by metabolomic profiling was 53.6% and the accuracy of the morphological selection was 38.5%. In addition, the positive predictive value of metabolomic profiling was 0.365 and the negative predictive value was 0.830. CONCLUSIONS: NIR metabolomic profiling of spent embryo culture media was able to distinguish viable embryos from non-viable embryos for reproduction.

Evolución del tratamiento y consumo en personas con dependencia de la cocaína, a los doce meses, en función de la psicopatología asociada y el funcionamiento cotidiano / Evolution of treatment and consumption in persons with cocaine dependence, at 12-months, in respect of the associated psychopathology and daily functioning

El objetivo del presente estudio es analizar la evolución, a los doce meses, de personas con dependencia de la cocaína que están en tratamiento en Centros de Drogodependencias. Analizamos si hay relación entre variables sociodemográficas, características del consumo de drogas y características psicopatológicas con el mantenimiento de la abstinencia y la evolución del funcionamiento cotidiano evaluado por el terapeuta a los tres, seis y doce meses. Los resultados más destacados son que las personas con un patrón de personalidad dependiente, según el MCMI-II, tienen una mayor probabilidad de mantener la abstinencia en el consumo de cocaína durante los doce meses que siguen a la evaluación inicial. Las variables que están más relacionadas con un peor funcionamiento cotidiano a los doce meses son el consumo de cocaína por vía inyectada o fumada, la realización de tratamientos previos por consumo de drogas y haber consumido heroína en alguna ocasión. Por lo tanto, aspectos relacionados con el consumo de drogas y no características psicopatológicas son más importantes al analizar la evolución a los doce meses

The aim of the present study is to analyse the evolution, at 12-months, of patients with cocaine dependence undergoing treatment in drug abuse centres. We examined the relationship between sociodemographic variables, drug use characteristics, and psychopathological characteristics with maintenance of drug abstinence and the evolution of daily functioning evaluated by the therapist at 3-, 6- and 12-months. The most outstanding results are that subjects with a dependent personality pattern, according to the MCMI-II, are more likely to maintain cocaine abstinence during the 12-months following the preliminary assessment. Moreover, the variables more related with a worse daily functioning at 12-months are injected or smoked cocaine use, previous treatments for drug use and having used heroin on some occasion. Therefore, drug related aspects and not psychopathological characteristics are more important when analysing the 12-months evolution in these subjects

Dependencia de la cocaína y trastornos de personalidad. Análisis de su relación en una muestra clínica / Cocaine dependence and personality disorders. Analysis in a clinical sample

Objetivo. Los trastornos de personalidad en personas con dependencia de la cocaína son frecuentes e interfieren en el tratamiento de estas personas. En España todavía son escasos los estudios que se ocupan de evaluar esta relación. El objetivo del presente estudio es evaluar la presencia de trastornos de personalidad en personas con dependencia de la cocaína que están en tratamiento en Centros de Drogodependencias, y conocer si hay diferencias entre los sujetos que tienen trastornos de personalidad y los que no los tienen, en función de características sociodemográficas, psicopatológicas y de consumo de drogas. Material y métodos. Utilizamos el MCMI-II para analizar la probabilidad de presencia de trastornos de personalidad. El estudio se realizó en 102 pacientes con dependencia de la cocaína. Resultados. Un importante porcentaje de los sujetos presenta, al menos, un trastorno de personalidad (66,6%). Estos se diferencian del grupo de sujetos que no tienen trastorno de personalidad en las características psicopatológicas analizadas (depresión, ansiedad, etc.). Conclusiones. La importante prevalencia de los trastornos de personalidad en personas con dependencia de la cocaína indica la necesidad de su evaluación al inicio del tratamiento

Objective. The personality disorders in people with cocaine dependence are frequent and they interfere in the treatment of these persons. Few studies analyze this relationship in Spain. The present study aims to evaluate the presence of personality disorders in persons with cocaine dependence that are in treatment in Centers of Drug Dependence in Galicia (Spain) and to know if there are differences among both groups, with and without personality disorders, in relation to sociodemographic characteristics, psychopathology and drug consumption. Material and methods. We use the MCMI-II to analyze the probability of presence of personality disorders. One hundred and two patients with cocaine dependence were included in the study. Results. An important percentage of subjects present one or more personality disorder (66.6%), and they differ of the group without personality disorders in psychopathological characteristics (depression, anxiety, etc.). Conclusions. The important prevalence of personality disorders in cocaine dependence persons indicates the evaluation to the beginning of treatment

The postwash total progressively motile sperm cell count is a reliable predictor of total fertilization failure during in vitro fertilization treatment.

OBJECTIVE: To predict the chance of total fertilization failure (TFF) before the day of ovum pickup with known semen and female variables. DESIGN: A statistical model was constructed to predict TFF by retrospective analysis (2,366 couples) and subsequently tested on a new IVF population (917 couples). SETTING: Academic tertiary referral center. PATIENT(S): Three thousand three hundred eighty-three couples who underwent an IVF-ET treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The ability to predict the probability of TFF in IVF. RESULT(S): Two variables-postwash total progressively motile sperm cell count (postwash TPMC) and number of follicles-were found to be significant. Taking a probability of 25% as an acceptable risk of TFF, we calculated that a postwash TPMC of <1.1 x 10(6) cells results in a risk of TFF of >25%. Low responders (<4 follicles) needed a postwash TPMC of >2.2 x 10(6) cells to reduce the risk of TFF to <25%. High responders (>15 follicles) needed only 0.35 x 10(6) postwash progressively motile spermatozoa. CONCLUSION(S): When postwash TPMC and number of follicles are known and an unacceptable TFF outcome is expected, one can propose an ICSI procedure a few days before the day of ovum pickup.

Only hydrosalpinges visible on ultrasound are associated with reduced implantation and pregnancy rates after in-vitro fertilization.

A retrospective analysis of clinical and laboratory data was made of all in-vitro fertilization (IVF) patients with tubal pathology who had their first ever embryo transfer cycle between January 1st, 1992 and September 1st, 1996. The aim of the study was to determine the effect of the presence of a hydrosalpinx, whether or not visible by ultrasound, on pregnancy, multiple pregnancy and implantation rates in our patient population. The IVF success rate was also analysed by calculating cumulative ongoing pregnancy rates of the same patient group using the lifetime table approach. In the presence of an ultrasound-visible hydrosalpinx, rates of pregnancy and multiple pregnancy appeared reduced, but the differences were not significant. The rates of implantation, clinical implantation and ongoing implantation were significantly lower in the presence of an ultrasound-visible hydrosalpinx (odds ratios 0.33-0.46, C.I. 0.21-0.96). The cumulative chance of achieving an ongoing pregnancy after one or more IVF cycles was significantly reduced in the presence of an ultrasound-visible hydrosalpinx (relative hazard 0.36, C.I. 0.22-0.59). In the presence of a hydrosalpinx not visible by ultrasound the IVF outcome was not reduced. This retrospective study confirms that patients with hydrosalpinges have an impaired IVF outcome. Unique to this study and previously unobserved is the finding that there is a subgroup of patients with hydrosalpinges, those with ultrasound-visible hydrosalpinges, which is exclusively responsible for this impaired outcome.

Preparation of heparin-like surfaces by introducing sulfate and carboxylate groups on poly(ethylene) using an argon plasma treatment.

Carboxylate and sulfate groups were introduced at the surface of poly(ethylene) (PE) samples. This was accomplished by coating and immobilizing sodium 10-undecenoate (C11(:)) and 10-undecene sulfate (S11(:)) on the polymer by means of an argon plasma treatment. The composition of the coated surfactant layer was proportional to the composition of the coating solution. The thickness of the surfactant layer on the surface of PE samples, which were precoated from an aqueous solution with a total surfactant concentration of 0.30 M, was about 55 A. The presence of carboxylate and sulfate groups after plasma treatment of the precoated surfaces was confirmed by X-ray photoelectron spectroscopy (XPS). About 20% of the initial amount of functional groups of the coated surfactants was retained at the PE surface. The ratio of carboxylate/sulfate groups at the plasma treated surfaces was dependent on the composition of the precoated surfaces. The minimum surface density of these groups on the resulting samples was about one group per 40 A2.

Heparinization of gas plasma-modified polystyrene surfaces and the interactions of these surfaces with proteins studied with surface plasmon resonance.

Polystyrene surfaces obtained by spin-coating a solution of polystyrene in toluene on a gold layer were functionalized with carboxylic acid groups by preadsorption of the sodium salt of undecylenic acid, followed by an argon plasma treatment. A conjugate of albumin and heparin (alb-hep) was covalently immobilized onto the functionalized surface via preactivation of carboxylic acid groups with a water-soluble carbodiimide. The immobilization of alb-hep conjugate and the subsequent interactions of the heparinized surface with antithrombin III (ATIII, a heparin cofactor) and thrombin were monitored with surface plasmon resonance (SPR). The surface concentration of conjugate as determined with SPR deviated quantitatively from the results obtained with radiolabelled conjugate. The difference in surface concentrations of conjugate obtained with the two methods probably originates from the uncertainty of the refractive index of the alb-hep conjugate in the SPR technique. ATIII could be bound to the surface modified with alb-hep conjugate but not to a polystyrene surface modified with albumin. Rabbit anti-human ATIII did bind to the alb-hep surface previously exposed to ATIII, confirming the presence of surface bound ATIII. The alb-hep immobilized surface was able to bind much more thrombin than ATIII, which is probably due to the less specific heparin-thrombin interaction as compared to the heparin-ATIII interaction. This study shows that SPR is a technique that can be used to study, in real time, both the modification of polymer surfaces and the subsequent interactions of the modified surfaces with proteins.

Immobilization of functionalized alkyl-poly(ethylene oxide) surfactants on poly(ethylene) surfaces by means of an argon plasma treatment.

Alkyl-poly(ethylene oxide) (PEO) surfactants containing a terminal hydroxyl, sulfate, or carboxylate group were grafted at the surface of poly(ethylene) (PE) samples to improve their blood compatibility. Grafting was achieved by immobilizing PEO surfactants on PE using an argon plasma treatment. The sulfate group containing PEO surfactant was synthesized by sulfating polyoxyethylene(20)stearylether (Brij78; B) with chlorosulfonic acid. A carboxylate-terminated surfactant was synthesized by a substitution reaction of the sodium alkoxide form of B with sodium iodoacetate. XPS analysis of the modified PE samples showed that at short plasma treatment times of up to 5 s the structure of the immobilized surfactants is largely retained. When plasma treatment times longer than 30 s were applied, the PEO chains of the surfactants were degraded. The wettability of the modified PE samples was improved compared to the unmodified PE samples. The wettability of the modified samples did not change when they were stored in air at room temperature for at least 12 weeks.

The probability of pregnancy after embryo transfer is affected by the age of the patient, cause of infertility, number of embryos transferred and the average morphology score, as revealed by multiple logistic regression analysis.

Because the process of conception is affected by many variables, a multiple logistic regression analysis was performed to assess (i) the impact and relative weight of both patient and embryo variables and (ii) their possible effects on the probability of a vital pregnancy after embryo transfer. A statistical model was constructed predicting the probability of pregnancy after embryo transfer. The variables that contributed significantly to the predictive value of the model were the age of the patient, the cause of infertility, the number of embryos transferred and the average morphology score of the transferred embryos. Embryo variables appeared to have a significant but modest value in predicting the probability of pregnancy after embryo transfer. Other variables, such as the thickness of the endometrium, were found to have no prognostic value. Moreover, we found that their effect could be explained by the variables already included in the model.

Intraluminal Miller-Abbott tube stenting as treatment and prophylaxis of recurrent intestinal obstruction.

Chronic recurrent intestinal obstruction due to massive adhesions after abdominal surgery is a complication that is difficult to treat. The records were studied of 25 patients with acute intestinal obstruction due to massive adhesions. Since conservative measurements were unsuccessful, the patients were treated with internal intestinal splinting by means of a Miller-Abbott tube. These 25 patients underwent a total of 72 operations, 36 were performed for mechanical obstruction. Conservative treatment alone was effective during 25 admissions. The complaints of the patients lasted five years on an average. After lysis of adhesions the Miller-Abbott tube was introduced either via the nose, via a gastrostomy or via an enterostomy. The tube was left in situ for three weeks and then gradually withdrawn. There was no hospital mortality. There was one postoperative complication: a tube had to be removed under general anaesthesia. Long-term follow-up of the patients varied from 4.5 to 19 years with a mean of 11.3 years. One patient with recurrent intestinal obstruction due to adhesions, required surgical intervention after one year. A second patient with Peutz-Jeghers syndrome needed surgery because of an intestinal adenoma after six years. The mean symptom-free interval was 11.1 years in the cured patients.

Prevention of pulmonary embolism by caval interruption with a Greenfield vena cava filter: a report of four cases.

Interruption of the vena cava is the treatment of choice for patients with thrombosis of the femoral or iliac vein in whom anticoagulants have to be discontinued or cannot prevent recurrent pulmonary embolism. The technique of interruption of the vena cava is outlined and illustrated by the case history of four patients, treated with a Greenfield vena cava filter.

Antibodies to 'second colloid antigen.' A study on the prevalence in sporadic forms of congenital hypothyroidism.

Antibodies against the so called 'second colloid antigen' (CA2 antibodies) occurred in 51% of the mothers of hypothyroid children detected by screening for neonatal congenital hypothyroidism in Quebec (N = 49) and in The Netherlands (N = 26). In The Netherlands where corresponding neonatal serum was available, 31% (8 of 26) of the infants with congenital hypothyroidism were positive for antibodies against the second colloid antigen. When during follow-up, 3 to 5 years after diagnosis, the mothers and their children were investigated, 46% (7 of 15) of the mothers were positive for antibodies against the second colloid antigen, whereas 29% (4 of 14) of the hypothyroid children were also positive. Various control groups did not show more than a 12% positivity. This presence of thyroid-reactive antibodies in a proportion of the hypothyroid children 3 to 5 years after diagnosis is not compatible with a mere transplacental passage; it indicates that the antibodies must be produced by the mothers and by the children themselves. We conclude that a thyroid autoimmune response occurs in a considerable part of infants with congenital hypothyroidism and their mothers and that this immune response seems to persist in both of them for years.

Microbial flora and bile acid metabolism in patients with an ileal reservoir.

Bacterial flora of ileum effluent and bile acid metabolism were investigated in 11 patients 11-44 months after construction of a Kock's continent ileostomy. Bacteriologic investigation showed significantly more microorganisms per millilitre (p less than 0.01) and a more colon-like flora--that is, anaerobic microorganisms (p less than 0.001)--in ileum effluent of continent ileostomy patients than in ileum effluent of patients with a conventional ileostomy. The reabsorptive capacity of the reservoir mucosa was tested by direct introduction of a radioactively labelled conjugated bile acid, 23-75Se-25-homotaurocholic acid (SeHCAT), into the ileal pouch. After 4 h, 90% of the SeHCAT activity had been reabsorbed from the reservoir. Quantitative and differential analysis of bile acids in the ileum effluent showed unconjugated and predominantly primary (88%) bile acids, suggesting a minimal influence of bacterial flora on bile acid metabolism. Moreover, total bile acid loss appeared to be within normal limits.