"Multivariate analysis of the impact of sleep and working hours on medical errors: a MICE approach".

BACKGROUND: The main objective of this study was to describe the relationship between working conditions, sleep and psycho-affective variables and medical errors. METHODS: This was an observational, analytical and cross-sectional study in which 661 medical residents answered questionnaires about working conditions, sleep and psycho-affective variables. Actigraphic sleep parameters and peripheral temperature circadian rhythm were measured in a subgroup of 38 subjects. Bivariate and multivariate predictors of medical errors were assessed. RESULTS: Medical residents reported working 66.2 ± 21.9 weekly hours. The longest continuous shift was of 28.4 ± 10.9 h. They reported sleeping 6.1 ± 1.6 h per day, with a sleep debt of 94 ± 129 min in workdays. A high percentage of them reported symptoms related to psycho-affective disorders. The longest continuous shift duration (OR = 1.03 [95% CI, 1.00-1.05], p = 0.01), working more than six monthly on-call shifts (OR = 1.87 [95% CI, 1.16-3.02], p = 0.01) and sleeping less than six hours per working day (OR = 1.66 [95% CI, 1.10-2.51], p = 0.02) were independently associated with self-reported medical errors. The report of medical errors was associated with an increase in the percentage of diurnal sleep (2.2% [95% CI, 0.1-4.3] vs 14.5% [95% CI, 5.9-23.0]; p = 0.01) in the actigraphic recording. CONCLUSIONS: Medical residents have a high working hour load that affect their sleep opportunities, circadian rhythms and psycho-affective health, which are also related to the report of medical errors. These results highlight the importance of implementing multidimensional strategies to improve medical trainees' sleep and wellbeing, increasing in turn their own and patients' safety.

Evaluación respiratoria y manejo de pacientes con obesidad candidatos a procedimientos quirúrgicos y cirugía bariátrica / Respiratory evaluation and management of obese patients who are candidates for surgical procedures and bariatric surgery

En el seno de la Sección de Sueño, Oxigenoterapia y Asistencia Ventilatoria de la Asociación Argentina de Medicina Respiratoria, se planteó el desarrollo de sugerencias para la exploración respiratoria del paciente con obesidad y definiciones sobre el manejo perioperatorio en cirugía bariátrica y procedimientos quirúrgicos electivos (cirugía no bariátrica). Esta iniciativa se basó en la necesidad de contar con lineamientos adaptados a la realidad local y discutida por expertos que se desempeñan en la realidad coyuntural cotidiana de nuestro país. La agenda se inició en agosto de 2020 en un grupo de revisión de la bibliografía y redacción. Revisores de diferentes provincias argentinas efectuaron una extensa valoración de la evidencia. Luego, un comité editorial realizo una revisión crítica del documento. Finalmente, todo el grupo debatió las sugerencias que se exponen como puntos clave. Este documento exhorta a cirujanos y clínicos a trabajar junto a especialistas respiratorios en la evaluación del riesgo, definición de la aptitud operatoria y corrección de trastornos funcionales y apneas del sueño. La cirugía en individuos con obesidad y la cirugía bariátrica, son procedimientos a los que se arriba luego de una evaluación exhaustiva de la situación clínica y funcional. La tarea multidisciplinaria y el tratamiento de las anormalidades detectadas pueden disminuir los riesgos perioperatorios. Pacientes con obesidad que requieren cirugía electiva con anestesia general deben ser evaluados mediante pruebas objetivas para confirmar la presencia de apneas del sueño y estar adecuadamente tratados con CPAP.

Within the Sleep, Oxygen Therapy and Ventilatory Assistance Section of the Argentine Association of Respiratory Medicine, we de velopment of recommendations for the respiratory exploration of patients with obesity and definitions on perioperative management in bariatric surgery and elective surgical procedures (surgery non bariatric). This initiative was based on the need to have guidelines adapted to the local reality and discussed by experts who work in the daily conjunctural reality of our country. The schedule was started in August 2020 in a literature review group. Reviewers from different Argentine provinces carried out an extensive assessment of the evidence. Then, an editorial committee performed a critical review of the document. Finally, the whole group discussed the suggestions that are presented as key points. This document encourages surgeons and clinicians to work close to respiratory specialists in assessing risk, defining operative competence, and revise functional disorders and sleep apnea. Surgery in obese individuals and bariatric surgery are procedures that are reached after a detailed evaluation about clinical and functional situation. The multidisciplinary team and the treatment of detected abnormalities can reduce perioperative risks. Obese patients who require elective surgery with general anesthesia should be evaluated by objective tests to confirm the presence of sleep apnea and be adequately treated with CPAP.

Simplified sleep resistance test for daytime sleepiness detection.

OBJECTIVES: Excessive daytime sleepiness (EDS) is a highly prevalent symptom that increases the risk of traffic accidents and deteriorates the quality of life. The diagnosis of EDS is difficult because of the complex infrastructure that is required. The new test here proposed assesses the ability of a simple test of simplify the detection of daytime sleepiness compared with the OSLER test. MATERIAL AND METHODS: In the new test, during 20 minute subjects were asked to pass a finger by a groove in response to a light emitting diode, inside dark glasses, which was lit for 1s in every three, with headphones that reduce the ambient noise and was compared with the OSLER test on each subject in random order. RESULTS: The proposed method showed a sensitivity of 100% and a specificity of 61%, with a positive predictive value of 67% and negative predictive value of 100% when compared with the OSLER test. The value of area under the ROC curve was 0.81 (0.62-0.99), p=0.013. In a Bland-Altman plot, most of the latency times differences are in the 95% agreement interval (p=0.05). In addition, the confidence interval of the mean and most of the positive results are above the zero line. The Cohens Kappa coefficient obtained is 0.58 (95% CI 0.29-0.88). CONCLUSION: In this sample of patients, the proposed method detects EDS in a similar way as OSLER test and can be performed in different environments without requiring special infrastructure or expert personnel.

Recuperación de la frecuencia cardíaca post ejercicio en enfermos respiratorios crónicos

Las enfermedades respiratorias crónicas se asocian frecuentemente con disfunción autonómica cardíaca y esta se puede evaluar midiendo la recuperación de la frecuencia cardíaca (RFC) post ejercicio. Existen evidencias que la RFC calculada luego de un minuto de reposo después de la prueba de marcha de seis minutos (PM6M) puede predecir mortalidad y exacerbaciones agudas en pacientes con enfermedades respiratorias crónicas. El objetivo de este trabajo fue comparar la recuperación de la frecuencia cardíaca al finalizar una prueba del escalón de tres minutos de duración (PE3M) en enfermos respiratorios crónicos con la obtenida al finalizar la PM6M. La PE3M se realizó sin dificultad en un consultorio de reducidas dimensiones y todos los pacientes pudieron terminarlo. Aplicando el índice de correlación de Pearson se obtuvo como resultado 0,84 al comparar la RCF al minuto de detenerse en ambas pruebas lo que muestra una buena correlación entre ellas. En el gráfico de Bland Altman, se observa que los resultados están dentro de los límites de confianza mostrando concordancia a pesar de ser una muestra pequeña de pacientes. La PE3M se realiza con facilidad en un pequeño consultorio. Los resultados de la RCF después de esta prueba son comparables a los obtenidos al finalizar la PM6M.

Post-exercise Heart Rate Recovery in Patients with Chronic Respiratory Disease

Chronic respiratory diseases are frequently associated with cardiac autonomic dysfunction and this can be evaluated by measuring post-exercise heart rate recovery (HRR). There is evidence that the HRR calculated after one minute of rest following a Six-Minute Walk Test (6MWT) can predict mortality and acute exacerbations in patients with chronic respiratory diseases. The purpose of this study is to compare the heart rate recovery after finishing a Three-Minute Step Test (3MST) in chronic respiratory patients with that obtained after the 6MWT. The 3MST was performed without difficulty in a small doctor's office and all the patients were able to finish it. Applying the Pearson Correlation Index, the result was 0.84 when comparing the HRR one minute after stopping in both tests, showing a good correlation between them. In the Bland-Altman Plot, we can see that the results are within the confidence limits and show concordance despite being a small sample of patients. The 3MST is easily done in a small doctor's office. The results of the HRR after the 3MST are comparable to those obtained after finishing the 6MWT.

Indication of CPAP without a sleep study in patients with high pretest probability of obstructive sleep apnea.

OBJECTIVE: To evaluate the performance of clinical criteria (CC) for diagnosis and initiation of empirical treatment with continuous positive airway pressure (CPAP) in patients with suspected obstructive sleep apnea (OSA) compared with the treatment decision based on sleep studies (polysomnography or respiratory polygraphy), guidelines, and experience of participating physicians. METHODS: This was a simulated intention-to-treat study in a retrospective (G1) and prospective (G2) cohort. Four observers (two per group) called CC1 and CC2 reviewed the sleep questionnaires and indicated CPAP if the patients presented snoring, frequent apneas (≥ 3-4/week), body mass index (BMI) > 25 kg/m2, sleepiness (Epworth > 11), or tiredness (at least 3-4 times per week) and some comorbidity (hypertension, coronary/cerebrovascular event, diabetes). Ten independent observers formed two groups of five (FD1 and FD2) and were blinded to each other's opinion. These observers in FD1 and FD2 decided CPAP treatment based on guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) or guidelines of the American Academy of Sleep Medicine (AASM) and factored in their own opinion. Sensitivity (S), specificity (Sp), and positive/negative likelihood ratios (LR+/-) were calculated with the test method: CC1/2, and the reference method: majority decision of FD1/2. RESULTS: A total of 653 patients (264 women, 40%) were studied. Median age was 54 years, BMI 28 kg/m2, and apnea hypopnea index (AHI) 16.5 events/h. S ranged from 21 to 25% (p 0.60), Sp 96.1 to 97.6% (p 0.39), and LR+ of clinical criteria 6.4 to 8.9 (p 0.52). CONCLUSION: CPAP indication without a previous sleep study showed a low sensitivity (≅ 22%) but a specificity greater than 95% in patients with high pretest probability for OSA (snoring, report of frequent apneas, BMI > 25 kg/m2 and sleepiness or tiredness plus comorbidity).

Tratamiento con presión positiva de la Apnea Obstructiva del Sueño. Posición de la Asociación Argentina de Medicina Respiratoria / Treatment of Obstructive Sleep Apnea with Positive Pressure. Position of the Argentinian Association of Respiratory Medicine

La Sección de Sueño, Oxigenoterapia y Otros Tratamientos Crónicos Domiciliarios, de la Asociación Argentina de Medicina Respiratoria (AAMR) se planteó desarrollar en nuestro país un documento formal que exponga la base científica y costo económica de la cobertura del tratamiento del síndrome de apneas e hipopneas obstructivas durante el sueño (SAHOS). Esta iniciativa se basó en la necesidad de analizar la visión de expertos locales que se desempeñan en la realidad coyuntural cotidiana de nuestro país, para elaborar un documento informativo para miembros del equipo de salud. A su vez, exhorta a los diferentes actores del sistema a determinar pautas claras que sirvan de referencia para la generación de políticas públicas. La agenda se inició en septiembre de 2018 en un grupo de redacción. Luego, revisores de cinco provincias argentinas efectuaron una extensa valoración de la evidencia publicada. Para la edición final se realizó una reunión presencial de discusión y generación de consenso. Se plantearon como objetivos; actualizar la base científica que define al SAHOS como problema de salud de proporciones epidémicas con consecuencias demostrables en la salud, analizar los datos de costo-efectividad del tratamiento con CPAP para las formas moderadas a severas y leves con síntomas y unificar conceptos en relación con la calidad mínima necesaria en los tratamientos que se ofrecen. Finalmente, se analiza la situación en la Argentina sobre la base a datos publicados y se presenta una propuesta de mejora en tres niveles: social y económico, logístico-administrativo y clínico

The Sleep, Oxygen Therapy and Other Home Chronic Treatments Section of the Argentinian Association of Respiratory Medicine (AAMR, for its acronym in Spanish) proposed the development in our country of a formal document exposing the scientific and cost-economical foundation of the coverage for the treatment of obstructive sleep apnea and hypopnea syndrome (OSAHS). This initiative was based on the need to analyze the vision of local experts who work in the daily current reality of our country, in order to create an informative document for the members of the medical staff. In turn, it encourages the different members of the system to determine clear guidelines that could be used as reference for generating public policies. The agenda began in September, 2018 within a writing staff. Then, editors from five Argentinian provinces made a thorough assessment of published evidence. For the final edition, a face-to-face meeting was arranged to discuss and reach a consensus. The suggested objectives were: to update the scientific base that defines the OSAHS as a health problem of epidemic proportions with health consequences; to analyze cost-efficacy data of CPAP treatment for moderate to severe and mild-with-symptoms forms of the disease and to unify concepts in relation to the minimum necessary quality of treatments to be offered. Finally, the situation in Argentina is analyzed basing on published data, and a proposal is presented for improvement in three levels: social and economic, logistic-administrative and clinical.

Guías prácticas de diagnóstico y tratamiento del síndrome de apneas e hipopneas obstructivas del sueño: Actualización 2019: Sección Sueño, Oxigenoterapia y Tratamientos Crónicos Domiciliarios. Asociación Argentina de Medicina Respiratoria / Practical guides for diagnosis and treatment of obstructive sleep apneas and hypopneas syndrome: 2019 update. Sleep, Oxygen Therapy and Chronic Home Treatments Section. Argentine Association of Respiratory Medicine

Las apneas del sueño constituyen uno de los trastornos respiratorios crónicos de mayor relevancia en la población general, por su prevalencia, los efectos que produce en los pacientes que las padecen y su impacto en la salud pública. En el año 2013 se publicaron las primeras Guías Prácticas de diagnóstico y tratamiento del síndrome de apneas e hipopneas obstructivas del sueño de la AAMR. Desde entonces se ha generado un volumen significativo de evidencia científica sobre estos trastornos, lo que ha motivado la actualización de estas Guías Prácticas. Un grupo de trabajo, conformado por profesionales entrenados y con experiencia en trastornos respiratorios del sueño, revisó la bibliografía y actualizó los conceptos vertidos en las guías 2013. En su desarrollo se define el cuadro, los criterios diagnósticos y de gravedad, los factores de riesgo, las formas de presentación y sus consecuencias. Se detalla la metodología diagnóstica, sus distintas variables e indicaciones y los requisitos técnicos para su validación e interpretación. Por último se desarrollan las alternativas terapéuticas, así como también aspectos prácticos de su implementación. El objetivo central fue generar una herramienta de divulgación científica, que determine pautas claras que sirvan de referencia para la formación de profesionales, la atención de pacientes con esta enfermedad y la generación de políticas públicas.

Sleep apnea is one of the most relevant chronic respiratory disorders in the general population, given its prevalence, the effects it produces in patients and their impact on public health. In 2013, the first Practical Guidelines for diagnosis and treatment of obstructive sleep apnea syndrome of the AAMR were published. Since then, a significant volume of scientific evidence on these disorders has been generated, which has motivated the updating of these Practical Guidelines. A working group of trained professionals with experience in sleep breathing disorders reviewed the literature and updated the concepts included in the 2013 guidelines. Clinical aspects, diagnostic and severity criteria, risk factors, consequences and diagnostic strategy are addressed, as well as therapeutic alternatives and practical aspects of their implementation. The main objective was to generate practical guidelines that constitute a reference for the training of professionals, the care of patients with this disease and the generation of public policies.

CPAP indication based on clinical data and oximetry for patients with suspicion of obstructive sleep apnea: A multicenter trial.

BACKGROUND AND OBJECTIVE: The usefulness of pulse oximetry for the management of obstructive sleep apnea is controversial. The aim of this study was to assess the accuracy for indication of Continuous Positive Airway Pressure (CPAP) treatment in patients with suspected obstructive sleep apnea (OSA) based on clinical and oximetry data as compared to polysomnography (PSG). METHODS: This multicenter observational study involved seven sleep laboratories. Patients with suspicion of OSA who completed a standardized sleep questionnaire and a diagnostic PSG were enrolled. Eight observers logged on to a website independently and blindly. Seven observers only accessed the clinical data, curve and pulse oximetry results (Os-SO2-test method), while the eighth observer had full access to all indicators of PSG (O-PSG-reference method). Once observers assessed the information available on the website, they had to choose between three CPAP treatment options (yes/no/do not know) based on their knowledge and criteria. RESULTS: 411 subjects (228 men), median age 54 years, were available for evaluation. Os-SO2 had lower sensitivity (S), greater specificity (Sp) and positive likelihood ratio (PLR) to prescribe CPAP in patients more symptomatic (Epworth Sleepiness Scale-ESS > 10 or comorbidities) than those with fewer symptoms (ESS < 11 without comorbidities) (S 45-75% versus 45-91%, p 0.028); Sp 93.8-100% versus 68.5-96.6%, p 0.004; PLR > 10 versus 2.9-17, p<0.01). CONCLUSIONS: Due to its low false positive rate, a strategy based on pulse oximetry and clinical data was a consistent tool to indicate CPAP treatment in most symptomatic patients with a suspicion of OSA.

Recomendaciones sobre el uso de oxigenoterapia en situaciones especiales / Recommendations on the Use of Oxygen Therapy in Special Situations

La hipoxemia crónica severa se define por la presencia de una presión parcial de oxígeno arterial inferior a 60 mmHg. La oxigenoterapia, es decir el uso terapéutico del oxígeno, consiste en su administración a concentraciones mayores de las que se encuentran en el aire ambiente, con la intención de tratar o prevenir las manifestaciones de la hipoxia. Cuando se prescribe y se usa correctamente, ha demostrado que mejora la sobrevida en pacientes con EPOC e hipoxemia. Ha sido establecido que la oxigenoterapia a largo plazo representa el único tratamiento que mejora la evolución de pacientes con EPOC en etapa avanzada. En particular, dos estudios clave, el NOTT (Nocturnal Oxygen Therapy Trial) y el MRC (British Medical Research Council) hace más de 30 años han demostrado que la oxigenoterapia usada más de 15 horas por día, mejora la sobrevida de pacientes con EPOC severo más hipoxemia en reposo. A pesar de que este concepto se ha extendido por analogía a la insuficiencia respiratoria crónica originada por otras enfermedades respiratorias y no respiratorias, la eficacia de la oxigenoterapia continua no está demostrada claramente en otras entidades. Considerando que el 25% de las prescripciones de oxigenoterapia en nuestro medio no corresponden a pacientes con EPOC e hipoxemia, la Asociación Argentina de Medicina Respiratoria encomendó a un grupo de médicos neumonólogos argentinos la elaboración de la presente normativa, redactada a modo de guía sencilla, sobre el uso de la oxigeno-terapia en “situaciones especiales”, basada en nivel de evidencia por el sistema Grade.

The severe chronic hypoxemia is defined as an arterial partial oxygen pressure measuring less than 60 mmHg. Oxygen therapy is defined as the therapeutic use of oxygen; it consists in oxygen administration at higher concentrations than room air concentrations, to prevent or treat hypoxia. The right use of oxygen therapy has clearly shown to improve survival in hypoxemic chronic obstructive pulmonary disease (COPD) patients. It is well known that long-term oxygen therapy (LTOT) is the only treatment that has been proved to improve the late course of chronic obstructive pulmonary disease. Specially, two landmark studies, the Nocturnal Oxygen Therapy Trial (NOTT) and the British Medical Research Council (MRC) study conducted in the late 1970s have clearly demonstrated that LTOT (when used for more than 15hours/day) improves survival rates in patients with severe COPD associated with hypoxemia at rest. Although this concept has been extended by analogy to chronic respiratory failure caused by respiratory and non-respiratory diseases, continuous oxygen therapy has not been shown to be equally effective in other disorders. Because of 25% of patients who receive oxygen therapy do not have COPD with hypoxemia, the Argentine Association of Respiratory Medicine established a task force of pneumonologists to recommend guidelines about oxygen therapy in “special situations”, based on the level of evidence of the Grades System.

Development of a simple binary response questionnaire to identify airflow obstruction in a smoking population in Argentina.

The CODE questionnaire (COPD detection questionnaire), a simple, binary response scale (yes/no), screening questionnaire, was developed for the identification of patients with chronic obstructive pulmonary disease (COPD). We conducted a survey of 468 subjects with a smoking history in 10 public hospitals in Argentina. Patients with a previous diagnosis of COPD, asthma and other respiratory illness were excluded. Items that measured conceptual domains in terms of characteristics of symptoms, smoking history and demographics data were considered. 96 (20.5%) subjects had a diagnosis of COPD according to the 2010 Global Initiative for Chronic Obstructive Lung Disease strategy document. The variables selected for the final questionnaire were based on univariate and multivariate analyses and clinical criteria. Finally, we selected the presence or absence of six variables (age ≥50 years, smoking history ≥30 pack-years, male sex, chronic cough, chronic phlegm and dyspnoea). Of patients without any of these six variables (0 points), none had COPD. The ability of the CODE questionnaire to discriminate between subjects with and without COPD was good (the area under the receiver operating characteristic curve was 0.75). Higher scores were associated with a greater probability of COPD. The CODE questionnaire is a brief, accurate questionnaire that can identify smoking individuals likely to have COPD.

Effectiveness of home single-channel nasal pressure for sleep apnea diagnosis.

INTRODUCTION: Home single-channel nasal pressure (HNP) may be an alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis, but no cost studies have yet been carried out. Automatic scoring is simpler but generally less effective than manual scoring. OBJECTIVES: To determine the diagnostic efficacy and cost of both scorings (automatic and manual) compared with PSG, taking as a polysomnographic OSA diagnosis several apnea-hypopnea index (AHI) cutoff points. METHODS: We included suspected OSA patients in a multicenter study. They were randomized to home and hospital protocols. We constructed receiver operating characteristic (ROC) curves for both scorings. Diagnostic efficacy was explored for several HNP AHI cutoff points, and costs were calculated for equally effective alternatives. RESULTS: Of 787 randomized patients, 752 underwent HNP. Manual scoring produced better ROC curves than automatic for AHI < 15; similar curves were obtained for AHI ≥ 15. A valid HNP with manual scoring would determine the presence of OSA (or otherwise) in 90% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 74% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 61% of patients with a polysomnographic AHI ≥ 15 cutoff point. In the same way, a valid HNP with automatic scoring would determine the presence of OSA (or otherwise) in 73% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 64% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 57% of patients with a polysomnographic AHI ≥ 15 cutoff point. The costs of either HNP approaches were 40% to 70% lower than those of PSG at the same level of diagnostic efficacy. Manual HNP had the lowest cost for low polysomnographic AHI levels (≥ 5 and ≥ 10), and manual and automatic scorings had similar costs for higher polysomnographic cutoff points (AHI ≥ 15) of diagnosis. CONCLUSION: Home single-channel nasal pressure (HNP) is a cheaper alternative than polysomnography for obstructive sleep apnea diagnosis. HNP with manual scoring seems to have better diagnostic accuracy and a lower cost than automatic scoring for patients with low apnea-hypopnea index (AHI) levels, although automatic scoring has similar diagnostic accuracy and cost as manual scoring for intermediate and high AHI levels. Therefore, automatic scoring can be appropriately used, although diagnostic efficacy could improve if we carried out manual scoring on patients with AHI < 15. CLINICAL TRIALS INFORMATION: Clinicaltrials.gov identifier: NCT01347398.

Screening of obstructive sleep apnea with empirical mode decomposition of pulse oximetry.

Detection of desaturations on the pulse oximetry signal is of great importance for the diagnosis of sleep apneas. Using the counting of desaturations, an index can be built to help in the diagnosis of severe cases of obstructive sleep apnea-hypopnea syndrome. It is important to have automatic detection methods that allows the screening for this syndrome, reducing the need of the expensive polysomnography based studies. In this paper a novel recognition method based on the empirical mode decomposition of the pulse oximetry signal is proposed. The desaturations produce a very specific wave pattern that is extracted in the modes of the decomposition. Using this information, a detector based on properly selected thresholds and a set of simple rules is built. The oxygen desaturation index constructed from these detections produces a detector for obstructive sleep apnea-hypopnea syndrome with high sensitivity (0.838) and specificity (0.855) and yields better results than standard desaturation detection approaches.

Sleep disordered breathing and daytime sleepiness are associated with poor academic performance in teenagers. A study using the Pediatric Daytime Sleepiness Scale (PDSS).

STUDY OBJECTIVES: Inadequate sleep and sleep disordered breathing (SDB) can impair learning skills. Questionnaires used to evaluate sleepiness in adults are usually inadequate for adolescents. We conducted a study to evaluate the performance of a Spanish version of the Pediatric Daytime Sleepiness Scale (PDSS) and to assess the impact of sleepiness and SDB on academic performance. DESIGN: A cross-sectional survey of students from 7 schools in 4 cities of Argentina. MEASUREMENTS: A questionnaire with a Spanish version of the PDSS was used. Questions on the occurrence of snoring and witnessed apneas were answered by the parents. Mathematics and language grades were used as indicators of academic performance. PARTICIPANTS: The sample included 2,884 students (50% males; age: 13.3 +/- 1.5 years) RESULTS: Response rate was 85%; 678 cases were excluded due to missing data. Half the students slept <9 h per night on weekdays. The mean PDSS value was 15.74 +/- 5.93. Parental reporting of snoring occurred in 511 subjects (23%); snoring was occasional in 14% and frequent in 9%. Apneas were witnessed in 237 cases (11%), being frequent in 4% and occasional in 7%. Frequent snorers had higher mean PDSS scores than occasional or nonsnorers (18 +/- 5, 15.7 +/- 6 and 15.5 +/- 6, respectively; P < 0.001). Reported snoring or apneas and the PDSS were significant univariate predictors of failure and remained significant in multivariate logistic regression analysis after adjusting for age, sex, body mass index, specific school attended, and sleep habits. CONCLUSIONS: Insufficient hours of sleep were prevalent in this population. The Spanish version of the PDSS was a reliable tool in middle-school-aged children. Reports of snoring or witnessed apneas and daytime sleepiness as measured by PDSS were independent predictors of poor academic performance.

Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), NSC-624244) in patients with advanced cancer.

A Phase I clinical trial was performed on patients with solid tumors refractory to conventional therapy. Crotoxin was administered i.m. for 30 consecutive days at doses ranging from 0.03 to 0.22 mg/m(2). Patients entered the study after providing a written informed consent. Although 26 patients were entered only 23 were evaluated. Reversible, nonlimiting neuromuscular toxicity evidenced as diplopia because of pareses of the external ocular muscles was present in 13 patients. It started at doses of 0.18 mg/m(2) and lasted from 2 to 6 h. These episodes did not require dose adjustment and disappeared in 1-3 weeks of treatment. Three patients experienced palpebral ptosis, nystagmus (grade 2), and anxiety (grade 2-3) at the dose-limiting toxicity of 0.22 mg/m(2). Also at dose-limiting toxicity, 1 patient showed nystagmus (grade 2) and anxiety (grade 3) without evidence of palpebral ptosis. Transient increases (grades 1-3) in the levels of creatinine kinase, aspartate aminotransferase, and alanine transaminase attributed to crotoxin myotoxicity were observed but returned to normal by the last week of treatment. At 0.21 mg/m(2) there was a case of grade-3 anaphylactic reaction on day 31, which required treatment. Hypersensitivity was regarded as an adverse drug-related reaction, and the patient was removed from the protocol. Two patients at different doses (0.12 mg/m(2) and 0.22 mg/m(2)) had sialorrhea. Four patients had asymptomatic transient increase in blood pressure (up to 20 mm Hg) 12 h after the first injection, which lasted 24 h. No treatment was required and toxicity did not reappear. Six patients experienced slight eosinophilia during the first 2 weeks. The maximum tolerated dose was set at 0.21 mg/m(2). Objective measurable partial responses (>50% reduction of tumor mass) were noted in 2 patients treated at 0.21 mg/m(2) and 1 at 0.12 mg/m(2). One patient (at 0.21 mg/m(2)) presented a complete response on day 110. Crotoxin pharmacokinetics showed rapid absorption from the injection site to blood (t(1/2 A) = 5.2 +/- 0.6 min). Plasma concentration reached a peak (C(max) = 0.79 +/- 0.1 ng/ml) at tau(max) = 19 +/- 3 min. The half-life of the distribution (alpha) phase is 22 +/- 2 min. Starting at 1.5 h after injection, the decrease in plasma concentration becomes slower, reaching 14 +/- 3 pg/ml 24 h after injection. The profile is dominated by the elimination (beta) phase with a half-life of 5.2 +/- 0.6 h. Consequently, 24 h after the injection ( approximately 5 half-life) 97% of the product was eliminated. The area under plasma concentration versus time curve was 0.19 +/- 0.05 microg/min/ml. Assuming availability (F) approximately 1, the clearance is C(L) = 26.3 +/- 7 ml/min, and the apparent volume of distribution is V(d) = 12 +/- 3 liter/kg. The recommended dose for a Phase II study is 0.18 mg/m(2).