Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: A multicenter study

Background/Aims@#Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections. @*Methods@#A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated. @*Results@#The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78–0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72–0.77, P10%; this is the cutoff point for the definition of sepsis. @*Conclusions@#Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.

Decreased Health-Seeking Behaviors in People With Depressive Symptoms: The Korea National Health and Nutrition Examination Survey 2014, 2016, and 2018

Objective@#The purpose of this study was to investigate the effects of depressive symptoms on health-seeking behaviors using the large epidemiological study data of the Korea National Health and Nutrition Examination (KNHANES). @*Methods@#Data from the Korea National Health and Nutrition Examination Survey (KNHANES), which is a large-scale national survey, were used in this study. The Patient Health Questionnaire-9 (PHQ-9) was used to assess the depressive state of the participants. Specialized self-reported questionnaires that included questions about health-seeking behaviors were also performed. To examine the relationships between depression and health-seeking behaviors, complex sample logistic regression models with control for covariates were used. @*Results@#There was a significant association between decreased health-seeking behaviors and depressive symptoms in adults (odds ratio [OR]: 3.11, 95% confidence interval [CI]: 2.44–3.96). The association was found to be especially strong in males (OR: 2.63, 95% CI: 1.69–4.10) versus in females (OR: 2.49, 95% CI: 1.90–3.27). With regard to age group, younger adults (19–44 years of age) showed the highest OR (OR: 3.07, 95% CI: 2.12–4.45). @*Conclusion@#Our findings support the idea that there is a significant association between health-seeking behaviors and depressive symptoms in the Korean population. These results suggest that individuals with decreased health-seeking behaviors could be evaluated for depressive symptoms.

Phentermine and Phendimetrazine-Induced Psychotic Disorder and Bipolar Disorder: A Case Series

Objectives@#Recently, weight loss has emerged as a national concern in South Korea, and this has resulted in an increase in the frequency of use of central nervous system (CNS)-stimulating appetite suppressants. This study aimed to collect cases of psychotic disorders and bipolar disorders triggered by phentermine and phendimetrazine and explore the clinical features and courses. @*Methods@#In this retrospective study, we analyzed the electronic medical records of patients and selected eight patients who developed psychotic symptoms and manic symptoms for the first time after taking phentermine and phendimetrazine. All cases were reviewed, and their clinical features and course were summarized. @*Results@#All eight patients developed psychotic symptoms, and one had accompanying manic symptoms. The final diagnosis was appetite-suppressant-induced psychotic disorder in four patients, schizophrenia in three, and appetite-suppressant-induced bipolar disorder in one. In addition, three patients were diagnosed as having substance-use disorder. The key psychotic symptoms of these patients were hallucinations and paranoia. @*Conclusions@#These case findings suggest that phentermine and phendimetrazine can cause psychotic disorder, bipolar disorder, or substance use disorder and that medical professionals and the public should practice caution when prescribing and using these drugs.

Hypertriglyceridemia is a Risk Factor for Fever in Early Acute Non-biliary Pancreatitis / 대한소화기학회지

Background/Aims@#Fever is a common symptom of acute pancreatitis (AP). This study examined the factors associated with fever due to pancreatic inflammation in the early stages of non-biliary AP. @*Methods@#This study analyzed the AP database from Kangwon National University Hospital from January 2018 until April 2021 and identified patients who developed fever within 1 week of hospitalization. Patients with gallstone pancreatitis, pseudocyst, walled-off necrosis, chronic pancreatitis, bacteremia, and other site infections were excluded. The febrile group was compared with the afebrile group. @*Results@#One hundred and fifty-two patients were analyzed, and fever was diagnosed in 79 patients (52.0%). Based on multivariate analysis, fever was positively correlated with hypertriglyceridemia-induced AP (OR 16.8, 95% CI 4.0-70.7, p<0.01) and computed tomography severity index (OR 1.7, 95% CI 1.2-2.6, p<0.01). Recurrent AP was negatively associated with fever (OR 0.3, 95% CI 0.1-0.8, p=0.01). Fever was more frequent in patients with higher initial serum triglyceride (TG) levels than those with lower levels (TG <200 mg/dL; 35.1%, 200≤TG<500 mg/dL; 42.3%, TG ≥500 mg/dL; 88.6%, p<0.01). @*Conclusions@#Hypertriglyceridemia and CT severity index are associated with fever in early non-biliary AP.

Olfactory and Taste Dysfunction in Patients with Asymptomatic and Mildly Symptomatic COVID-19 in Korea

Background and Objectives@#The association between chemosensory dysfunction (CSD) and coronavirus disease 2019 (COVID-19) remains unclear. The aim of the present study was to determine the incidence of olfactory and taste dysfunction in asymptomatic and mildly symptomatic patients with COVID-19 and to evaluate the symptoms associated with CSD in patients with COVID-19.Materials and Method: On March 9, 2020, 309 patients with asymptomatic or mildly symptomatic COVID-19 confirmed by real-time polymerase chain reaction (RT-PCR) were admitted to the No. 7 Community Treatment Center in Korea. An internet-based survey about symptomatology was administered to these patients, with responses obtained from 244 (79.0%). Subjects who completed the survey were enrolled in this study and were categorized into either a CSD group or a normal chemosensory group based on the presence or absence of CSD, respectively. @*Results@#General symptoms, including fever, myalgia, and chills, were most common (29.1%), followed by upper respiratory tract infection (URI) symptoms (20.9%), CSD (20.5%), and nasal symptoms (13.5%). In patients with CSD (n=50), 10 (4.1%) reported no other symptoms. After adjustment for age, sex, past medical history, and other symptoms, general symptoms [odds ratio (OR), 3.63; confidence interval (CI), 1.70-7.76] and nasal symptoms (OR, 7.00; CI, 2.61-18.80) were significantly associated with CSD. @*Conclusion@#The incidence of CSD was relatively high (20.5%) in asymptomatic and mildly symptomatic patients with COVID-19. General symptoms were independent risk factors of CSD, suggesting a sensorineural mechanism for the observed olfactory and taste dysfunction.

Serrated Polyposis Syndrome with a Synchronous Colon Adenocarcinoma Treated by an Endoscopic Mucosal Resection / 대한소화기학회지

Serrated polyposis syndrome (SPS) can transform to malignant lesions through the sessile serrated pathway and traditional serrated pathway. These pathways may cause rapid neoplastic progression compared to the adenoma-carcinoma sequence, which may cause interval colorectal cancer. The authors experienced a case of SPS with a synchronous colon adenocarcinoma that was treated with an endoscopic mucosal resection. In pathology reviews, other parts of the adenocarcinoma showed sessile serrated adenoma. Therefore, patients with SPS have a potential for malignant transformation, highlighting the need for strict colonoscopy surveillance starting at the time of SPS diagnosis.

Liver Dysfunction in Sepsis / 대한소화기학회지

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. During sepsis, the liver has essential roles, such as immune defense and metabolic adaptation to inflammation. In addition, it is a target for sepsis- related injury, including hypoxic hepatitis, cholestasis, drug-induced liver injury, and secondary sclerosing cholangitis in critically ill patients. In particular, the mortality rate due to sepsis is four times higher in patients with cirrhosis, warranting a high index of suspicion for infection, appropriate diagnosis, and prompt antimicrobial treatment. The most recent definition of sepsis (Sepsis-3) no longer uses systemic inflammatory response syndrome (SIRS) and is based on the signs of organ dysfunction, which can be assessed by the Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores. The qSOFA score can be applied at the bedside before any tests and is believed to be suggestive of sepsis when at least two of the following criteria are met: altered consciousness, respiratory rate ≥22/min, and systolic blood pressure ≤100 mmHg. While the qSOFA score performs well in the general population, its role in cirrhotic patients is unclear. This paper briefly reviews the current knowledge of the pathogenesis, definition of sepsis, and sepsis-related liver dysfunction. Furthermore, this review summarizes the clinical applicability of Sepsis-3 in cirrhotic patients.

Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = −0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

Out-of-Hospital Cohort Treatment of Coronavirus Disease 2019 Patients with Mild Symptoms in Korea: an Experience from a Single Community Treatment Center

The outbreak of Coronavirus Disease 2019 (COVID-19) caused a worldwide pandemic. Less than 6 weeks after the first confirmed cases in Korea, the patient number exceeded 5,000, which overcrowded limited hospital resources and forced confirmed patients to stay at home. To allocate medical resources efficiently, Korea implemented a novel institution for the purpose of treating patients with cohort isolation out of hospital, namely the Community Treatment Center (CTC). Herein, we report results of the initial management of patients at one of the largest CTC in Korea. A total of 309 patients were admitted to our CTC. During the first two weeks, 7 patients were transferred to the hospital because of symptom aggravation and 107 patients were discharged without any complication. Although it is a novel concept and may have some limitations, CTC may be a very cost-effective and resource-saving strategy in managing massive cases of COVID-19 or other emerging infectious diseases.

Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = −0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

Out-of-Hospital Cohort Treatment of Coronavirus Disease 2019 Patients with Mild Symptoms in Korea: an Experience from a Single Community Treatment Center

The outbreak of Coronavirus Disease 2019 (COVID-19) caused a worldwide pandemic. Less than 6 weeks after the first confirmed cases in Korea, the patient number exceeded 5,000, which overcrowded limited hospital resources and forced confirmed patients to stay at home. To allocate medical resources efficiently, Korea implemented a novel institution for the purpose of treating patients with cohort isolation out of hospital, namely the Community Treatment Center (CTC). Herein, we report results of the initial management of patients at one of the largest CTC in Korea. A total of 309 patients were admitted to our CTC. During the first two weeks, 7 patients were transferred to the hospital because of symptom aggravation and 107 patients were discharged without any complication. Although it is a novel concept and may have some limitations, CTC may be a very cost-effective and resource-saving strategy in managing massive cases of COVID-19 or other emerging infectious diseases.

Impact of Age at Childbirth on Maternal Mental Health among Premenopausal Women: The 2010–2012 Korean National Health and Nutrition Examination Survey

OBJECTIVE: No reports have investigated the influence of age at first or last childbirth on maternal mental health. The aim of this study was to determine whether there is an association between age at first or last childbirth and the mental health of premenopausal women. METHODS: The data used in this study were collected from the 2010 to 2012 Korea National Health and Nutrition Examination Surveys. A total of 3,370 premenopausal women were considered. The association between childbirth age and maternal mental health factors, including stress, depressed mood, and suicidal ideations were analyzed using multiple logistic regression analyses adjusted for confounding factors. RESULTS: After adjusting confounding factors, younger maternal age at first childbirth was found to be associated with an increase in the prevalence of maternal depressed mood and suicidal ideations. Also, older maternal age at last childbirth was related to an increase in maternal stress, depressed mood and suicidal ideations. CONCLUSION: Both younger first childbirth and older last childbirth maternal age may be risk factors for poor outcomes of premenopausal women’s mental health. These data support the need for comprehensive mental health assessment for premenopausal women who either gave birth at an age too young or too old.

Gender-Specific Association between Alcohol Consumption and Stress Perception, Depressed Mood, and Suicidal Ideation: The 2010–2015 KNHANES

OBJECTIVE: Alcohol drinking can cause various psychiatric and medical diseases. Although women generally consume less alcohol than men, they may be at a greater risk for alcohol-related psychological distress. The aim of the current study is to evaluate whether the association between alcohol consumption and psychological distress, including stress, depressed mood, and suicidal ideation and the risks of psychological distress differ based on gender. METHODS: The cross-sectional study included 31,657 participants (17,915 women and 13,742 men) from the 2010–2013 and 2015 Korea National Health and Nutrition Examination Survey. Alcohol drinking and Alcohol Use Disorders Identification Test (AUDIT) levels were assessed for evaluating the amount of alcohol intake and alcohol-related problems. Self-perception of stress, depressed mood, and suicidal ideation were assessed for evaluating psychological distress. Odds ratio and 95% confidence intervals for psychological distress were calculated using multiple logistic regression models. RESULTS: The risks of psychological distress were not significantly associated with drinking level in both sexes. However, the risks of psychological distress were associated with an increase in AUDIT levels, and there were gender differences in the psychological consequences of alcohol-related problems. The association was more drastic in women, and women showed a significant association even though the severity of drinking problem was low with the exception of stress perception. CONCLUSION: The risks of psychological distress were associated with the severity of alcohol-related problems and women were more likely to be susceptible. Therefore, it is recommended that women even at low-risk for problematic drinking should be screened for psychological distress.

Anxiety and Depression of the Patients with Hematological Malignancies during Hospitalization for Hematopoietic Stem Cell Transplantation

OBJECTIVE: This study aimed to assess the anxiety and depression in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Eighty-seven adult patients with various hematologic diseases, who were scheduled to receive autologous or allogeneic HSCT, were enrolled. The M.D. Anderson Symptom Inventory and the Hospital Anxiety Depression Scale were applied prospectively at hospital admission (D-14), on the day of transplantation (D day), and at 7 (D7) and 14 days (D14) after transplantation. RESULTS: The severity of both anxiety and depressive symptoms increased over time, with a peak at D7, and then showed a downturn at D14. Physical distresses also started with mild intensity at base line, which were continuously aggravated until D7, and then a partial recovery afterwards. Approximately, 52% of the participants had significantly high anxiety or depression before the start of HSCT. The occurrence of aggravation of pain, nausea, shortness of breath, and lack of appetite was associated with the development of anxiety during isolation period. The patients with significant baseline anxiety had higher scores on fatigue and shortness of breath items at D7 compared to those without. CONCLUSION: Our finding suggests the importance of psychiatric approaches, including preventive measures, for the patients undergoing HSCT.

Communication about Death and Confidence Levels concerning Death-Related Issues among Koreans

BACKGROUND: This study investigated the current status of communication about death and confidence levels concerning death-related issues among Korean adults.METHODS: A survey was conducted to ascertain the frequency of death related communication, factors promoting and impeding such communication, and confidence levels concerning death-related issues. Data of 112 participants who completed the survey were analyzed using descriptive statistics, a chi square test, and multiple logistic regression.RESULTS: More than half of the participants (52.7%–84.0%) appeared to have infrequent (never/at least one) conversations about death or death-related issues. Owing to socio-cultural aspects, death-related communication was considered a taboo or an unpleasant topic of conversation. Additionally, indifference toward death inhibited people from communicating; however, personal experiences of death or morbidity and favorable social contexts promoted communication. Overall, the confidence levels concerning death-related issues was low. Only 17.9%–32.2% of the participants were confident/very confident about their preferences concerning death-related issues. The more people talked about death, the more likely they were to develop a confident attitude toward death-related issues (odds ratio, 3.45; 95% confidence interval, 1.37–8.69).CONCLUSION: This study confirmed that communication about death is being withheld among Koreans, and this could possibly lower their level of confidence regarding death-related issues. To achieve death with dignity, a ‘death culture’ needs to be promoted alongside legislation and infrastructure.

Can More Aggressive Treatment Improve Prognosis in Patients with Hepatocellular Carcinoma? A Direct Comparison of the Hong Kong Liver Cancer and Barcelona Clinic Liver Cancer Algorithms

BACKGROUND/AIMS: In addition to the globally endorsed Barcelona Clinic Liver Cancer (BCLC) staging system, other algorithms or staging systems have been developed, including the Hong Kong Liver Cancer (HKLC) staging system. This study aimed to validate the HKLC staging system relative to the BCLC staging system for predicting survival for hepatocellular carcinoma (HCC) patients in Korea. METHODS: From 2004 to 2013, 2,571 patients newly diagnosed with HCC were consecutively enrolled at three Korea University medical centers. RESULTS: Both staging systems differentiated survival well (p < 0.001). However, 1-year and 3-year survival were predicted better using the HKLC system than the BCLC system (area under the receiver operating characteristic curve: 0.869 vs 0.856 for 1 year, p=0.002; 0.841 vs 0.827 for 3 years, p=0.010). In hypothetical survival curves, the HKLC system exhibited better median overall survival than the BCLC system (33.1 months vs 19.2 months). In evaluations of prognosis according to either BCLC or HKLC treatment guidelines, risk of death was reduced in the group following only HKLC guidelines compared with the group following only BCLC guidelines (hazard ratio, 0.601; 95% confidence interval, 0.443 to 0.816; p=0.001). CONCLUSIONS: Although both staging systems predicted and discriminated HCC prognoses well, the HKLC system showed more encouraging survival benefits than the BCLC system.

Feasibility of Psychosocial Distress Screening and Management Program for Hospitalized Cancer Patients

OBJECTIVE: Although the diagnosis and treatment of cancer is associated with psychosocial distress, routine distress screening is difficult in hospitalized oncology settings. We developed a consecutive screening program for psychosocial distress to promote psychiatric treatment of cancer patients and evaluated the feasibility of our program by Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS). METHODS: Among 777 cancer inpatients recruited from the Catholic Comprehensive Institute of Seoul St. Mary's Hospital, 499 agreed to complete primary distress screening through DT. We conducted secondary distress screening through HADS in 229 patients who had high scores of DT. RESULTS: Of the 499 participants, 270 patients with low scores of DT were included in the distress education program. 229 patients with high scores of DT received secondary distress screening through HADS. Among 115 patients with low scores of HADS, 111 patients received distress management. Among 114 patients with high scores in the secondary distress screening, 38 patients received psychiatric consultation service whereas 76 patients refused psychiatric consultation. CONCLUSION: Using consecutive screening for psychosocial distress appeared to be feasible in an inpatient oncology setting. Nevertheless, the low participation rate of psychiatric consultation service in cancer patients with high distress level should be improved.

Complete response of advanced hepatocellular carcinoma to sorafenib: another case and a comprehensive review

Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.

Nonerosive Reflux Disease / 대한내과학회지

Nonerosive reflux disease (NERD) is a distinct presentation of gastroesophageal reflux disease (GERD). NERD is commonly defined as the presence of classical GERD symptoms in the absence of esophageal mucosal erosions/breaks on upper endoscopy. Within the spectrum of GERD, the pathophysiological and clinical characteristics distinguishing NERD and erosive esophagitis remain a matter for debate. Recent research on NERD has focused on understanding the pathophysiology and natural history. Given the increased incidence of NERD in Korea, we reviewed the concept of NERD and its relationship to GERD and functional gastrointestinal disorders.

Altitude May Contribute to Regional Variation in Methamphetamine Use in the United States: A Population Database Study

OBJECTIVE: Methamphetamine (MA) use rates in the United States (US) have consistently demonstrated geographical variation and have been higher in the West and Midwest. This uneven pattern of use could be explained by regional differences in MA manufacturing and distribution, but may also result from differences in altitude. The hypobaric hypoxia found at high altitude alters neurotransmitter synthesis in the brain, which may contribute to MA use. The present study investigated the relationship between mean altitude and MA use rate in the 48 contiguous US states and the District of Columbia. METHODS: State-level estimates of past year MA use were extracted from the National Survey on Drug Use and Health report. The mean altitude of each state was calculated using the Shuttle Radar Topography Mission altitude data set. RESULTS: There was a significant positive correlation between mean state altitude and MA use rate (r=0.66, p<0.0001). Multivariate linear regression analysis showed that altitude remained a significant predictor for MA use rate (beta=0.36, p=0.02), after adjusting for age, ethnicity, education, socioeconomic level, employment, MA laboratory incidents, subpopulations, and other substance use. CONCLUSION: Altitude appears to a possible contributing factor for regional variation of MA use in the US. Further studies will be required to determine biological changes in neurotransmission resulting from chronic mild hypoxia at high altitude in MA users.