Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning.

BACKGROUND: Functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. METHODS: Resting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. RESULTS: Regardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94-100.00) and 88.89% (CI=63.96-100.00) in the cross-validation and test dataset, respectively. LIMITATIONS: The sample size was moderate, and features for machine learning were based on group differences. CONCLUSIONS: Long-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.

The fluid property dependency on micro-fluidic characteristics in the deposition process for microfabrication.

The droplet impingement into a cavity at micrometer-scale is one of important fluidic issues for microfabrications, e.g. the inkjet deposition process in the PLED display manufacturing. The related micro-fluidic behaviors in the deposition process should be carefully treated to ensure the desired quality of microfabrication. The droplets generally dispensing from an inkjet head, which contains an array of nozzles, have a volume in several picoliters, while each nozzle responds very quickly and jets the droplets into cavities on substrates with micrometer size. The nature of droplet impingement depends on the fluid properties, the initial state of droplet, the impact parameters and the surface characteristics. The commonly chosen non-dimensional numbers to describe this process are the Weber number, the Reynolds number, the Ohnesorge number, and the Bond number. This paper discusses the influences of fluid properties of a Newtonian fluid, such as surface tension and fluid viscosity, on micro-fluidic characteristics for a certain jetting speed in the deposition process via a numerical approach, which indicates the impingement process consists of four different phases. In the first phase, the droplet stretching outwards rapidly, where inertia force is dominated. In the second phase, the recoiling of droplet is observed, where surface tension becomes the most important force. In the third phase, the gravitational force pulls the droplet surface towards cavity walls. The fourth phase begins when the droplet surface touches cavity walls and ends when the droplet obtains a stable shape. If the fluid viscosity is relatively small, the droplet surface touches cavity walls in the second phase. A stable fluid layer would not form if the viscosity is relatively small.

[Clinical experience of pain clinic in Kaohsiung Government Employees' Clinic Center].

UNLABELLED: This research was to analyze 1814 cases visited from January 1992 to December 1993 with respect to the characteristics and therapeutic effect of pain treatment in the pain clinic of Kaohsiung Government Employees' Clinic Center. The results were as follows: 1. Age level of patients ranged from 17 to 90 years old. The biggest group was of the old age group (956 cases, 52.7%). 2. Diagnostically, joint pain was the largest complain (602 cases, 33.2%). It was followed by spondylosis/spondylolithesis (324 cases, 17.9%) and myofascial pain syndrome (228 cases, 12.6%). There were 180 cases (9.9%) with two or more combined chronic pain syndrome. 3. Relationship between age and chronic pain: Old people were mostly suffered with osteoarthritis, spondylosis/spondylolithesis and post-herpetic neuralgia. Middle age people mainly had frozen shoulder, gouty arthritis and myofascial pain syndrome. Tendinitis and tension headache often occurred in young people. 4. Pre-treatment pain intensity: Most patients has Visual Analogue Scale of 7 to 8 (1622 cases, 89.4%). 5. THERAPEUTIC METHODS: Medication was mainly given to most of the patients. Some patients received nerve block (582 cases, 32.1%) and/or rehabilitation (389 cases, 21.4%). 6. Therapeutic effect was expressed by pain relief. Most patients felt moderate (708 cases, 39.0%) and almost complete pain relief (559 cases, 30.8%). CONCLUSION: Chronic pain could occurred in any age group. The kinds of chronic pain syndrome were prone to different age groups. Chronic pain patients could get good therapeutic effect if they cooperated with the doctor.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intravenous midazolam for sedation in epidural anesthesia].

30 cases receiving epidural anesthesia for lower extremities and abdominal surgery were selected in this study. Their physical status and average age were ASA I or II and 41 +/- 10.0 years old. Premedication included intramuscular injection of pethidine, atropine and promethazine. Epidural anesthesia was accomplished with 15 ml 2% lidocaine with epinephrine (1:80,000). After the stabilization of vital signs, the patients were put asleep by 0.1 mg/kg of midazolam intravenously. They were then evaluated by the sedative, cardiovascular, respiratory and recovery effects of intravenous midazolam in epidural anesthesia. The results were as follows: The patients receiving IV midazolam averagely fell asleep in 61.6 +/- 20.5 seconds and maintained asleep for 55.4 +/- 12.7 minutes. Pain on injection was not noted in these cases. Cardiovascular parameters revealed midazolam with general depression on systolic pressure (17.4 +/- 7.3%), diastolic pressure (13.4 +/- 8.4%), mean arterial pressure (12.7 +/- 7.0%), heart rate (10.9 +/- 7.2%), stroke volume (13.7 +/- 8.9%) and cardiac output (18.4 +/- 7.0%) respectively. The peak depression reached around 10 minutes after drug administration. Respiratory parameters dropped with SaO2 (1.1 +/- 1.6%) and respiratory rate (9.7 +/- 5.7%) and fell into trough after 5 minutes of drug administration. Although all the above parameters measured were statistically significant, they were of no clinical importance that required further management. No case had delirium, anxiety and vomiting in the recovery period. Conclusively, patients receiving epidural anesthesia with supplement of intravenous midazolam provides a good sedative effect. Clinically, there was less severe untowards reaction either in cardiovascular or respiratory systems. Smooth and stable recovery was also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

[The safety of geriatric anesthesia].

UNLABELLED: Perioperative abnormalities and complications were reviewed in 556 geriatric patients retrospectively to assess the safety of geriatric anesthesia. Preoperatively, the percentages of cases with cardiovascular and pulmonary abnormalities were 49.6% (276 cases) and 21.8% (121 cases) respectively. 77 percent of out patients (428 cases) were in the ASA class II physical status. The most common intraoperative complication was blood pressure instability and the incidence was noted to be of 34.8% (130 cases) with general anesthesia and of 15.8% (26 cases) with regional anesthesia. With general anesthesia, incidence for postoperative events such as non-fatal complications (i.e., sore throat and eye dryness), cardiovascular abnormalities and pulmonary disorders were found to be 39.0% (146 cases), 22.2% (83 cases) and 6.2% (23 cases) respectively. With regional anesthesia, the most common postoperative event was blood pressure instability (incidence: 21.2%, 35 cases). Total mortality rate of the first 15 postoperative days was 2.0% (11 cases). Mortality rate in elective and emergency surgery was 1.1% (5 cases) and 6.8% (6 cases) respectively. Causes of death were mainly related to illness deterioration (cancer and infection) or location of surgery. Death due to anesthetic mishap was nil in this study. IN CONCLUSION: Most geriatric patients had more than one system or one organ dysfunction before operation. Cardiovascular instability was the most common intraoperative complication. Postoperative mortality correlates closely with the preoperative ASA physical status. Mortality rate was significantly higher in emergency cases than in elective cases. A thorough pre-operative assessment and proper perioperative management are mandatory in geriatric anesthesia.

[The effect of nitrous oxide anesthesia combined with low dose alfentanil for minor surgery of short duration].

This study was conducted in 30 adult patients with ASA class I-II physical status who received minor operations. Anesthetic induction was achieved by injecting thiopental 4 mg/kg intravenously in addition to N2O/O2 (4L/2L) delivered via Ventri Mask, followed by alfentanil 7 micrograms/kg intravenously 3 min later. Maintenance of anesthesia was accomplished by N2O/O2 in conjunction with alfentanil 0.25-2.5 micrograms/kg/min, delivered intravenously by a syringe pump. Our result showed that in an operation of average duration around 40.2 +/- 10.5 min., the average dose of alfentanil used was 0.62 +/- 0.15 micrograms/kg/min. The respiration rate fell from 13.4 +/- 0.4 cpm to 8.4 +/- 1.1 cpm 2 min later following alfentanil injection, which was statistically significant. SaO2 fell from 97.9 +/- 0.4% to 94.0 +/- 0.8% 3 min after alfentanil injection, which was statistically significant. End-tidal carbon dioxide partial pressure elevated from 39.4 +/- 0.6 mmHg to a peak of 45.3 +/- 1.2 mmHg 5 min after alfentanil injection which was also statistically significant. Temporary apnea was noted in 3 cases, but they all resumed spontaneous respiration after a short period of assisted ventilation. Changes in systolic and diastolic pressure during anesthesia were not marked. Pulse rate was noted to decrease from 80.3 +/- 2.7 bpm to 70.5 +/- 2.0 bpm 1 min after alfentanil injection, which was statistically significant (p less than 0.05). After discontinuation of N2O, the time required to regain the ability to follow orders of "open your eyes," "show your thumb" and "say your name" in sequence was 72.5 +/- 10.6s, 88.2 +/- 11.6s, 128.1 +/- 23.0s, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Low-flow anesthesia].

Low-flow anesthesia provides benefits of ecologic advantages, reduction of pollution of operating room, increased economy and prevention of airway dessication. It is worthy to gain popularity of application. In this review article, certain aspects of low-flow anesthesia are included: 1) how to avoid hypoxemia, 2) how to prevent carbon dioxide retention, 3) how to use Lin's method in calculating the metered concentration of inhalational anesthetics during maintenance period, 4) how the time constant to affect the time to surgical level of anesthesia, and 5) the indications of low-flow anesthesia for surgery. Finally, clinical experience in low-flow anesthesia will be discussed in terms of halothane, enflurane or isoflurane with or without nitrous oxide.

[Intravenous propofol as a supplement in epidural anesthesia].

Under study were thirty patients of ASA class I-II scheduled for lower abdominal and lower extremities surgery. Premedication included intramuscular injection of pethidine, atropine and prochlorperazine. Epidural anesthesia was accomplished with 12-15 ml 2% lidocaine with epinephrine (1:80,000). Thirty minutes later, when blood pressure returned to control value, patients were put to sleep by 2 mg/kg propofol and the sleep was maintained with continuous infusion of propofol at a rate of 6 mg/kg/h. Infusion rate was adjusted when necessary. Patients breathed room air spontaneously through the whole course of anesthesia. The results showed that all patients fell to sleep within 28.3 +/- 2.7 s after intravenous injection of propofol 2 mg/kg. Sleeping dose was satisfactorily achieved using a mean infusion rate of 6.1 +/- 1.7 mg/kg/h. The mean time from the end of the infusion of propofol to opening of the eyes on command and telling the correct date of birth were 7.9 +/- 2.8 min and 9.9 +/- 3.8 min respectively. Two minutes after injection, there were significant decrease in systolic pressure, diastolic pressure, cardiac output, and stroke volume with a mean of 17.9 +/- 3.8%, 18.8 +/- 3.3%, 7.6 +/- 0.5% and 11.1 +/- 1.9% respectively. Two patients (7%) developed apnea after 2 mg/kg propofol which was considered to be the most serious side effect. Propofol infusion had to be stopped in 13% patients due to a 30% fall of arterial blood pressure during maintenance. In the recovery stage, no other complications were noted except one patient who felt dizziness. Propofol, used as the supplementary sedative, provides satisfactory result for surgery under epidural anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical study of awake fiberoptic nasotracheal intubation for difficult opening mouth patients].

The intubation technique for those surgical patients considered to be difficult intubation were classically managed by blind nasotracheal intubation, tracheostomy and so forth. These procedures are rather invasive and resulted in post-operative complications. 30 adult patients of ASA class II-III with difficulty in intubation were chosen to receive awake fiberoptic nasotracheal intubation. Our aim of study is to evaluate the change of blood pressure, heart rate and SaO2 of these patients at 4 stages: I) preanesthesia II) transtracheal local block III) during intubation IV) post-intubation. As a result, there were no significant difference in comparing the parameters among these 4 stages. Additionally, fiberoptic guiding provide a direct vision on the way of intubation, enhance the successful rate of difficult intubation and minimize further trauma and discomfort to the patients. Therefore fiberoptic intubation may suitable in patients with difficult intubation.

[Propofol intravenous anesthesia for intra-arterial catheterization in cancer patients].

Thirty cancer patients scheduled for intra-arterial catheterization for chemotherapy were premedicated with pethidine 1 mg/kg atropine 0.807 mg/kg and prochlorperazine 5 mg intramuscularly. Anesthesia was induced with 2 mg/kg propofol and maintained with continuous infusion of propofol at a rate of 12 mg/kg/h. Patients breathed room-air spontaneously through the whole course of anesthesia. Anesthesia was induced with 2 mg/kg propofol in all patients, then maintained successfully by using a mean infusion rate of 12.13 +/- 0.43 mg/kg/h propofol. They lost consciousness within 29.60 +/- 5.50 second. Two minutes after induction, there were significantly decreased in systolic pressure, diastolic pressure, stroke volume and cardiac output but heart rate did not change significantly. Blood pressure and cardiac output remained stable but lower than pre-anesthetic values during the rest of the anesthetic course. Arterial blood gas analysis confirmed the respiratory depression. Two minutes after induction, there were significantly decreased in PaO2, SaO2 and pH were noted. PaCO2 was increased significantly. Recovery from the anesthesia was rapid and uneventful. The average time required for the patients to sustain eye-opening and to answer questions were 9.20 +/- 1.79 min and 10.73 +/- 1.87 min respectively after discontinuing propofol injection. Transient restlessness occurred in one patient. No other post-operative complications were noted.