[Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study]. / Factores de riesgo de deterioro clínico en pacientes ingresados por COVID-19: estudio caso-control.

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. Setting: 13 acute care centers of the Osakidetza-Basque Health Service. Participants: Patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP >100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with < 150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.

A macroscopic clock model to solve the paradox of Schrödinger's cat.

We propose detecting the moment an atom emits a photon by means of a nearly classical macroscopic clock and discuss its viability. It is shown that what happens in such a measurement depends on the relation between the clock's accuracy and the width of the energy range available to the photon. Implications of the analysis for the long standing Schrödinger's cat problem are reported.

Impact of outdoor air pollution on severity and mortality in COVID-19 pneumonia.

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM10, PM2.5, O3, NO2, NO and NOX) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO2/FiO2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM10, NO2, NO and NOX, while higher exposure to NO2, NO and NOX was associated with lower SpO2/FiO2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO2/FiO2) in these patients were significantly related to exposure to air pollution.

Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study.

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. SETTING: 13 acute care centers of the Osakidetza-Basque Health Service. PARTICIPANTS: patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP > 100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with <150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.

[The role of the hospital pharmacist in the prevention, treatment and management of the side effects associated with antiretroviral treatment]. / Papel del farmacéutico de hospital en la prevención, identificación y manejo de los efectos adversos asociados al tratamiento antirretroviral.

At present, the side effects associated with antiretroviral treatment are the main reasons for discontinuation of this kind of therapy, both in clinical trials and in regular clinical practise. On the other hand, due to the change of direction that our profession has suffered in recent years, we face the need to establish a different relationship with the patient, achieving direct and effective Pharmaceutical Care within a framework of shared responsibility for therapeutic results. Pharmacist interventions should be aimed at improving the quality of life of patients, which can only be achieved with a multidisciplinary approach and individualised and adjusted to new patterns of toxicity of the drugs currently used. The pharmacist who does this work must know how to interpret these side effects, giving accurate information to the patient about both pharmacological and non-pharmacological treatment and correct pharmaceutical follow-up which clearly sets forth the criteria for referral to medical appointments. The aim of this paper is to establish baselines so that the hospital pharmacist can perform clearly and uniformly in the prevention, identification and management of major side effects: gastrointestinal, cardiovascular, dermatological, at the central nervous system and kidney level, associated with antiretroviral therapy.

Usefulness of the lymphocyte positional parameters in the Sysmex XN haematology analyser in lymphoproliferative disorders and mononucleosis syndrome.

INTRODUCTION: The lymphocyte positional parameters included in Sysmex XN have been suggested as useful means to differentiate lymphoproliferative disorders (LPD), mononucleosis syndrome (MNS) and other lymphocytoses. METHODS: We evaluated Sysmex XN analysers, which supply 6 lymphocyte positional parameters that can be measured in the WDF scattergram: LY-X, LY-Y, LY-Z, LY-WX, LY-WY and LY-WZ. RESULTS: We collected 301 samples from normal controls, polyclonal lymphocytosis, MNS and LPD. MNS and monoclonal expansion of T granular lymphocyte (T-GL) diagnostic groups accumulated higher numbers of significant differences in the mean values in comparison with the other groups. We propose a new algorithm that can differentiate T-GL cases from other diagnostic groups with an SE of 67.5%, an SP of 98.2%, a PPV of 87.1% and an NPV of 94.3%. Another algorithm showed its efficiency to differentiate MNS cases from other diagnostic groups with an SE of 63.6%, an SP of 97.5%, a PPV of 70.0% and an NPV of 96.7%. In 38.5% of all cases, the analyser did not generate any morphologic flag. Abnormal results in lymphocyte positional parameters were useful to detect 72.5% of these samples. CONCLUSION: The lymphocyte positional parameters provided by Sysmex XN analysers are useful to differentiate expansions of T-GLs from other LPD and to differentiate MNS cases from other diagnostic groups. In addition, these parameters are very useful for detecting changes in the lymphocytes that make it necessary to review blood smears in samples without morphological flagging.

Comparison of abnormal cell flagging of the hematology analyzers Sysmex XN and Sysmex XE-5000 in oncohematologic patients.

INTRODUCTION: Hematology analyzers should optimize flagging while minimizing false-negative results and unnecessary microscopic reviews. METHODS: We compared flagging performance of Sysmex XE-5000 and XN analyzers in oncohematologic patients. Differential counts were performed by Cellavision digital system (100 cells) and a hematologist (another 100 cells). RESULTS: First, we included 292 samples (86 with blasts): 28 acute lymphoblastic leukemia, 88 acute myeloid leukemia, 91 myelodysplastic syndromes, 45 chronic myeloproliferative neoplasms, and 40 chronic myelomonocytic leukemia. Sensitivity, specificity and efficiency to detect blasts were 59.3%, 88.3%, and 79.8% for XE-5000 analyzer and 70.9%, 91.3%, and 85.2% for the XN analyzer. Then, we included 111 lymphoid malignancies. In 55 CLL XE-5000 flagged for Abn Lympho/L_Blasts?, XN flagged for Abn Lympho?. In one-third of 19 samples with splenic marginal lymphoma, none of the analyzers flagged. In 5 Sézary syndrome cases, XE-5000 triggered the Abn Lympho/L_Blasts? flag while the flagging in XN was less consistent: Abn Lympho? Blasts? and Atypical Lympho?. In 5 hairy cell leukemias, both analyzers only flagged one sample. In 13 myelomas, XE-5000 generated Atypical Lympho? flag; XN triggered more variable flags. In other lymphoid malignancies, flags were variable. XN analyzer generates less samples with false basophilia. CONCLUSION: XN analyzer has improved blast detection in oncohematologic patients. Operators cannot rely on the blast flag alone but have to consider other flags and hemogram data. In lymphoproliferative disorders, XN analyzer yields less samples with pseudobasophilia. Both analyzers must improve flagging for hairy cell leukemia.

Integrated CMOS amplifier for ENG signal recording.

The development and in vivo test of a fully integrated differential CMOS amplifier, implemented with standard 0.7-microm CMOS technology (one poly, two metals, self aligned twin-well CMOS process) intended to record extracellular neural signals is described. In order to minimize the flicker noise generated by the CMOS circuitry, a chopper technique has been chosen. The fabricated amplifier has a gain of 74 dB, a bandwidth of 3 kHz, an input noise of 6.6 nV/(Hz)0.5, a power dissipation of 1.3 mW, and the active area is 2.7 mm2. An ac coupling has been used to adapt the electrode to the amplifier circuitry for the in vivo testing. Compound muscle action potentials, motor unit action potentials, and compound nerve action potentials have been recorded in acute experiments with rats, in order to validate the amplifier.

A comparative study of four coronal obturation materials in endodontic treatment.

The aim of this study was to compare, in vitro, the ability of temporary versus permanent materials to seal the access cavity. Eighty human maxillary single-canal teeth were prepared biomechanically and obturated with gutta-percha and an endodontic cement AH Plus, using the warm vertical compaction technique. All access cavities were sealed with 1 of 4 materials (Cavit, Fermit, Tetric, or Dyract). Microleakage was assessed by methylene blue dye penetration. The teeth were submitted to 100 thermocycles, with temperature varying from 0 degree to 55 degrees C. The greatest degree of leakage was observed with the temporary materials (Cavit and Fermit). There was a significant difference (p < 0.05) in leakage between all materials except between Dyract and Tetric. This suggests that it may be more prudent to use a permanent restorative material for provisional restorations to prevent inadequate canal sealing and the resulting risk of fluid penetration.

[Idiopathic spontaneous pneumothorax: treatment by small-caliber catheter aspiration compared to drainage through a chest tube]. / Neumotórax espontáneo idiopático: tratamiento basado en la aspiración con catéter fino frente a drenaje torácico.

BACKGROUND: Several options are available for treating patients with a first episode of primary spontaneous pneumothorax (ISP). The aim of this study was to compare the efficacy of two treatment alternatives: puncture-aspiration (PA) using a small caliber catheter, and pleural drainage through a chest tube (DCT). PATIENTS AND METHODS: We compared a current series of 91 patients treated with PA with a retrospective series of 216 patients treated with DCT. PA was performed by emergency room physicians and DCT was performed by chest surgeons. Patients were followed for a period of 24 months. RESULTS: The immediate efficacy of PA was superior to DCT (86.7% versus 76%, p < 0.05). The proportion of recurrences after each treatment was similar (23% and 17%, respectively, NS). Duration of hospital stay was shorter for PA-treated patients (24 h) than for DCT-treated patients (138 h) (p < 0.05). The efficacy of the two procedures 24 months later was similar (63.7% and 62.9%, respectively, NS), and the cost of PA was three times less than that of DCT. CONCLUSIONS: PA is as effective a treatment procedure as DCT. PA is simple enough for emergency room physicians to perform correctly. Inconvenience to the patient, cost to the health care system, and time of hospital stay are all significantly less with PA.

[Umbilical cord hematopoietic progenitor cells bank]. / Banco de células progenitoras hematopoyéticas de cordón umbilical.

Transplantation of hematopoietic progenitor cells (HPC) from bone marrow and mobilized peripheral blood is a standard therapy in malignant and non malignant diseases. The lack of suitable donors is an important limitation. The discovery that umbilical cord blood (CB) contains high numbers of HPC that can be used as an alternative source for allogeneic stem cell transplantation led ITMO to establish BANCEL, the first Argentine and Latinoamerican experience of its kind. The blood remaining in the umbilical cord and in the placenta was requested from women who were in the last quarter of pregnancy. An informed consent together with a medical record focused on family disease was completed. Out of 65 donations, 55 (85%) were collected and 51 (78%) were cryopreserved. Mean collected volume was 110 ml with 68% (75 ml) reduction and mean cryopreservation of 35 ml; ABO and Rh blood group systems were determined, HLA, class I, A and B loci, and class II, DR locus were typed by molecular biology methods using PCR-SSOP. Infectious disease screening was carried out for brucellosis, syphilis, Chagas, hepatitis B and C, HIV I and II, HTLV I and II, toxoplasmosis and cytomegalovirus. Two positive units for hepatitis B (anticore) and two positive units for Chagas were discarded. The quantity of total nucleated cells (TNC), CD34+ cells and the clonogenic capacity were determined twice at the collection and after the procedures of volume reduction previous to cryopreservation. A 5% reduction in both TNC and CD34 cells and a 10% in the colony forming units (CFU) were detected. A good correlation coefficient between TNC and CFU was obtained.

[Treatment of pulmonary hypertension]. / Tratamiento de la hipertensión pulmonar.

Pulmonary hypertension is a difficult-to-diagnose, poor-prognosis disease that may be primary or secondary to other conditions. It is characterized by pulmonary vasoconstriction, in situ thrombosis, and altered endothelial function, which clinically manifests with dyspnea and other disabling symptoms for the patient. Conventional treatment includes oral anticoagulants together with oxygen supplementation, diuretics, and digoxin --according to concurrent conditions-- as well as vasodilators, traditionally calcium antagonists. In recent years novel vasodilators have been developed for use in the treatment of pulmonary hypertension-prostaglandins (epoprostenol, iloprost), endothelin-1 receptor antagonists (bosentan), nitric oxide, and sildenafil, among other drugs under study. However, question marks remain on the management of this disease, and further studies are needed to find a truly effective therapeutic option.

[Simplification to lamivudine, zidovudine, and abacavir therapy: impact on adherence, clinical outcome, and economic issues]. / Simplificación con lamivudina, zidovudina y abacavir: repercusión sobre la adhrencia, resultados clínicos e impacto económico.

OBJECTIVES: To analyze the influence on adherence and clinical outcome of the replacement of a previous antiretroviral therapy to a simplified approach using zidovudine, lamivudine, and abacavir (Trizivir) and to assess its economic impact. METHODS: A retrospective study of 75 pretreated, HIV-infected adult patients who received Trizivir from May 2001 to December 2002. Adherence was assessed by dispensation records or medication counting, CD4 lymphocyte counts, and viral load before and six months after medication change was analyzed; finally, the cost of each therapy was assessed in order to calculate the economic impact of medication change. RESULTS: Mean adherence significantly increased a 2.5% after medication change; 16 more patients reached optimal adherence, with an NNT (number of patients requiring therapy change in order to obtain one more adherent) of 4.7. The number of patients with undetectable viral load remained almost similar, and mean CD4 cell counts stayed above 500 cells/mm3 in both periods of time. A great variability in incremental costs was seen, due to the varying costs of the previous treatments, and the influence of five intensification therapies using Trizivir. However, when only simplification regimens were analyzed such variability was reduced, and even became favorable in selected cases. CONCLUSIONS: Changing to a simplification therapy using Trizivir resulted in improved adherence, similar clinical outcomes, and a varying economic impact depending on previous antiretroviral therapy costs.

[Status of the structure, process and outcoms of pharmaceutical care to HIV patient in Spain. Origen study]. / Situación actual de la estructura, procesos y resultados de la Atención Farmacéutica al paciente VIH en España. Proyecto ORIGEN.

OBJECTIVES: To describe the structure, process and outcomes with which hospital pharmacist performs health care activity, teaching and research about Pharmaceutical Care (PC) in HIV patients in Spain. METHODS: Observational, cross-sectional and multicenter study carried out between November 2011-February 2012 in spanish hospitals. The inclusion criteria were: hospitals pharmacy services that dispensed antiretroviral medication to HIV patients. The questionnaire had 41 questions structured in 9 groups: hospital type and person conducting the survey, structure and resources, health care activities, interventions, communication with the rest of the multidisciplinary team, adherence, and quality records, management and pharmacoeconomy and teaching and research. Descriptive analysis was performed. To analyze the existence of statistically significant relationships, we applied fisher test, chi-square or logistic regression. RESULTS: 86 hospitals completed the survey. In 93%, PC consultation was not classified by pathologies. 27.9% provided continuing PC to all patients. Adherence was determined regularly or when pharmacist suspected poor adherence (57.5 %). 20% of hospital s teaching had a program that allowed a high level of training in PC to HIV patient. 52,3% of participating centers had published scientific articles related to HIV. CONCLUSIONS: Pharmaceutical care to HIV patients in Spain need to adapt to a new situation. For this, hospital pharmacists have to consider several issues such as chronicity, comorbidity, incorporation of new technologies and the stratification of patients in order to make it more efficient.

Objetivos: Describir la estructura, proceso y resultados con la que se lleva a cabo la actividad asistencial, docente e investigadora en torno a la Atención Farmacéutica (AF) al paciente VIH en los hospitales españoles. Material y métodos: Estudio observacional, transversal, pragmático y multicéntrico realizado entre Noviembre 2011-Febrero 2012. Participaron servicios de farmacia de hospitales españoles que dispensaran medicación antirretroviral para pacientes VIH. El cuestionario presentaba 41 preguntas estructuradas en 9 bloques: tipo de hospital y persona que realiza la encuesta, estructura y recursos disponibles, actividad asistencial, intervenciones, comunicación con el resto del equipo multidisciplinar, adherencia, registros y calidad, gestión y farmacoeconomía y docencia e investigación. Se realizó un análisis descriptivo y se aplicó la prueba de fisher, Chi cuadrado o regresión logística para analizar la existencia de relaciones estadísticamente significativas. Resultados: 86 hospitales cumplimentaron la encuesta. En el 93%, la consulta de AF era compartida con el resto de patologías. El 27,9% proporcionaba AF continuada a todos los pacientes. El 57,5% determinaban la adherencia periódicamente o en casos de sospecha de mala adhesión. El 20% de los hospitales docentes tenían un programa que permitía un alto nivel de formación en AF al paciente VIH. El 52,3% de los hospitales no habían publicado artículos científicos relacionados con el VIH. Conclusiones: La AF al paciente VIH+ en España debe adaptarse a un nuevo escenario donde se han de considerar aspectos como la cronicidad, la pluripatología, la incorporación de nuevas tecnologías y la necesidad de estratificación de los pacientes para hacerla más eficiente.

[Development and validation of a prediction model to identify HIV+ patients with drug-related problems. A prediction study]. / Desarrollo y validación de un modelo predictivo para la identificación de pacientes infectados por el VIH con problemas relacionados con los medicamentos. Estudio predictor.

OBJECTIVE: To develop and validate a prediction model for the detection of drug-related problems (DRP) in patients on antiretroviral treatment during their regular monitoring in Pharmaceutical Care Clinics before dispensing drugs. MEHOD: Open multicentre prospective study. HIV patients with and without DRP were included. Demographic, clinical and pharmacotherapy variables (related and unrelated to antiretroviral treatment) were included in the model design. To find prognostic factors for DRP, a binary logistic regression model was created after performing a univariate analysis that identified independent variables related to DRP these variables were introduced in the multivariate model for the final selection. Model validity was determined by the shrinkage method and the discriminatory power by Harrell's C-index. RESULTS: 733 patients were included. The variables "adherence", "prescription of drugs needing dosage adjustment", and "total number of drugs prescribed (apart from the antiretroviral treatment)" were independently related to the appearance of DRP. Probabilities predicted by the model, customising the coefficients using the uniform shrinkage method, showed a R(2)=0.962 for the construction sample and a R(2)=0.872 for the validation sample. The discriminatory capacity of the model was 0.816 for the construction sample and 0.779 for the validation sample. CONCLUSIONS: The developed and validated model enables detection of patients on antiretroviral treatment who are at a higher risk for experiencing a DRP. The prediction variables employed are commonly used in patient's pharmacotherapy record, allowing the model to be used in routine clinical practice.

Metal microelectromechanical oscillator exhibiting ultra-high water vapor resolution.

Water vapor sensing characterization of a metal resonator fabricated with an industrial 0.35 µm CMOS technology is reported. The resonator frequency is ∼13.2 MHz and exhibits a sensitivity magnitude of ∼3.5 kHz per %RH without requiring any additional hygroscopic coating layer. An on-chip integrated oscillator circuit enables an unprecedented resolution of 0.005 %RH.

Three-family supersymmetric standardlike models from intersecting brane worlds.

We construct the first three family N = 1 supersymmetric string model with standard model gauge group SU(3)(C) x SU(2)(L) x U(1)(Y) from an orientifold of type IIA theory on T(6)/(Z(2) x Z(2)) and D6-branes intersecting at angles. In addition to the minimal supersymmetric standard model particles, the model contains right-handed neutrinos, a chiral (but anomaly-free) set of exotic multiplets, and extra vectorlike multiplets. We discuss some phenomenological features of this model.

[Urachal cyst]. / Quiste de uraco.

OBJECTIVE: To describe an additional case of urachal cyst. METHODS/RESULTS: Herein we describe a patient with urachal cyst. The clinical and therapeutic aspects are discussed. CONCLUSION: The urachal cyst is an uncommon disease entity whose treatment is by surgery.

An integrated implantable electrical sacral root stimulator for bladder control.

Objectives. The goal of this work is to study and develop an electrical integrated system that allows the control of the basic functions (such as micturition, defecation, and erection) by sacral root stimulation in paraplegic patients. Materials and Methods. The system has been implemented using a commercially available Mietec CMOS technology. It is based on an external transceiver unit, which provides data and energy to the implant device through a bi-directional inductive link, and an implantable batteryless module that generates the needed current pulses, according to the orders received from the external unit. To test the electrode-tissue interface and system performance, an impedance measurement circuit has been included. Results. The three independent channel stimulators allow an exhaustive control of the waveform parameters (amplitude, pulse width, frequency) independent of the placement of the external coil respect to the internal device. Conclusion. The architecture of the new stimulator, applied over the sacral roots, can be used to control the voiding of the bladder. The system allows an independent distance programmable stimulation. The impedance measurement circuit implemented allows an easy and systematic performance test.