Mesenchymal Stem Cell Extracellular Vesicles from TissueMimetic System Enhance Epidermal Regeneration via Formation of Migratory Cell Sheets

BACKGROUND@#The secretome of adipose-derived mesenchymal stem cells (ASCs) offers a unique approach to understanding and treating wounds, including the critical process of epidermal regeneration orchestrated by keratinocytes.However, 2D culture techniques drastically alter the secretory dynamics of ASCs, which has led to ambiguity in understanding which secreted compounds (e.g., growth factors, exosomes, reactive oxygen species) may be driving epithelialization. @*METHODS@#A novel tissue-mimetic 3D hydrogel system was utilized to enhance the retainment of a more regenerative ASC phenotype and highlight the functional secretome differences between 2D and 3D. Subsequently, the ASC-secretome was stratified by molecular weight and the presence/absence of extracellular vesicles (EVs). The ASC-secretome fractions were then evaluated to assess for the capacity to augment specific keratinocyte activities. @*RESULTS@#Culture of ASCs within the tissue-mimetic system enhanced protein secretion * 50%, exclusively coming from the [ 100 kDa fraction. The ASC-secretome ability to modulate epithelialization functions, including migration, proliferation, differentiation, and morphology, resided within the ‘‘[ 100 kDa’’ fraction, with the 3D ASC-secretome providing the greatest improvement. 3D ASC EV secretion was enhanced two-fold and exhibited dose-dependent effects on epidermal regeneration. Notably, ASC-EVs induced morphological changes in keratinocytes reminiscent of native regeneration, including formation of stratified cell sheets. However, only 3D-EVs promoted collective cell sheet migration and an epithelial-to-mesenchymal-like transition in keratinocytes, whereas 2D-EVs contained an anti-migratory stimulus. @*CONCLUSION@#This study demonstrates how critical the culture environment is on influencing ASC-secretome regenerative capabilities. Additionally, the critical role of EVs in modulating epidermal regeneration is revealed and their translatability for future clinical therapies is discussed.

Clinical utilization of four-factor prothrombin complex concentrate: a retrospective single center study

Objective@#Four-factor prothrombin complex concentrate (4F-PCC) was approved by the US Food and Drug Administration in 2013 for management of severely bleeding patients on warfarin therapy. We describe use of 4F-PCC at a large, suburban academic center. @*Methods@#We retrospectively reviewed all patients receiving 4F-PCC from its introduction through 2016 at a large level 1 trauma center. Clinical and demographic data were obtained, including indications for anticoagulation and antiplatelet agents, comorbidities, concomitant medications, etiology and site of bleeding, as well as disposition, length of stay, mortality, and thrombotic events. @*Results@#One hundred eighty-four patients received 4F-PCC. Mean age was 72 years; 40.8% were female. Indications for 4F-PCC administration included: active bleeding (74%), reversal prior to a procedure (14%), and elevated international normalized ratio (12%). Warfarin was the most common concomitant medication (71.1%). Most patients were receiving anticoagulation for atrial fibrillation (63%). Concomitant treatments for bleeding included vitamin K (58.2%), packed red blood cells (50%), fresh frozen plasma (38%), and platelets (26.1%), amongst others. Median length of hospital stay was 8.4 days. Nine patients (4.9%) developed thrombosis within 90 days of 4F-PCC. Mortality was 24.5%, with notably higher rates amongst those who received 4F-PCC for off-label indications (19.1% on-label mortality vs. 37.7% off-label mortality on chi-square analysis, P=0.01). @*Conclusion@#This study demonstrates that 4F-PCC is being utilized for indications other than the reversal of warfarin-induced coagulopathy. Further investigation is warranted to determine the efficacy and safety of 4F-PCC for these potential indications.

Clinical utilization of four-factor prothrombin complex concentrate: a retrospective single center study

Objective@#Four-factor prothrombin complex concentrate (4F-PCC) was approved by the US Food and Drug Administration in 2013 for management of severely bleeding patients on warfarin therapy. We describe use of 4F-PCC at a large, suburban academic center. @*Methods@#We retrospectively reviewed all patients receiving 4F-PCC from its introduction through 2016 at a large level 1 trauma center. Clinical and demographic data were obtained, including indications for anticoagulation and antiplatelet agents, comorbidities, concomitant medications, etiology and site of bleeding, as well as disposition, length of stay, mortality, and thrombotic events. @*Results@#One hundred eighty-four patients received 4F-PCC. Mean age was 72 years; 40.8% were female. Indications for 4F-PCC administration included: active bleeding (74%), reversal prior to a procedure (14%), and elevated international normalized ratio (12%). Warfarin was the most common concomitant medication (71.1%). Most patients were receiving anticoagulation for atrial fibrillation (63%). Concomitant treatments for bleeding included vitamin K (58.2%), packed red blood cells (50%), fresh frozen plasma (38%), and platelets (26.1%), amongst others. Median length of hospital stay was 8.4 days. Nine patients (4.9%) developed thrombosis within 90 days of 4F-PCC. Mortality was 24.5%, with notably higher rates amongst those who received 4F-PCC for off-label indications (19.1% on-label mortality vs. 37.7% off-label mortality on chi-square analysis, P=0.01). @*Conclusion@#This study demonstrates that 4F-PCC is being utilized for indications other than the reversal of warfarin-induced coagulopathy. Further investigation is warranted to determine the efficacy and safety of 4F-PCC for these potential indications.

School-based yoga intervention increases adolescent resilience: a pilot trial

Background: Youth often experience stressors leading to negative long-term outcomes. Enhancing social-emotional attributes is important to foster resiliency to face these challenges. Yoga may enhance social-emotional resiliency among youth. However, research replicating such results in school-settings is limited. This research details an investigation of the effects of the Kripalu Yoga in the Schools (KYIS) intervention integrated into a physical education class among a racially/ethnically diverse student population. Method: Middle school sixth grade students (n = 23 students; 52% female; mean age = 12.1 years) were either enrolled in physical education class that included KYIS (n = 9), or were enrolled in art and music (control condition; n = 14). To evaluate effects on student characteristics, self-report questionnaires of social-emotional competence and problem behaviour were administered pre- and post-delivery of the curriculum. Results: Students receiving the intervention increased in social-emotional competence over time relative to the control condition. Although promising, results should be interpreted with caution, as students who received the yoga intervention scored significantly lower on social-emotional competence than students in the control group at pre-intervention measurement time point. Conclusions: Yoga may improve social-emotional competence among youth and future research should explore the utility of yoga curricula in school settings

Emergency medicine physicians infrequently perform pediatric critical procedures: a national perspective

Objective@#To our knowledge, this is the first comprehensive study using a nationally representative database to estimate the frequency of critical procedures (endotracheal tube intubation [ETI], cardiopulmonary resuscitation [CPR], and central line insertion [CLI]) in children and adults. @*Methods@#The study was based on the secondary analysis of the 2010-2014 National Hospital Ambulatory Medical Care Survey. We included adult and pediatric patients undergoing critical procedures in the emergency department. We extracted demographic and clinical information, including the performance of critical procedures. For frequent procedures (≥1 per year), we estimated the annual number of critical procedures per emergency physician (EP) by dividing the total number of annual critical procedures by the total number of EPs (estimated at 40,000). For infrequent procedures, we calculated the average interval between procedures. We summarized the data with descriptive statistics and 95% confidence intervals (CIs). @*Results@#There were an estimated 668 million total emergency department visits (24% pediatric). On average, a single EP performed 8.6 (95% CI, 5.5 to 11.7) CLIs, 3.7 (95% CI, 2.4 to 5.0) CPRs, and 6.3 (95% CI, 5.3 to 7.4) ETIs per year in adults. In comparison, a single EP performed one pediatric CLI, CPR, and ETI every 3.2 (95% CI, 1.9 to 9.8), 5.2 (95% CI, 2.8 to 33.5), and 2.8 (95% CI, 1.6 to 8.9) years, respectively. @*Conclusion@#Our nationwide findings confirm those of previous smaller studies that critical procedures are significantly fewer in children than adults. We suggest that methods to retain skills in pediatric critical procedures should be developed for general EPs to ensure that they deliver the highest level of care across the entire age spectrum.

Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies

Objective: To analyze the efficacy and safety of paliperidone palmitate 3-monthly (PP3M) in Latin American patients with schizophrenia vs. rest-of-world (ROW). Methods: We analyzed data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on PP1M/PP3M (open-label [OL] phase). Patients were randomized to PP3M or PP1M (noninferiority study A) and PP3M or placebo (study B) in DB phase. The subgroup analysis included Latin American (Argentina, Brazil, Colombia, Mexico) patients. Primary efficacy endpoints were relapse-free rates (study A) and time-to-relapse (study B). Results: In study A, 63/71 (88.7%) and in study B 38/43 (88.4%) Latin American patients completed the DB phase. In study A, relapse-free percentage was similar in Latin America (PP3M: 97%, PP1M: 100%) and ROW (PP3M: 91%, PP1M: 89%). In study B, median time-to-relapse was not estimable in the Latin American subgroup for either placebo or PP3M groups, nor for the ROW PP3M group; the median time-to-relapse in the ROW placebo group was 395 days. Caregiver burden improved in patients switching from oral antipsychotics (OL baseline) to PP3M/PP1M in DB phase (Involvement Evaluation Questionnaire score mean ± SD change, -9.4±15.16; p < 0.001). Treatment emergent adverse events with PP3M during DB phase were similar in Latin America (study A: 24/34 [70.6%]; study B: 15/21 [71.4%]) and ROW (study A: 318/470 [67.7%]; study B: 84/139 [60.4%]) subgroups. Conclusion: PP3M was efficacious and showed no new safety concerns in patients with schizophrenia from Latin America, corroborating ROW findings. Clinical trial registration: NCT01515423, NCT01529515

Nutritional intake of children aged between one and three years in Metn nurseries: state and recommendations

Early childhood is the perfect time to teach the child good eating habits, especially in nurseries through their educators and the offered menu. These nurseries should therefore ensure that their menus are varied and balanced. This study aims to analyze nutritionally the menus offered to children, from one to three years old in Lebanese nurseries located in Metn. For this purpose, a survey was made including a demographic standardized questionnaire addressed to nurseries heads, with another nutritional standardized questionnaire addressed to nurseries teachers and a checklist also standardized to locate the current nutritional status of nurseries. Among fifty-three visited nurseries, a sampling of thirty menus acquired was used for this analysis and the results demonstrated the lack of conformity between the offered nutrient intakes and the recommended American corresponding reference. This non-compliance is due to an excess of 28.2Percent of recommended energy intake, 23.6Percent and 51Percent respectively of carbohydrates and proteins, whereas only fat intake appears consistent. The iron intake exceeded recommendations by 39.3Percent, while zinc exceeded by 65Percent; only vitamin A intake was 46.2Percent below the recommended intake. Nurseries educators' nutritional knowledge was found to be insufficient. Accordingly, these results indicate the need to improve the quality and quantity of food provided to children in nurseries and the necessity for nurseries educators training and education in early childhood nutrition

Protocol and Rationale: A 24-week Double-blind, Randomized, Placebo Controlled Trial of the Efficacy of Adjunctive Garcinia mangostana Linn. (Mangosteen) Pericarp for Schizophrenia

OBJECTIVE: Garcinia mangostana Linn., commonly known as mangosteen, is a tropical fruit with a thick pericarp rind containing bioactive compounds that may be beneficial as an adjunctive treatment for schizophrenia. The biological underpinnings of schizophrenia are believed to involve altered neurotransmission, inflammation, redox systems, mitochondrial dysfunction, and neurogenesis. Mangosteen pericarp contains xanthones which may target these biological pathways and improve symptoms; this is supported by preclinical evidence. Here we outline the protocol for a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp (1,000 mg/day), compared to placebo, in the treatment of schizophrenia. METHODS: We aim to recruit 150 participants across two sites (Geelong and Brisbane). Participants diagnosed with schizophrenia or schizoaffective disorder will be randomized to receive 24 weeks of either adjunctive 1,000 mg/day of mangosteen pericarp or matched placebo, in addition to their usual treatment. The primary outcome measure is mean change in the Positive and Negative Symptom Scale (total score) over the 24 weeks. Secondary outcomes include positive and negative symptoms, general psychopathology, clinical global severity and improvement, depressive symptoms, life satisfaction, functioning, participants reported overall improvement, substance use, cognition, safety and biological data. A 4-week post treatment interview at week 28 will explore post-discontinuations effects. RESULTS: Ethical and governance approvals were gained and the trial commenced. CONCLUSION: A positive finding in this study has the potential to provide a new adjunctive treatment option for people with schizophrenia and schizoaffective disorder. It may also lead to a greater understanding of the pathophysiology of the disorder.

Updates in emergency department laceration management

Lacerations are a common reason for patients to seek medical attention, and are often acutely managed in the emergency department. Recent studies pertaining to closure techniques, sedation and analgesia, advances in wound care, and various other topics have been published, which may enhance our understanding of this injury and improve our management practices. This article will review pertinent studies published in the past few years relevant to laceration management. Understanding the current literature and appreciating which areas warrant further investigation will help us optimize outcomes for patients who sustain laceration injuries.

Impact of Elosulfase Alfa on Pain in Patients with Morquio A Syndrome over 52 Weeks: MOR-008: A Randomized, Double-Blind, Pilot Study

Abstract Patients with mucopolysaccharidosis (MPS), and Morquio A syndrome (MPS IVA) in particular, often report substantial pain burden. MOR-008 was a randomized, double-blind, pilot study assessing the safety and efficacy, including impact on patient-reported pain, of 52 weeks of treatment with elosulfase alfa (at a dose of 2.0 or 4.0 mg/kg/week) in patients with Morquio A syndrome (?7 years old). Assessment of pain at baseline revealed that patients (N = 25) had a mean number of pain locations of 5.7, mean pain intensity score of 4.6 (indicative of medium pain), and a mean number of selected pain descriptors of 7.4 words. Treatment with elosulfase alfa improved subjective pain score (reduced to 3.2), pain locations (reduced by a mean of 1 location), and pain descriptor words (reduced to 4.9 words) over 1 year (52 weeks), suggesting that elosulfase alfa can reduce pain in some patients with Morquio A.

A retrospective study of emergency department potassium disturbances: severity, treatment, and outcomes

OBJECTIVE: Disturbances in potassium (K) levels are relatively common and may be associated with significant morbidity and mortality; however, treatments vary. Our purpose was to determine the incidence, treatments, and outcomes associated with hyperkalemia and hypokalemia in emergency department (ED) patients. METHODS: We performed a structured, retrospective review of electronic medical records of consecutive adult ED patients with K measured while in the ED. Demographic, clinical, and laboratory data as well as treatments, disposition, and in-hospital complications were collected. Univariate and multivariate analyses, presented as adjusted odds ratios, were used to compare outcomes by K levels. RESULTS: Of 100,260 visits in 2014, an ED K level was ordered in 48,827 (49%). A total of 1,738 patients (3.6%) were excluded because of sample hemolysis. The K was low (5.0 mEq/L) in 3.6% of patients. Patients with hyperkalemia were older (64 vs. 49 years, P6 mEq/L. CONCLUSION: Hyperkalemia or hypokalemia occur in 1 of 11 ED patients and are associated with inpatient admission and mortality. Treatment of hyperkalemia varies greatly suggesting the need for evidence-based treatment guidelines.

PubMed inclusion: Clinical and Experimental Emergency Medicine joins the club

No abstract available.

Study design of Real World Evidence for Treatment of Hyperkalemia in the Emergency Department (REVEAL-ED): a multicenter, prospective, observational study

OBJECTIVE: Hyperkalemia affects up to 10% of hospitalized patients and, if left untreated, can lead to serious cardiac arrhythmias or death. Although hyperkalemia is frequently encountered in the emergency department (ED), and is potentially life-threatening, standard of care for the treatment is poorly defined, with little supporting evidence. The main objectives of this observational study are to define the overall burden of hyperkalemia in the ED setting, describe its causes, the variability in treatment patterns and characterize the effectiveness and safety of ED standard of care therapies used in the United States. METHODS: This is an observational study evaluating the management of hyperkalemia in the ED. Two hundred and three patients who presented to the ED with a potassium value ≥5.5 mmol/L were enrolled in the study at 14 sites across the United States. Patients were treated per standard of care practices at the discretion of the patient’s physician. In patients who received a treatment for hyperkalemia, blood samples were drawn at pre-specified time points and serum potassium values were recorded. The change in potassium over 4 hours and the adverse events after standard of care treatment were analyzed. RESULTS AND CONCLUSION: This article describes the background, rationale, study design, and methodology of the REVEAL-ED (Real World Evidence for Treatment of Hyperkalemia in the Emergency Department) trial, a multicenter, prospective, observational study evaluating contemporary management of patients admitted to the ED with hyperkalemia.

Can a Point-of-Care Troponin I Assay be as Good as a Central Laboratory Assay? A MIDAS Investigation

BACKGROUND: We aimed to compare the diagnostic accuracy of the Alere Triage Cardio3 Tropinin I (TnI) assay (Alere, Inc., USA) and the PathFast cTnI-II (Mitsubishi Chemical Medience Corporation, Japan) against the central laboratory assay Singulex Erenna TnI assay (Singulex, USA). METHODS: Using the Markers in the Diagnosis of Acute Coronary Syndromes (MIDAS) study population, we evaluated the ability of three different assays to identify patients with acute myocardial infarction (AMI). The MIDAS dataset, described elsewhere, is a prospective multicenter dataset of emergency department (ED) patients with suspected acute coronary syndrome (ACS) and a planned objective myocardial perfusion evaluation. Myocardial infarction (MI) was diagnosed by central adjudication. RESULTS: The C-statistic with 95% confidence intervals (CI) for diagnosing MI by using a common population (n=241) was 0.95 (0.91-0.99), 0.95 (0.91-0.99), and 0.93 (0.89-0.97) for the Triage, Singulex, and PathFast assays, respectively. Of samples with detectable troponin, the absolute values had high Pearson (R(P)) and Spearman (R(S)) correlations and were R(P)=0.94 and R(S)=0.94 for Triage vs Singulex, R(P)=0.93 and R(S)=0.85 for Triage vs PathFast, and R(P)=0.89 and R(S)=0.73 for PathFast vs Singulex. CONCLUSIONS: In a single comparative population of ED patients with suspected ACS, the Triage Cardio3 TnI, PathFast, and Singulex TnI assays provided similar diagnostic performance for MI.

What's on tablet PC: an introduction to FOAM at home

No abstract available.

Admission rates for emergency department patients with venous thromboembolism and estimation of the proportion of low risk pulmonary embolism patients: a US perspective

OBJECTIVE: Introduction of target specific anticoagulants and recent guidelines encourage outpatient management of low risk patients with venous thromboembolism. We describe hospital admission rates over time for patients presenting to US emergency departments (EDs) with deep vein thrombosis (DVT) and pulmonary embolism (PE) and estimate the proportion of low-risk PE patients who could potentially be managed as outpatients. METHODS: We performed a structured analysis of the National Hospital Ambulatory Medical Care Survey (a nationally representative weighted sampling of US ED visits) database for the years 2006–2010 including all adult patients with a primary diagnosis of DVT or PE. Simplified pulmonary embolus scoring index (sPESI) scores were determined in patients with PE to identify low risk patients. RESULTS: There were an estimated 652,000 and 394,000 ED visits for DVT and PE over the 5-year period (0.17%). Mean (SE) age was 59 (1.3), 50% were female, and 40% were > 65 years. Admission rates for DVT and PE were 52% and 90% respectively with no significant changes over time. In patients with DVT, predictors for admission were age (odds ratio, 1.03 per year of age [95% confidence interval, 1.01 to 1.05]) and race (odds ratio, 4.1 [95% confidence interval, 0.9 to 19.8] for Hispanics and 2.9 [1.2 to 7.4] for Blacks). Of all ED patients with PE, 51% were low risk based on sPESI scores. CONCLUSION: Admission rates for DVT and PE have remained high and unchanged, especially with PE, minorities, and in older patients. Based on sPESI scores, up to half of PE patients might be eligible for early discharge or outpatient therapy.

The Long-Term Effect of an Independent Capacity Protocol on Emergency Department Length of Stay: A before and after Study

PURPOSE: In this study, we determined the long-term effects of the Independent Capacity Protocol (ICP), in which the emergency department (ED) is temporarily used to stabilize patients, followed by transfer of patients to other facilities when necessary, on crowding metrics. MATERIALS AND METHODS: A before and after study design was used to determine the effects of the ICP on patient outcomes in an academic, urban, tertiary care hospital. The ICP was introduced on July 1, 2007 and the before period included patients presenting to the ED from January 1, 2005 to June 31, 2007. The after period began three months after implementing the ICP from October 1, 2007 to December 31, 2010. The main outcomes were the ED length of stay (LOS) and the total hospital LOS of admitted patients. The mean number of monthly ED visits and the rate of inter-facility transfers between emergency departments were also determined. A piecewise regression analysis, according to observation time intervals, was used to determine the effect of the ICP on the outcomes. RESULTS: During the study period the number of ED visits significantly increased. The intercept for overall ED LOS after intervention from the before-period decreased from 8.51 to 7.98 hours [difference 0.52, 95% confidence interval (CI): 0.04 to 1.01] (p=0.03), and the slope decreased from -0.0110 to -0.0179 hour/week (difference 0.0069, 95% CI: 0.0012 to 0.0125) (p=0.02). CONCLUSION: Implementation of the ICP was associated with a sustainable reduction in ED LOS and time to admission over a six-year period.

The Relationship between Carrying Activity and Low Back Pain: A Critical Review of Biomechanics Studies / Jurnal Sains Kesihatan Malaysia

The aim of this review was to systematically explore the underlying musculoskeletal biomechanical mechanisms of carrying and to describe its potential relationship with low back pain. This literature review was carried out using AMED, CINAHL, Compendex and MEDLINE electronic databases. Articles published from 2004 to 2012 were selected for consideration. Articles were considered if at least one measurement of kinetics, kinematics or other related musculoskeletal parameters related to biomechanics were included within the study. After combining the main keywords, 677 papers were identified. However, only 10 studies met all the inclusion criteria. Age, body mass index, gender and level of physical activity were identified as the factors that may influence the biomechanics of carrying activity. Carrying a loaded backpack was reported leading to posterior pelvic tilt, reduced lumbar lordosis, but increased cervical lordosis, thoracic kyphosis and trunk forward lean. Furthermore, while carrying bilaterally, lumbo-pelvic coordination was also reported to be more in-phase, as well as reduced coordination variability in transverse plane. Future studies investigating the biomechanics of a standardized carrying activity for clinical test are recommended.

Lacrimal canaliculitis

Canaliculitis is an uncommon, often misdiagnosed diagnosis because canaliculitis can mimic many other common ocular conditions. Canaliculitis should be appropriately diagnosed and treated to avoid recurrent inflammation and possible obstruction of the upper portion of the lacrimal system. This review will serve as a concise resource to aid in diagnosis and provide updated management options

The Frequency of Reexpansion Pulmonary Edema after Trocar and Hemostat Assisted Thoracostomy in Patients with Spontaneous Pneumothorax

PURPOSE: Several risk factors for development of reexpansion pulmonary edema (REPE) after drainage of pneumothoraces have been reported, but the association between the method of thoracostomy and the development of REPE is unknown. The aim of this study was to compare the frequency of REPE after treatment of spontaneous pneumothorax with trocar or hemostat assisted closed thoracostomy. MATERIALS AND METHODS: We performed a prospective, observational study including 173 patients with spontaneous pneumothorax who visited the emergency department from January 2007 to December 2008. In 2007, patients were treated with hemostat-assisted drainage, whereas patients in 2008 were treated with trocar-assisted drainage. The main outcome was the development of REPE, determined by computed tomography of the chest 8 hours after closed thoracostomy. Outcomes in both groups were compared using univariate and multivariate analyses. RESULTS: Ninety-two patients were included, 48 (42 males) of which underwent hemostat-assisted drainage and 44 (41 males) underwent trocar-assisted drainage. The groups were similar in mean age (24+/-10 vs. 26+/-14 respectively). The frequencies of REPE after hemostat- and trocar-assisted drainage were 63% (30 patients) and 86% (38 patients) respectively (p=0.009). In multivariate analysis, trocar-assisted drainage was the major contributing factor for developing REPE (odds ratio=5.7, 95% confidence interval, 1.5-21). Age, gender, size of pneumothorax, symptom duration and laboratory results were similar between the groups. CONCLUSION: Closed thoracostomy using a trocar is associated with an increased risk of REPE compared with hemostat-assisted drainage in patients with spontaneous pneumothorax.