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1.
Can J Anaesth ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138798

ABSTRACT

PURPOSE: Intraoperative hypoglycemia is presumed to be rare, but generalizable multicentre incidence and risk factor data for adult patients are lacking. We used a multicentre registry to characterize adults with intraoperative hypoglycemia and hypothesized that intraoperative insulin administration would be associated with hypoglycemia. METHODS: We conducted a cross-sectional retrospective multicentre cohort study. We searched the Multicenter Perioperative Outcomes Group registry to identify adult patients with intraoperative hypoglycemia (glucose < 3.3 mmol·L-1 [< 60 mg·dL-1]) from 1 January 2015 to 31 December 2019. We evaluated characteristics of patients with intraoperative glucose measurements and with intraoperative hypoglycemia. RESULTS: Of 516,045 patients with intraoperative glucose measurements, 3,900 (0.76%) had intraoperative hypoglycemia. Diabetes mellitus and chronic kidney disease were more common in the cohort with intraoperative hypoglycemia. The odds of intraoperative hypoglycemia were higher for the youngest age category (18-30 yr) compared with the odds for every age category above 40 yr (odds ratio [OR], 1.57-3.18; P < 0.001), and were higher for underweight or normal weight patients compared with patients with obesity (OR, 1.48-2.53; P < 0.001). Parenteral nutrition was associated with lower odds of hypoglycemia (OR, 0.23; 95% confidence interval [CI], 0.11 to 0.47; P < 0.001). Intraoperative insulin use was not associated with hypoglycemia (OR, 0.996; 95% CI, 0.91 to 1.09; P = 0.93). CONCLUSION: In this large cross-sectional retrospective multicentre cohort study, intraoperative hypoglycemia was a rare event. Intraoperative insulin use was not associated with hypoglycemia.


RéSUMé: OBJECTIF: L'hypoglycémie peropératoire est présumée rare, mais il n'existe pas de données généralisables sur l'incidence multicentrique et les facteurs de risque chez la patientèle adulte. Nous avons utilisé un registre multicentrique pour caractériser les personnes adultes atteintes d'hypoglycémie peropératoire et émis l'hypothèse que l'administration peropératoire d'insuline serait associée à l'hypoglycémie. MéTHODE: Nous avons réalisé une étude de cohorte multicentrique rétrospective transversale. Nous avons effectué des recherches dans le registre du Multicenter Perioperative Outcomes Group afin d'identifier les patient·es adultes atteint·es d'hypoglycémie peropératoire (glucose < 3,3 mmol· L−1 [< 60 mg·dL−1]) du 1er janvier 2015 au 31 décembre 2019. Nous avons évalué les caractéristiques des patient·es présentant des mesures de glucose et une hypoglycémie peropératoires. RéSULTATS: Sur 516 045 patient·es ayant des mesures de glucose peropératoires, 3900 (0,76 %) ont présenté une hypoglycémie peropératoire. Le diabète sucré et l'insuffisance rénale chronique étaient plus fréquents dans la cohorte présentant une hypoglycémie peropératoire. Les risques d'hypoglycémie peropératoire étaient plus élevés pour la catégorie d'âge la plus jeune (18-30 ans) par rapport aux catégories d'âge au-dessus de 40 ans (rapport des cotes [RC], 1,57-3,18; P < 0,001), et étaient plus élevés chez les patient·es de poids insuffisant ou de poids normal par rapport aux patient·es obèses (RC, 1,48-2,53; P < 0,001). La nutrition parentérale était associée à une probabilité plus faible d'hypoglycémie (RC, 0,23; intervalle de confiance [IC] à 95 %, 0,11 à 0,47; P < 0,001). L'utilisation peropératoire d'insuline n'était pas associée à l'hypoglycémie (RC, 0,996; IC 95 %, 0,91 à 1,09; P = 0,93). CONCLUSION: Dans cette vaste étude de cohorte multicentrique rétrospective transversale, l'hypoglycémie peropératoire était un événement rare. L'utilisation peropératoire d'insuline n'était pas associée à l'hypoglycémie.

3.
Anesth Analg ; 132(4): 1075-1083, 2021 04 01.
Article in English | MEDLINE | ID: mdl-32639390

ABSTRACT

BACKGROUND: Intraoperative hypoglycemia can result in devastating neurologic injury if not promptly diagnosed and treated. Few studies have defined risk factors for intraoperative hypoglycemia. The authors sought to characterize children with intraoperative hypoglycemia and determine independent risk factors in a multicenter cohort. METHODS: This retrospective multicenter study included all patients <18 years undergoing an anesthetic from January 1, 2012, to December 31, 2016, at 12 institutions participating in the Multicenter Perioperative Outcomes Group (MPOG). The primary outcome was blood glucose <60 mg/dL (3.3 mmol/L). Data collected included patient characteristics, comorbidities, and intraoperative factors. A multivariable logistic regression model was used to identify independent predictors of intraoperative hypoglycemia. RESULTS: Blood glucose was measured in 26,142 of 394,231 (6.6%) cases. Of these, 1017 (3.9%) had a glucose <60 mg/dL (3.3 mmol/L). Independent predictors for intraoperative hypoglycemia identified were age <30 days (estimated adjusted odds ratio [AOR] vs ≥5 years 4.2; 95% confidence interval [CI], 3.4-5.3), age 30 days to <5 years (estimated AOR vs ≥5 years 2.7; 95% CI, 2.3-3.2), weight for age <5th percentile (estimated AOR, 1.6; 95% CI, 1.4-1.9), American Society of Anesthesiologists (ASA) status ≥III (estimated AOR, 1.3; 95% CI, 1.1-1.6), presence of a gastric or jejunal tube (estimated AOR, 1.3; 95% CI, 1.1-1.6), poor feeding (estimated AOR, 1.5; 95% CI, 1.2-1.7), and abdominal surgery (estimated AOR, 1.4; 95% CI, 1.1-1.7). Eighty percent of hypoglycemia occurred in children <5 years of age and in children <20 kg. CONCLUSIONS: Young age, weight for age <5th percentile, ASA status ≥III, having a gastric or jejunal tube, poor feeding, and abdominal surgery were risk factors for intraoperative hypoglycemia in children. Monitoring of blood glucose is recommended in these subsets of children.


Subject(s)
Blood Glucose/metabolism , Hypoglycemia/etiology , Surgical Procedures, Operative/adverse effects , Adolescent , Age Factors , Biomarkers/blood , Body Weight , Child , Child, Preschool , Databases, Factual , Enteral Nutrition/adverse effects , Female , Health Status , Humans , Hypoglycemia/blood , Hypoglycemia/diagnosis , Infant , Infant, Newborn , Intraoperative Period , Male , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , United States
4.
Clin Case Rep ; 8(12): 3066-3069, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33363881

ABSTRACT

Intrapericardial teratomas can exert mass effect on the cardiovascular and respiratory system. Adequate volume resuscitation and anticipation of cardiopulmonary collapse is paramount in the management of these patients in the operating room.

5.
Can J Anaesth ; 67(2): 225-234, 2020 02.
Article in English | MEDLINE | ID: mdl-31529370

ABSTRACT

PURPOSE: Intraoperative hypoglycemia can result in devastating neurologic injury if not promptly diagnosed and treated. Few studies have defined risk factors for intraoperative hypoglycemia. The authors sought to characterize children with intraoperative hypoglycemia and determine independent risk factors. METHODS: This retrospective observational single-institution study included all patients < 18 yr of age undergoing an anesthetic from January 1 2012 to December 31 2016. The primary outcome was blood glucose < 3.3 mmol·L-1 (60 mg·dl-1). Data collected included patient characteristics, comorbidities, and intraoperative factors. A multivariable logistic regression model was used to identify independent predictors of intraoperative hypoglycemia. RESULTS: Blood glucose was measured in 7,715 of 73,592 cases with 271 (3.5%) having a glucose < 3.3 mmol·L-1 (60 mg·dl-1). Young age, weight for age < 5th percentile, developmental delay, presence of a gastric or jejunal tube, and abdominal surgery were identified as independent predictors for intraoperative hypoglycemia. Eighty percent of hypoglycemia cases occurred in children < three years of age and in children < 15 kg. CONCLUSION: Young age, weight for age < 5th percentile, developmental delay, having a gastric or jejunal tube, and abdominal surgery were independent risk factors for intraoperative hypoglycemia in children. Frequent monitoring of blood glucose and judicious isotonic dextrose administration may be warranted in these children.


Subject(s)
Hypoglycemia , Intraoperative Complications , Blood Glucose , Child , Cohort Studies , Humans , Hypoglycemia/epidemiology , Hypoglycemia/etiology , Retrospective Studies , Risk Factors
6.
Pediatr Cardiol ; 40(8): 1633-1637, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31468061

ABSTRACT

We sought to assess acute hemodynamic changes after implementation of negative extrathoracic pressure (NEP) in spontaneously breathing ambulatory Fontan patients with symptomatic heart failure. We hypothesized that application of NEP would result in an acute decrease in pulmonary artery pressure. Ten patients with clinical evidence of Fontan failure underwent baseline hemodynamic catheterization while breathing spontaneously. Hemodynamic measurements were then repeated after 30 min of continuous NEP. After 30 min of continuous NEP, 4/10 patients had a decrease in their Fontan pressure by 2 mmHg and one patient had a decrease by 1 mmHg. There were three patients that had an increase in Fontan pressure by 2 mmHg. In 7/10 patients, indexed pulmonary vascular resistance decreased by an average of 31%. In symptomatic Fontan patients with a favorable hemodynamic response to NEP during catheterization, potential benefit of longer-term NEP to improve clinical status should be explored.


Subject(s)
Fontan Procedure/adverse effects , Respiration, Artificial/instrumentation , Ventilators, Negative-Pressure , Adolescent , Adult , Child , Female , Heart Failure/surgery , Hemodynamics/physiology , Humans , Male , Pilot Projects , Young Adult
7.
Pediatr Crit Care Med ; 20(10): 931-939, 2019 10.
Article in English | MEDLINE | ID: mdl-31169762

ABSTRACT

OBJECTIVES: The Pediatric Heart Network sponsored the multicenter Collaborative Learning Study that implemented a clinical practice guideline to facilitate early extubation in infants after repair of isolated coarctation of the aorta and tetralogy of Fallot. We sought to compare the anesthetic practice in the operating room and sedation-analgesia management in the ICU before and after the implementation of the guideline that resulted in early extubation. DESIGN: Secondary analysis of data from a multicenter study from January 2013 to April 2015. Predefined variables of anesthetic, sedative, and analgesia exposure were compared before and after guideline implementation. Propensity score weighted logistic regression analysis was used to determine the independent effect of intraoperative dexmedetomidine administration on early extubation. SETTING: Five children's hospitals. PATIENTS: A total of 240 study subjects who underwent repair of coarctation of the aorta or tetralogy of Fallot (119 preguideline implementation and 121 postguideline implementation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical practice guideline implementation was accompanied by a decrease in the median total intraoperative dose of opioids (49.7 vs 24.0 µg/kg of fentanyl equivalents, p < 0.001) and benzodiazepines (1.0 vs 0.4 mg/kg of midazolam equivalents, p < 0.001), but no change in median volatile anesthetic agent exposure (1.3 vs 1.5 minimum alveolar concentration hr, p = 0.25). Intraoperative dexmedetomidine administration was associated with early extubation (odds ratio 2.5, 95% CI, 1.02-5.99, p = 0.04) when adjusted for other covariates. In the ICU, more patients received dexmedetomidine (43% vs 75%), but concomitant benzodiazepine exposure decreased in both the frequency (66% vs 57%, p < 0.001) and cumulative median dose (0.5 vs 0.3 mg/kg of ME, p = 0.003) postguideline implementation. CONCLUSIONS: The implementation of an early extubation clinical practice guideline resulted in a reduction in the dose of opioids and benzodiazepines without a change in volatile anesthetic agent used in the operating room. Intraoperative dexmedetomidine administration was independently associated with early extubation. The total benzodiazepine exposure decreased in the early postoperative period.


Subject(s)
Airway Extubation/methods , Anesthetics/administration & dosage , Aortic Coarctation/surgery , Hypnotics and Sedatives/administration & dosage , Practice Guidelines as Topic , Tetralogy of Fallot/surgery , Analgesia/methods , Analgesics, Opioid/administration & dosage , Aortic Coarctation/drug therapy , Benzodiazepines/administration & dosage , Cardiac Surgical Procedures/methods , Dexmedetomidine/administration & dosage , Female , Humans , Infant , Infant, Newborn , Intensive Care Units, Pediatric , Male , Postoperative Care , Tetralogy of Fallot/drug therapy
8.
Catheter Cardiovasc Interv ; 88(6): 912-922, 2016 Nov 15.
Article in English | MEDLINE | ID: mdl-27801973

ABSTRACT

Current practice of sedation and anesthesia for patients undergoing pediatric congenital cardiac catheterization laboratory (PCCCL) procedures is known to vary among institutions, a multi-society expert panel with representatives from the Congenital Heart Disease Council of the Society for Cardiovascular Angiography and Interventions (SCAI), the Society for Pediatric Anesthesia (SPA) and the Congenital Cardiac Anesthesia Society (CCAS) was convened to evaluate the types of sedation and personnel necessary for procedures performed in the PCCCL. The goal of this panel was to provide practitioners and institutions performing these procedures with guidance consistent with national standards and to provide clinicians and institutions with consensus-based recommendations and the supporting references to encourage their application in quality improvement programs. Recommendations can neither encompass all clinical circumstances nor replace the judgment of individual clinicians in the management of each patient. The science of medicine is rooted in evidence, and the art of medicine is based on the application of this evidence to the individual patient. This expert consensus statement has adhered to these principles for optimal management of patients requiring sedation and anesthesia. What follows are recommendations for patient monitoring in the PCCCL regardless of whether minimal or no sedation is being used or general anesthesia is being provided by an anesthesiologist. © 2016 Wiley Periodicals Inc.


Subject(s)
Anesthesia, General/standards , Cardiac Catheterization , Conscious Sedation/standards , Consensus , Heart Defects, Congenital/surgery , Practice Guidelines as Topic , Angiography , Child , Heart Defects, Congenital/diagnosis , Humans
9.
Anesth Analg ; 123(5): 1201-1209, 2016 11.
Article in English | MEDLINE | ID: mdl-27749349

ABSTRACT

Current practice of sedation and anesthesia for patients undergoing pediatric and congenital cardiac catheterization laboratory (PCCCL) procedures is known to vary among institutions, a multi-society expert panel with representatives from the Congenital Heart Disease Council of the Society for Cardiovascular Angiography and Interventions, the Society for Pediatric Anesthesia and the Congenital Cardiac Anesthesia Society was convened to evaluate the types of sedation and personnel necessary for procedures performed in the PCCCL. The goal of this panel was to provide practitioners and institutions performing these procedures with guidance consistent with national standards and to provide clinicians and institutions with consensus-based recommendations and the supporting references to encourage their application in quality improvement programs. Recommendations can neither encompass all clinical circumstances nor replace the judgment of individual clinicians in the management of each patient. The science of medicine is rooted in evidence, and the art of medicine is based on the application of this evidence to the individual patient. This expert consensus statement has adhered to these principles for optimal management of patients requiring sedation and anesthesia. What follows are recommendations for patient monitoring in the PCCCL regardless of whether minimal or no sedation is being used or general anesthesia is being provided by an anesthesiologist.


Subject(s)
Anesthesia, General/standards , Cardiac Catheterization/standards , Conscious Sedation/standards , Heart Defects, Congenital/therapy , Practice Guidelines as Topic/standards , Societies, Medical/standards , Anesthesia, General/methods , Anesthesiology/methods , Anesthesiology/standards , Child , Conscious Sedation/methods , Consensus , Heart Defects, Congenital/diagnosis , Humans
10.
Ann Thorac Surg ; 96(3): 910-6, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23866807

ABSTRACT

BACKGROUND: Blood product transfusion during cardiopulmonary bypass has been demonstrated to be associated with increased morbidity and mortality in adult cardiac surgery populations. The aim of this study was to characterize the risk-adjusted occurrence of postoperative complications and mortality in relation to intraoperative blood product transfusion in our pediatric cardiac surgery population. METHODS: A retrospective review was performed on 1,631 consecutive cardiopulmonary bypass cases to determine the effects of intraoperative blood product transfusion on selected outcomes. After adjusting for patient and operative risk factors, multivariate analysis was performed to determine the association between blood product transfusion and postoperative complications. Cox proportional hazards model was used to examine the relationship of packed red blood cell transfusion to hospital length of stay. RESULTS: Red blood cell and fresh frozen plasma transfusion was associated with pulmonary complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.05 to 2.28; p=0.03). Red blood cell transfusion also correlated with prolonged hospital stay (p<0.01). Cryoprecipate transfusion was associated with postoperative pulmonary complications (adjusted odds ratio, 1.79; 95% confidence interval, 1.13 to 2.55; p=0.01), but decreased incidence of 30-day mortality (adjusted odds ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.02). Platelet transfusion was associated with decreased 30-day mortality (adjusted odds ratio, 0.51; 95% confidence interval, 0.28 to 0.93; p=0.04), but not overall mortality. CONCLUSIONS: Blood product transfusion was associated with an increased incidence of postoperative pulmonary complications and prolonged hospital length of stay, but not overall mortality. These findings suggest that minimizing blood product transfusion would be beneficial in the pediatric cardiopulmonary bypass surgery patient population.


Subject(s)
Cardiopulmonary Bypass/methods , Erythrocyte Transfusion/adverse effects , Hospital Mortality/trends , Postoperative Complications/mortality , Adolescent , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Cardiopulmonary Bypass/adverse effects , Cause of Death , Child , Child, Preschool , Cohort Studies , Confidence Intervals , Erythrocyte Transfusion/methods , Female , Follow-Up Studies , Humans , Incidence , Infant , Intraoperative Care/methods , Male , Multivariate Analysis , Odds Ratio , Postoperative Complications/physiopathology , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Treatment Outcome
11.
Paediatr Anaesth ; 21(8): 880-6, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21306475

ABSTRACT

UNLABELLED: Acute kidney injury (AKI) is a serious complication that occurs commonly following cardiopulmonary bypass (CPB) in infants and children. Underlying risk factors for AKI remain unclear, given changes in CPB practices during recent years. This retrospective, case-control study examined the relationships between patient, perioperative factors, AKI, and kidney failure in children who underwent CPB. METHODS: Cohorts of children with and without AKI were identified from the cardiac perfusion and nephrology consult databases. Demographic, perioperative, and postoperative outcome data were extracted from the databases and from medical records. Children were stratified into groups based on the Acute Dialysis Quality Initiative's RIFLE definitions for acute kidney risk or injury (AKI-RI) and kidney failure. RESULTS: The study groups included 308 controls (no AKI-RI or failure), 161 with AKI-RI, and 89 with failure. Young age, preoperative need for mechanical ventilation, milrinone, or gentamicin; intraoperative use of milrinone and furosemide; durations of CPB and anesthesia; multiple cross-clamp and transfusion of blood products were significantly associated with AKI or failure. Young age, perioperative use of milrinone, multiple cross-clamps, extracorporeal membrane oxygenation, cardiac failure, neurological complications, sepsis, and failure significantly increased the odds of mortality. CONCLUSION: This study identified multiple perioperative risk factors for AKI-RI, failure, and mortality in children undergoing CPB. In addition to commonly known risk factors, perioperative use of milrinone, particularly in young infants, and furosemide were independently predictive of poor renal outcomes in this sample. Findings suggest a need for the development of protocols aimed at renal protection in specific at risk patients.


Subject(s)
Acute Kidney Injury/etiology , Cardiopulmonary Bypass/adverse effects , Acute Kidney Injury/epidemiology , Age Factors , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Databases, Factual , Electronic Health Records , Female , Heart Defects, Congenital/surgery , Hemofiltration , Humans , Infant , Infant, Newborn , Male , Medical Records , Perioperative Period , Postoperative Complications/epidemiology , Renal Dialysis , Retrospective Studies , Risk , Treatment Outcome
12.
Anesthesiology ; 98(3): 628-32, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12606905

ABSTRACT

BACKGROUND: Otherwise healthy children who present for elective surgery with an upper respiratory infection (URI) may be at risk for perioperative respiratory complications. This risk may be increased in children with congenital heart disease who undergo cardiac surgery while harboring a URI because of their compromised cardiopulmonary status. Therefore, this study was designed to determine the incidence of peri- and postoperative complications in children undergoing cardiac surgery while harboring a URI. METHODS: The study population consisted of 713 children scheduled to undergo cardiac surgery. Of these, 96 had symptoms of URI, and 617 were asymptomatic. Children were followed prospectively from induction of anesthesia to discharge from the hospital to determine the incidence of postoperative respiratory, cardiovascular, neurologic, and surgical adverse events. Duration of postoperative ventilation, time in the intensive care unit (ICU), and length of hospital stay were also recorded. RESULTS: Children with URIs had a significantly higher incidence of respiratory and multiple postoperative complications than children with no URIs (29.2 vs 17.3% and 25 vs 10.3%, respectively; P< 0.01) and a higher incidence of postoperative bacterial infections (5.2 vs 1.0%; P= 0.01). Furthermore, logistic regression indicated that the presence of a URI was an independent risk factor for multiple postoperative complications and postoperative infections in children undergoing open heart surgery. Children with URIs also stayed longer in the intensive care unit than children with no URIs (75.9 +/- 89.8 h vs 57.7 +/- 63.8, respectively; P< 0.01). However, the overall length of hospital stay was not significantly different (8.4 vs 7.8 days, URI vs non-URI groups; P> 0.05). CONCLUSIONS: The presence of a URI was predictive of postoperative infection and multiple complications in children presenting for cardiac surgery. Despite this, the presence of a URI does not appear to affect the patient's overall length of hospital stay nor the development of long-term sequelae.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Postoperative Complications/etiology , Respiratory Tract Infections/complications , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Length of Stay , Logistic Models , Male , Risk Factors
13.
Crit Care Med ; 30(12): 2649-54, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12483054

ABSTRACT

OBJECTIVE: To determine the effects of adding 5% albumin to the cardiopulmonary bypass prime on perioperative fluid status and fluid management in young children. DESIGN: Prospective randomized study. SETTING: Single university hospital. PATIENTS: Pediatric patients of <14 kg undergoing cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: Patients received a 5% albumin prime or a crystalloid prime. Perioperative fluid intake, output, and daily weights were recorded. Serial hematocrits, colloid osmotic pressures, and serum albumins were measured. Outcomes and complications were documented. MEASUREMENTS AND MAIN RESULTS: There were 86 patients aged 3 days to 4 yrs; 44 patients had an albumin prime and 42 had a crystalloid prime. Patients in the albumin group had a net negative fluid balance at the end of cardiopulmonary bypass compared with a net positive fluid balance in the crystalloid group. Patients in the albumin group had significantly higher serum albumins and colloid osmotic pressures and gained less weight postoperatively. However, their hematocrits were lower, and more patients in the albumin group received packed red blood cells. By 24 hrs postoperatively, there were no differences in colloid osmotic pressures and hematocrits between groups, and by the fourth postoperative day, there was no difference in weight gain. No differences were found in length of mechanical ventilation, intensive care unit or hospital stay, complications, or mortality. CONCLUSIONS: Albumin in the prime may attenuate the extravasation of fluid out of the vascular space, but it may be associated with an increased transfusion rate. The risk/benefit ratio for this intervention warrants further study.


Subject(s)
Albumins/therapeutic use , Cardiopulmonary Bypass/methods , Colloids/therapeutic use , Analysis of Variance , Child, Preschool , Female , Hematocrit , Humans , Infant , Infant, Newborn , Male , Osmotic Pressure , Prospective Studies , Statistics, Nonparametric , Treatment Outcome , Weight Gain
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