Pharmacokinetics of desflurane uptake and disposition in piglets.

Introduction: Many respiratory but few arterial blood pharmacokinetics of desflurane uptake and disposition have been investigated. We explored the pharmacokinetic parameters in piglets by comparing inspiratory, end-tidal, arterial blood, and mixed venous blood concentrations of desflurane. Methods: Seven piglets were administered inspiratory 6% desflurane by inhalation over 2 h, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were detected using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine desflurane concentrations by gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min during each uptake and disposition phase. Respiratory and hemodynamic parameters were measured simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between the arterial and pulmonary artery blood concentrations by the cardiac output. Results: The rates of desflurane body uptake increased considerably in the initial 5 min (79.8 ml.min-1) and then declined slowly until 120 min (27.0 ml.min-1). Similar characteristics of washout were noted during the subsequent disposition phase. Concentration-time curves of end-tidal, arterial, and pulmonary artery blood concentrations fitted well to zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best fitted using a two-compartment model. After 2 h, only 21.9% of the desflurane administered had been eliminated from the body. Conclusion: Under a fixed inspiratory concentration, desflurane body uptake in piglets corresponded to constant zero-order infusion, and the 2-h disposition pattern followed first-order kinetics and best fitted to a two-compartment model.

Preoperative Use and Discontinuation of Traditional Chinese Herbal Medicine and Dietary Supplements in Taiwan: A Cross-Sectional Questionnaire Survey.

Traditional Chinese herbal medicine has widespread use in Taiwan. This cross-sectional questionnaire survey investigates the preoperative use and discontinuation of Chinese herbal medicine and dietary supplements among Taiwanese patients. We obtained the types, frequency, and sources of Chinese herbal remedies and supplements used. Among 1428 presurgical patients, 727 (50.9%) and 977 (68.4%) reported the use of traditional Chinese herbal medicine and supplements in the past one month, respectively. Only 17.5% of the 727 patients stated discontinuation of herbal remedies 4.7 ± 5.1 (1-24) days before the surgery, and 36.2% took traditional Chinese herbal medicine with concomitant physician-prescribed Western medicine for their underlying diseases. The most commonly used Chinese herbs are goji berry (Lycium barbarum) (62.9%) and Si-Shen-Tang (48.1%) in single and compound forms, respectively. The presurgical use of traditional Chinese herbal medicine was common in patients undergoing gynecologic (68.6%) surgery or diagnosed with asthma (60.8%). Women and those with a high household income had a greater tendency to use herbal remedies. This study demonstrates the high proportion of the presurgical use of Chinese herbal remedies and supplements along with physician-prescribed Western medicine in Taiwan. Surgeons and anesthesiologists should be aware of the potential adverse effects of drug-herb interaction for Chinese patients.

Prescription Opioid Use among Patients with Chronic Noncancer Pain before and after the COVID-19 Outbreak in Taiwan: A Multicenter Prospective Observational Study.

BACKGROUND: The COVID-19 outbreak disrupted medical access for patients receiving chronic opioid therapy. This study investigated their prescription opioid dosages before and after the 2020 outbreak in Taiwan. METHODS: A prospective questionnaire survey was conducted among registered outpatients receiving long-term opioids before July 2019 in Taiwan. The questionnaire included items from the Taiwanese Brief Pain Inventory and quality of life assessment. Follow-up surveys in outpatient departments through October 2020 were conducted to collect opioid prescription data. RESULTS: After a mean of 531 days, the questionnaire responses of 103 of the initial 117 respondents were reviewed. Daily opioid doses decreased for 31 respondents (30.1%), remained roughly equivalent (defined as ±2.5%) for 27 (26.2%), and increased for 45 (43.7%) after the first wave of the pandemic. The use of strong opioids and nonopioid medications did not significantly differ among the three groups, but less fentanyl patch use was noted in the decreased-dose group after the outbreak. More than 70% of the patients received daily high-dose opioids (≥90 morphine milligram equivalents); moreover, 60% reported constipation. No deaths due to opioid overdose occurred during the study period. CONCLUSIONS: The COVID-19 outbreak in 2020 did not interrupt access to long-term opioid prescriptions for most registered patients with chronic pain in Taiwan. Less fentanyl patch use was observed in participants whose opioid dose was tapering.

Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) depletes endogenous Vitamin C and generates oxidative stress in cardiac surgery. This study aimed to clarify whether Vitamin C supplementation reduces oxidant production and improves erythrocyte deformability in cardiac surgery with CPB. In a randomized and controlled design, 30 eligible patients undergoing cardiac surgery with hypothermic CPB were equally assigned to the Vitamin C group and control group. Subjects of the Vitamin C group and control group received an intravenous infusion of Vitamin C 20 mg·kg-1 and a placebo during rewarming period of CPB, respectively. We measured the plasma level of reactive oxygen species (ROS) and phosphorylation levels of non-muscle myosin IIA (NMIIA) in erythrocyte membrane, as an index of erythrocyte deformability, before and after CPB. Vitamin C supplementation attenuated the surge in plasma ROS after CPB, mean 1.661 ± standard deviation 0.801 folds in the Vitamin C group and 2.743 ± 1.802 in the control group. The tyrosine phosphorylation level of NMIIA after CPB was upregulated in the Vitamin C group compared to the control group, 2.159 ± 0.887 folds and 1.384 ± 0.445 (P = 0.0237). In addition, the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and focal adhesion kinase (FAK) in erythrocytes was concurrently enhanced in the Vitamin C group after CPB. The phosphorylation level of endothelial nitric oxide synthase in erythrocytes was significantly increased in the Vitamin C group (1.734 ± 0.371 folds) compared to control group (1.102 ± 0.249; P = 0.0061). Patients receiving Vitamin C had lower intraoperative blood loss and higher systemic vascular resistance after CPB compared to controls. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability via VASP/FAK signaling pathway in erythrocytes during CPB.

Discrepant End-Tidal Concentrations of Sevoflurane at the Same A-Line Autoregressive Index Level during Induction of General Anesthesia: An Observational Study.

BACKGROUND: The A-Line Autoregressive Index (AAI), which is derived from auditory evoked potentials, has been used for determining anesthetic depth. This study verified the correlation between AAI values and the corresponding end-tidal concentrations of sevoflurane during general anesthesia induction. METHODS: Thirty young male adults undergoing elective minor orthopedic surgery were sequentially allocated to receive inspiratory 3%, 5%, or 6% sevoflurane for mask induction, followed by mechanical ventilation after tracheal intubation. The inspiratory, end-tidal and estimated jugular bulb concentrations of sevoflurane were recorded at three target AAI values: below 20, below 10, and at the start of burst suppression. RESULTS: The mean time to loss of consciousness in the 6% sevoflurane group was shorter than that in the 5% and 3% groups; however, the groups had comparable AAI values (range: 16-45). The 6% group had a higher end-tidal concentration (4.5% ± 0.2% vs. 3.8% ± 0.2%, p < 0.05) than did the 5% group, despite having the same target anesthetic levels by AAI score ≤10, whereas the estimated jugular bulb concentrations were comparable (1.9% vs. 1.9%) in both groups. CONCLUSIONS: Following mechanical ventilation with inspiratory 3%, 5%, or 6% sevoflurane, the end-tidal concentrations were discrepant at the same end points of AAI levels, despite similar estimated jugular bulb concentrations of sevoflurane. Thus, conventional alveolar concentration may overestimate anesthesia depth during rapid wash-in of sevoflurane.

Gender Differences in Depression and Sex Hormones among Patients Receiving Long-Term Opioid Treatment for Chronic Noncancer Pain in Taiwan-A Multicenter Cross-Sectional Study.

BACKGROUND: Long-term use of opioids for chronic noncancer pain is associated with sex hormone disturbances. The interferences with sex hormones, sexual function, and depression were investigated in patients with chronic noncancer pain. METHODS: A cross-sectional multicenter survey was conducted on 170 officially registered outpatients receiving long-term opioid treatment in nine medical centers in Taiwan between October 2018 and July 2019. Serum sex hormone levels were examined after the collection of self-administered questionnaires containing the Taiwanese version of the Brief Pain Inventory, depressive status, and sexual function interference. RESULTS: Among 117 (68.8%) questionnaire responses from 170 enrolled outpatients, 38 women and 62 men completed the sex hormone tests, among whom only 23 (23%) had previously received blood hormone tests. Low serum total testosterone levels were detected in 34 (89.5%) women (<30 ng/dL) and 31 (50%) men (<300 ng/dL). Over 60% of women and men reported reduced sexual desire and function despite a nearly 50% reduction in pain intensity and daily function interference over the previous week after opioid treatment. Women generally had higher risks of a depression diagnosis (p = 0.034) and severe depressive symptoms (p = 0.003) and nonsignificantly lower opioid treatment duration (median 81 vs. 120 months) and morphine milligram equivalent (median 134 vs. 165 mg/day) compared with men. CONCLUSIONS: This survey demonstrated the high prevalence of depression diagnosis, low sex hormone levels, and reduced sexual function among Taiwanese patients with chronic noncancer pain receiving prolonged opioid therapy. Regular hypogonadal screenings are recommended for further management.

Endovascular aortic repair is a cost-effective option for in-hospital patients with abdominal aortic aneurysm.

BACKGROUND: To investigate the cost-effectiveness of endovascular aortic repair (EVAR) versus open aortic repair (OAR) for abdominal aortic aneurysm (AAA) using incremental costs per decreased in-hospital mortality rate gained through our patients' cohort. METHODS: Medical records and healthcare costs of patients with AAA hospitalized between 2010 and 2015 were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Multiple regression analysis was applied to adjust for confounding factors and to compare the differences in postoperative clinical outcomes between patients who received EVAR and OAR. The incremental cost-effectiveness ratio (ICER) of EVAR was determined based on the healthcare cost obtained from the analyzed data. RESULTS: A total of 2803 AAA patients were identified (n = 559 with ruptured AAA and n = 2244 unruptured AAA). Patients with ruptured AAA who underwent EVAR compared with OAR patients had shorter hospital and intensive care unit (ICU) stays (all p < 0.05). For patients with unruptured AAA, those who received EVAR compared with OAR, the adjusted odds ratio (aOR) of postoperative complications and in-hospital mortality were 0.371 and 0.447 (all p < 0.05). The total direct surgical costs and medical expenses during hospitalization in all AAA patients were higher for the EVAR group; however, ICER was <1 per capita gross domestic product. Stratification by age groups further suggested that ICER for patients with unruptured AAA who received EVAR, compared with OAR, decreased with age. CONCLUSION: Total direct medical costs were higher for AAA patients receiving EVAR regardless of rupture status; however, the cost is offset by lower odds of postoperative complications and in-hospital mortality. The observed decrease in ICER with age and EVAR use warrants further analysis. Our findings further validate the use of EVAR over OAR. These results provides supporting evidence for physicians and patients with AAA to inform shared decision making regarding endovascular or OAR options.

Anesthesia services in Taiwan: A nationwide population-based study.

BACKGROUND: This study was conducted to provide an overview of anesthesia services in Taiwan from 2001 to 2010. METHODS: A retrospective population-based analysis was performed using data from Taiwan's National Health Insurance Research Database for the period 2001 to 2010. The results were stratified by patient sex, patient age, anesthesia type, and hospital setting. Categorical data are presented as totals and percentages. Linear regression was performed to analyze the anesthesia trends. RESULTS: The annual use of anesthesia increased continually from 964,440 instances in 2001 to 1,073,160 in 2010, totaling 10,076,600 cases with a total cost of 25.4 billion USD. The overwhelming majority (83.9%) of anesthesia cases was for anesthesia in an inpatient setting; general anesthesia accounted for 73.8% of anesthesia cases, and female patients outnumbered male patients (52.4% vs 47.6%). The average number of anesthesia cases was 44.2 per thousand of the population annually, but this percentage was much higher in elderly people (100.9 cases per thousand people annually). The annual number of anesthesia cases per thousand of the population increased from 104.4 in 2001 to 113.0 in 2010 in the oldest group (>80 years). By contrast, a considerable decline in use of anesthesia was discovered over the study period among those aged younger than 18 years. CONCLUSION: The use of anesthesia services in Taiwan has increased over the years. The relationships of age with anesthesia volume and cost were found to follow an inverse U-shaped pattern. Elderly people used anesthesia services more frequently. The planning of geriatric anesthesia services deserves attention, especially in continually aging societies such as Taiwan.

Knowledge, attitude, and barriers regarding prescribing long-term opioids among Taiwan physicians treating officially registered patients with chronic noncancer pain.

BACKGROUND: Prescribing opioids for patients with chronic noncancer pain (CNCP) remains controversial. This study surveyed Taiwanese physicians who were clinically treating CNCP outpatients with long-term opioids. METHODS: Anonymous questionnaires investigating the clinical practices, opioid knowledge, attitude, and barriers regarding the prescription of long-term opioids were delivered to 66 physicians treating CNCP outpatients who were officially registered and monitored by the Taiwan Food and Drug Administration in 2011. RESULTS: All 66 (100%) physicians responded to the survey, comprising 41 (62%) board-certified pain specialists and 25 (38%) nonpain board-certified physicians. Pain specialists treated a greater number of CNCP outpatients and attended more CNCP training courses than nonpain board-certified physicians (97.6% vs. 56.0%, p < 0.001). Most of pain specialists stated that they were familiar with the Taiwan's narcotic regulations for CNCP patients (92.7% vs. 68.0%, p = 0.015). In addition, pain specialists were less likely to skip or reduce the dosage and duration of opioid prescriptions (22.0% vs. 36.0%, p < 0.001). By contrast, nonpain board-certified physicians had significantly less knowledge and a more negative attitude toward opioid prescription. The major perceived barriers were physician's reluctance to prescribe opioids (78% vs. 92%) and an inadequate knowledge of pain management (73% vs. 84%) among all physicians. CONCLUSION: Among the Taiwanese physicians treating the officially registered CNCP patients, nonpain board-certified physicians had fewer patients, less knowledge, and an increased negative attitude toward long-term opioid prescriptions. Better education on chronic pain management is needed for improvement of clinical practice.

Health-related quality of life in patients with abdominal aortic aneurysm undergoing endovascular aneurysm repair: A cross-sectional study.

BACKGROUND: Endovascular aneurysm repair (EVAR) has become a common surgical treatment for abdominal aortic aneurysm (AAA), and postoperative health-related quality of life (HRQoL) is drawing increasing attention. Most studies compare HRQoL in EVAR patients and open aneurysm repair patients, while few studies have investigated HRQoL in EVAR patients versus the general population. This study aimed to investigate whether HRQoL differs between patients with EVAR patients and the general population. METHODS: EVAR patients were recruited from a medical center in northern Taiwan. General population subjects and the EVAR patients were paired based on age and sex, and a simple random sampling method was used for sampling at 2:1. In this study, we used the World Health Organization Quality of Life Scale Abbreviated Version, Taiwan Version to investigate HRQoL. A multivariate regression model was used to analyze intergroup differences related to facets and domains. RESULTS: A total of 58 patients with EVAR and 116 individuals from the general population were included in this study. The EVAR patients' mean scores for overall QoL and the physical domain, psychological domain, social relations domain, and environment domain were 3.79, 15.53, 15.00, 14.93, and 15.57, respectively, and all of these scores were significantly higher than those in the general population. In addition, the ß values (ß = 0.21, 0.73, 1.83, 0.81, and 2.62, respectively) of the EVAR patients were also significantly higher in the multivariate analysis. The findings showed that a high education level and nonsmoking status were associated with higher HRQoL, while unemployment was associated with lower HRQoL. CONCLUSION: EVAR patients had higher HRQoL than the general population, indicating that patients with AAA have a high likelihood of recovering and enjoying high HRQoL if they receive appropriate medical procedures and nursing education.

Glucose reduces the osmopressor response in connection with the tyrosine phosphorylation of focal adhesion kinase in red blood cells.

Glucose ingestion attenuates the water ingestion-induced increase in the total peripheral vascular resistance and orthostatic tolerance. We investigated the gastrointestinal physiology of glucose by examining the effect of glucose ingestion on the functional expression of focal adhesion kinase (FAK) in red blood cell (RBC) membrane. This study was performed in 24 young, healthy subjects. Blood samples were collected at 5 min before and 25 min and 50 min after an ingestion of 10% glucose water 500 mL, water 500 mL, or normal saline 500 mL. We determined glucose and osmolality in plasma, and phosphorylation of aquaporin 1 (AQP1), glucose transporter 1 (Glut1), and FAK in RBC membrane. Our results showed that glucose ingestion reduced the rise of peripheral vascular resistance after water ingestion and upregulated the serine phosphorylation of Glut1. It also lowered both the serine phosphorylation of FAK and tyrosine phosphorylation of AQP1, compared with the ingestion of either water or saline. In an ex vivo experiment, glucose activated the Glut1 receptor and subsequently reduced the expression of FAK compared with 0.8% saline alone. We concluded that glucose activates Glut1 and subsequently lowers the functional expression of FAK, a cytoskeleton protein of RBCs. The functional change in the RBC membrane proteins in connection with the attenuation of osmopressor response may elucidate the pathophysiology of glucose in postprandial hypotension.

Evaluation of the pain intensity differences among hospitalized cancer patients based on a nursing information system.

Evaluating the absolute difference in pain intensity and the percentage difference in pain intensity could facilitate an understanding of pain reduction among cancer patients during repeated hospitalizations. Examinations of the absolute differences in pain intensity and the percentage differences in pain intensity according to the worst pain intensity and last evaluated pain intensity before discharge are lacking. The aim of this study was to evaluate the absolute and percentage difference in pain intensities among cancer patients with moderate or severe pain from their 1st to 18th hospitalizations from 2011-2013. A population-based retrospective cohort study was conducted. Pain intensity was assessed using scales and was recorded in a nursing information system. The absolute and percentage difference in pain intensities were examined via the one-sample Kolmogorov-Smirnov test, and group differences in moderate or severe pain were evaluated with the Mann-Whitney U test. For moderate pain patients, the mean absolute difference in pain intensity was 1.52, and the percentage difference in pain intensity was 29.0%; both these values were significant. More significant changes in the absolute and percentage difference in pain intensities were associated with severe pain patients. Both the average absolute difference in pain intensity (3.09) and the percentage difference in pain intensity (38.5%) in patients with severe pain were significantly higher than the average absolute difference in pain intensity (1.52) and the percentage difference in pain intensity (29.0%) in patients with moderate pain. Cancer patients with moderate and severe pain experienced pain reductions of approximately 30% and 40%, respectively. Early pain management intervention in patients with severe pain is necessary to achieve an obvious analgesic effect, and the formula of the percentage difference in pain intensity should be incorporated into the nursing information system to alert clinicians for early detection of the effectiveness of cancer pain management.

Knowledge, Attitude and Practice Survey of Prescribing Opioids for Chronic Noncancer Pain in Taiwan-Comparison of Pain and Non-Pain Physicians.

BACKGROUND: Prescribing opioids for chronic noncancer pain (CNCP) has been strictly regulated in Taiwan. This study was undertaken to survey pain and non-pain related physicians' knowledge, attitudes, and practices regarding prescribing opioids for CNCP. METHODS: A questionnaire survey was conducted in this comparison study. All 66 physicians who were treating officially registered CNCP outpatients were visited and completed anonymous questionnaires. The other physicians (anesthesiologists, oncologists, and non-pain physicians) were surveyed by a mailed questionnaire. RESULTS: A total of 266 (75%) questionnaires were received from 355 board-certified physicians. More CNCP physicians (81.8%) and anesthesiologists (69.7%) had received prior CNCP-related training courses than had oncologists (21.2%) and non-pain physicians (10.3%). Varied proportions of physicians by type were unfamiliar with the Taiwan opioid regulations (16.7-86.8%) and would accordingly skip or reduce dosage of opioid prescriptions (27.3-73.5%). In addition, non-pain physicians had a significantly lower knowledge level, more negative attitudes, and greater hesitation about prescribing opioids compared to the pain-related physicians (P < 0.001). CNCP physicians who had received CNCP-related training courses had a higher knowledge score than did those not receiving training (P = 0.002). Overall, the leading barriers for prescribing opioids were inadequate knowledge of pain management (76%), physician reluctance (73%), and family reluctance (78%). CONCLUSION: There are substantial knowledge gaps, negative attitudes, and hesitation toward prescribing long-term opioids for CNCP patients by physicians in Taiwan, suggesting that efforts are needed to improve postgraduate education regarding adequate opioid management for CNCP.

Analgesic effects of repetitive transcranial magnetic stimulation on modified 2010 criteria-diagnosed fibromyalgia: Pilot study.

AIM: Fibromyalgia is often comorbid with depression, and less than half those patients achieve satisfactory improvement after adequate pharmacological intervention. The investigation of repetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex for modified-2010 American College of Rheumatology (ACR) fibromyalgia and major depressive disorder (MDD) is still in its infancy. METHODS: In this double-blind, randomized, sham-control study, subjects diagnosed with ACR-2010 fibromyalgia and DSM-IV-TR MDD were recruited and received either active or sham interventions for 2 weeks. Hamilton Depression Rating Scale (HDRS) and the 10-cm visual analogue pain scale were evaluated at baseline, week 1, and week 2. Multivariable generalized estimating equations analysis was performed for the association between depression and pain scores at each checkpoint. RESULTS: Twenty subjects were recruited. There was a significant difference over the 2 weeks between the rTMS and sham stimulation groups (P = 0.029), but subgroup analyses were further performed due to significant interaction of group and HDRS on pain outcomes (P = 0.020). The active group had significant improvement in pain at week 2 compared with week 1 (P = 0.021), but the control group did not have any improvement in pain (P = 0.585). Of the mild-moderate depression patients, the pain score in the active group was significantly lower than in the sham group at week 1 (P = 0.001) and at week 2 (P < 0.001). For the severe depression group, there was significantly lower pain over the 2 weeks in the active group (P = 0.045) but the sham group had significantly relapsing pain at week 2 (P < 0.001). CONCLUSION: Left prefrontal rTMS has an analgesic effect in modified-ACR 2010-defined fibromyalgia and MDD patients. Further investigation is required, however, in order to determine how to regulate the different rTMS treatment protocols according to individual baseline depression severity in patients with MDD and fibromyalgia.

Gender difference in long-term use of opioids among Taiwan officially registered patients with chronic noncancer pain.

Research regarding sex or gender difference in chronic pain proliferated in this decade. This study was to analyze gender difference in Taiwan patients receiving long-term opioids for chronic noncancer pain.An observational cross-sectional survey was conducted among the registered outpatients by the Taiwan Food and Drug Administration. Participants completed a self-report questionnaire, including the Taiwanese version of Brief Pain Inventory and enquiry regarding sexual activities, depressive symptoms, and misuse behaviors.In total, 68 female and 142 male patients were analyzed. Both pain intensity and daily function interference reduced comparably (around 50%) between women and men after taking opioids in the past 1 week. The opioid-related adverse effects, including constipation, decreased sexual desire and satisfaction, and misuse behaviors were not significantly different. Women were exceedingly diagnosed with depression (67.7% vs 49.3%, P = .012) and had a higher mean depressive symptom score in the past 1 month, especially among those age <40 years (23.3 vs 11.9, P = .009), as compared with men. In addition, women had a lower mean self-rated health score (37.9 vs 44.3, P = .047). The mean morphine equivalent dose was significantly lower in women (131.6 vs 198.2 mg/day, P = .008), which was not correlated with their depressive scores.Gender differences in the effectiveness and adverse effects of long-term opioids were not found among Taiwan registered outpatients with chronic noncancer pain. However, more female patients inclined to have a coexisting depression diagnosis, depressive symptoms, and a lower perceived health score, needing regular screening and closer monitoring.

Clinical risk factors of extracorporeal membrane oxygenation support in older adults.

BACKGROUND: The ageing population and the expected increase in the number of elderly patients make an evidence-based assessment of Extracorporeal Membrane Oxygenation (ECMO) therapy in old patients progressively more important. Veno-arterial (VA) ECMO results for patient aged <65 years is well known. However, the risk profile and in-hospital prognosis of advanced age patients with ECMO still need more investigation. The aim of this study was to identify risk factors that predicted the outcomes for elderly patients who received VA-ECMO. METHODS: In this retrospective study, medical records for patients with ECMO aged 65 years and over were collected between 2009 and 2012 at a tertiary hospital. RESULTS: A total of 99 patients (mean age: 76.4±6.4 years) were included. The most common condition requiring VA-ECMO support was cardiogenic shock. Among survivors on VA-ECMO, 28 (28.3%) patients were successfully weaned from support. Thirteen (13.1%) patients were successfully discharged. We found that cardiogenic shock (OR = 3.158, P = 0.013), acute physiology and chronic health evaluation II (APACHE II) score (OR = 1.147, P<0.001), and simplified acute physiology score II (SAPS II) score (OR = 1.054, P = 0.001) were risk factors associated with survival on VA-ECMO. By using the areas under the receiver operating characteristic (AUC) curve, the APACHE II score and SAPS II score displayed acceptable discriminative power (AUC 0.722; 0.715, respectively). CONCLUSION: Our findings indicate that the risk of mortality increases with cardiogenic shock, higher APACHE II score, and higher SAPS II score. These risk factors can be utilized as potential predictors to identify the potential candidates for ECMO support.

Effects of SPAK on vascular reactivity and nitric oxide production in endotoxemic mice.

Vasoplegia impedes therapeutic interventions to restore vascular tone, leading to severe hypotension, poor tissue perfusion, and multiple organ failure in septic shock. High levels of circulating nitric oxide (NO) play a crucial role in endotoxin-induced vascular hyporeactivity. Proinflammatory cytokines have been implicated in the induction of inducible NO synthase and overproduction of NO. Anti-inflammatory therapy can diminish NO formation and improve vascular hyporeactivity in septic shock. STE20/SPS1-realted proline/alanine-rich kinase (SPAK) has been reported to activate mitogen-activated protein kinase and contribute to intestinal inflammation. Thus, we evaluated the roles of SPAK in NO production and vascular hyporeactivity in endotoxemic animals. Male wild-type and SPAK deficiency mice were intraperitoneally administered vehicle or Escherichia coli lipopolysaccharide (LPS, 50mg/kg). The changes of systolic blood pressure and plasma nitrate and nitrite levels were measured during the experimental period. Thoracic aortas were exercised to assess vascular reactivity and SPAK expression. In the present study, mice in endotoxin model showed severe hypotension and hyporeactivity to serotonin, phenylephrine (PE), and acetylcholine in the aortic rings. Phosphorylated SPAK expression in the aorta and NO levels in the plasma were also increased in animals with endotoxic shock. However, deletion of SPAK not only reduced the elevation of NO levels but also improved vascular hyporeactivity to serotonin and PE in endotoxemic mice. Taken together, SPAK could be involved in the NO overproduction and vascular hyporesponsiveness to vasoconstrictors in endotoxic shock. Thus, inhibition of SPAK could be useful in the prevention of endotoxin-induced vascular hyporeactivity.

Voluntary attendance of small-group brainstorming tutoring courses intensify new clerk's "excellence in clinical care": a pilot study.

BACKGROUND: Clerkship provides a unique way of transferring the knowledge and skills gathered during medical school's curriculum into real-ward clinical care environment. The annual program evaluation has indicated that the training of clerks in diagnostic and clinical reasoning skills needed to be enhanced. Recently, "clinical excellence" program have been promoted in our institution to augment the excellence in clinical care of new clerks. Current study aims to evaluate whether this pilot program improve the "clinical excellence" of new clerks. METHODS: In a pilot study, groups of new clerks in years 2013 and 2014 voluntarily attended either a small-group brainstorming course or a didactic classroom tutoring courses as part of their 3-month internal medicine clinical rotation block. A third group of new clerks did not join either of the above courses and this group served as the control group. Pre-block/post-block self-assessment and post-block 5-station mini-Objective Subjective Clinical Examinations (OSCEs) were used to evaluate the effectiveness of these two additional courses that trained diagnostic and clinical reasoning skills. RESULTS: Overtime, the percentages of new clerks that attended voluntarily either the small-group brainstorming or classroom tutoring courses were increased. Higher post-block self-assessed diagnostic and clinical reasoning skill scores were found among individuals who attended the small-group brainstorming courses compared to either the didactic group or the control group. In a corresponding manner, the small-group brainstorming group obtained higher summary OSCEdiag and OSCEreason scores than either the didactic group or control group. For all basic images/laboratory OSCE stations, the individual diagnostic skill (OSCEdiag) scores of the small-group brainstorming group were higher than those of the didactic group. By way of contrast, only the clinical reasoning skill (OSCEreason) scores of the basic electrocardiogram and complete blood count + biochemistry OSCE station of thesmall-group brainstorming group were higher than those of the didactic group. Among the small-group brainstorming group, clerks with higher cumulative learning hours (>30-h) had significant higher OSCEdiag and OSCEreason scores (>400) than those with less cumulative learning hours. CONCLUSION: Our pilot study provides a successful example of the use of a small-group tutoring courses for augmenting the diagnostic and clinical reasoning skills of new clerks. The positive results obtained during the initial 2-year long pilot "clinical excellence" program have encouraged the formal implementation of this course as part of the clerkship curriculum.

Long-term use of opioids in 210 officially registered patients with chronic noncancer pain in Taiwan: A cross-sectional study.

BACKGROUND/PURPOSE: Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids. METHODS: An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine. RESULTS: For 210 of 328 outpatients (64.0%), the median pain duration was 96 months and opioid treatment duration was 57 months. The median morphine equivalent dose was 150 mg/d, with 30.5% of patients exceeding the daily watchful dose, defined as 200 mg of morphine equivalent dose. Pain reduction after taking opioids was ∼50% in the past week. The top three diagnoses were chronic pancreatitis, spinal cord injury, and neuralgia. The leading side effects were constipation (46.7%), and decreased sexual desire (69.5%) and satisfaction (57.9%). Depression was currently diagnosed in 55.2% of patients. Twenty patients (9.5%) displayed at least one aberrant behavior in the past month. Only 76 (36.2%) patients had ever received nerve block procedures, and 118 (56.2%) tried complementary and alternative medicine. CONCLUSION: This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose.