Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Magnitude of Mycobacterium tuberculosis transmission among household and non-household contacts of TB patients.

The household and non-household contacts of patients with tuberculosis (TB) face varying degrees of risk of infection by Mycobacterium tuberculosis. To quantify new infection and to determine the risk factors associated with new infection among named contacts in San Francisco, CA, USA. We performed a cohort study in patients with culture-positive pulmonary TB. We analyzed patient, contact, environmental and bacterial characteristics. Of the 2422 contacts named by 256 patients, 149 (6.2%) had new infection due to recent transmission from 79 (30.9%) patients. Of the 149 new infections, 87 (58.4%) occurred among household contacts and 62 (41.6%) among non-household contacts. Numerous acid-fast bacilli in sputum (odds ratio [OR] 2.64, 95%CI 1.32-5.25) and contacts being named by more than one patient (OR 2.90, 95%CI 1.23-6.85) were associated with new infection among household contacts. Being older than 50 years (OR 1.93, 95%CI 1.09-3.41) and an Asian/Pacific Islander (OR 3.09, 95%CI 1.50-6.37) were associated with new infection among non-household contacts. Fewer than one third of patients caused new infection to his/her contacts. A substantial proportion of transmission resulting in new infection occurred outside of the household. The risk factors for infection among household and non-household contacts are different and should be considered when prioritizing control interventions. .

Testosterone effects on pain and brain activation patterns.

BACKGROUND: This study investigated whether pain and pain-related unpleasantness ratings were altered by blood testosterone levels. We also investigated whether activation of brain regions that represent pain intensity [primary somatosensory cortex (S1)] and pain-related unpleasantness [perigenual ACC (pACC) and orbitofrontal cortex (OFC)] were affected by blood testosterone levels. METHODS: Twenty-six healthy men were recruited. Blood testosterone levels were measured before fMRI scanning. The participants were classified into two groups (high vs. low testosterone) according to their blood testosterone level (each group n = 13). The middle finger was immersed in a 50°C water bath (50°C, 30 s, five times) to induce identical noxious stimulation in all participants. RESULTS: The low testosterone group showed statistically significantly higher pain (P = 0.047), unpleasantness (P = 0.047), anxiety (P = 0.015), and fear ratings (P = 0.01) than the high testosterone group. Fear rating increased as pain rating rose and as testosterone level decreased (P < 0.001). When participants received noxious stimulation, the pACC and OFC were more highly activated in the low testosterone group compared to the high testosterone group. Activation of S1, a region related to pain intensity, did not differ between both groups. CONCLUSION: Compared to the high testosterone group, the low testosterone group had significant activation in the pACC and OFC, regions that represent pain-related unpleasantness, but not in S1 that represents pain intensity, leading to higher pain ratings. These findings emphasize the importance of considering the effects of testosterone levels when treating patients.

Brain mechanisms of pain relief by transcutaneous electrical nerve stimulation: A functional magnetic resonance imaging study.

BACKGROUND: Although the exact mechanism of TENS pain relief is unknown, it is believed that TENS impulses interrupt nociceptive signals at the dorsal horn of the spinal cord. AIMS: To evaluate the hypotheses that during pain caused by noxious stimuli, brain responses, temporal summation and brain functional connectivity are modulated by TENS, and that mechanisms of pain relief by TENS differ between men and women. METHODS: During fMRI scanning, the same noxious stimuli were delivered to each participant in pain-only and pain+TENS conditions. In the pain-only condition, noxious stimuli were presented without TENS. In the pain+TENS condition, participants received noxious stimuli and TENS concurrently. Participants were initially presented with TENS at an intensity that was just below that causing discomfort. TENS intensity was presented in a step-wise fashion to prevent temporal summation from repetitive noxious stimuli. RESULTS: Pain and unpleasantness ratings were significantly higher in the pain-only than the pain+TENS condition. With non-painful TENS, primary and secondary somatosensory and parietal cortices were activated, and temporal summation from repetitive noxious stimuli was prevented. Periaqueductal gray (PAG) and lateral prefrontal cortex functional connectivity was increased by TENS, and modulated by testosterone and cortisol. Women reported greater pain during TENS than men, and showed greater activation in the temporoparietal junction cortex and increased PAG functional connectivity with the orbitofrontal cortex. CONCLUSION: TENS led to pain reduction, probably due to activation of the descending pain-inhibitory pathway, indicating that this TENS method may be applied in clinical practice.

Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation.

BACKGROUND: We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. METHODS: During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. RESULTS: Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. CONCLUSION: When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last.

Reduced sensitivity of the QuantiFERON(®) test in diabetic patients with smear-negative tuberculosis.

SETTING: Immunosuppressive conditions have been associated with low sensitivity of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for the diagnosis of tuberculosis (TB). However, no systematic analysis of patient and bacterial characteristics has been performed before. OBJECTIVE: To determine the sensitivity and the risk factors for false-negative QuantiFERON(®)-TB (QFT) assay and TST in TB patients. DESIGN: We performed a retrospective analysis of data collected in a community-based study of TB in San Francisco, CA, USA. We included 300 TB patients who underwent QFT and TST. RESULTS: The risk factors for false-negative QFT were human immunodeficiency virus infection and the use of QuantiFERON(®)-TB Gold. In patients with sputum smear-negative TB, diabetes mellitus (DM) was associated with false-negative QFT (OR 2.85, 95%CI 1.02-7.97, P = 0.045). TST sensitivity was higher than QFT sensitivity in DM patients (OR 9.46, 95%CI 2.53-35.3). CONCLUSIONS: In San Francisco, QFT sensitivity was lower than that of TST, especially in patients with DM. Stratified analysis by sputum smear results showed that this association was specific to smear-negative TB. In contrast, TST was not affected by the presence of DM.

Modulation of pain sensation by stress-related testosterone and cortisol.

Stress increases cortisol and decreases testosterone. It is not known whether pain is affected by stress-related testosterone. Therefore, we investigated whether stress can affect pain perception by decreasing testosterone and increasing cortisol. Pain thresholds, pain and anxiety ratings and salivary testosterone and cortisol levels were measured in 46 healthy men during resting and stressful conditions. Pain was induced by electrical stimulation. Stress was induced by having participants perform a medical test. Stress significantly increased anxiety ratings and salivary cortisol levels, but decreased salivary testosterone levels. Stress also increased pain ratings and decreased pain thresholds. During stress, cortisol levels were negatively correlated with pain thresholds and testosterone levels were positively correlated with pain thresholds. Results indicated that testosterone can decrease and cortisol can increase pain induced by electrical stimulation, suggesting that acute clinical pain may be relieved by controlling stress and managing consequent stress-related testosterone and cortisol.

Paradoxical response in HIV-negative patients with pleural tuberculosis: a retrospective multicentre study.

OBJECTIVE: To evaluate the incidence, clinical characteristics and predicting factors for the development of paradoxical response in human immunodeficiency virus negative patients with isolated pleural tuberculosis (TB). DESIGN: A multicentre, retrospective cohort study including 458 patients who were diagnosed and treated with isolated pleural TB between March 2005 and February 2010. RESULTS: Paradoxical response developed in 72 patients (16%) with isolated pleural TB. The mean time to development of paradoxical response was 8.8 ± 6.4 weeks after initiation of anti-tuberculosis treatment. The main presentation of paradoxical response was aggravation of pre-existing pleural effusion in 58 patients (81%). However, the majority of the patients who developed paradoxical response had no associated symptoms (n = 49, 68%). In multiple logistic regression analysis, development of paradoxical response was independently associated with the proportion of eosinophils (adjusted OR 1.293, 95%CI 1.077-1.553) and protein concentrations (adjusted OR 0.590, 95%CI 0.397-0.878) in the pleural fluid at the time of diagnosis. CONCLUSION: Paradoxical response developed in 16% of the patients approximately 2 months after initiation of anti-tuberculosis treatment, presenting with aggravation of pre-existing pleural effusion. Development of paradoxical response was associated with the proportion of eosinophils and protein concentrations in the pleural fluid at the time of diagnosis.

The effect of diabetic control status on the clinical features of pulmonary tuberculosis.

The aim of this study was to determine whether control status of diabetes mellitus influences clinical and radiographic manifestations and treatment responses in patients with tuberculosis (TB). The medical records of 492 patients who started anti-TB medication between January 2005 and December 2009 were retrospectively reviewed. Diabetes was diagnosed in 124 patients (25.2%). Of these, 74 (59.7%) were uncontrolled (HbA1C≥7.0), 25 (20.2%) were controlled (HbA1C<7.0), and HbA1C levels were not assessed in the remaining 25 (20.2%). There were no differences in clinical symptoms between diabetics and non-diabetics, regardless of diabetes control status. There were also no differences in radiographic findings or AFB results between controlled diabetics and non-diabetics. However, uncontrolled diabetics had more cavitary lesions (p=0.008) and higher positive smear rates (p<0.001) compared with non-diabetics. After adjustment for age, cavities and positive smears before initiation of treatment, uncontrolled diabetes was a significant risk factor for a positive sputum culture at 2 months (odds ratio, 4.316; 95% CI, 1.306-14.267; p=0.017). Uncontrolled diabetics seem to have more cavities, higher positive smear rates and lack of culture conversion after two months of therapy. Therefore, TB patients with uncontrolled diabetes should be carefully managed and treated.

Clinical characteristics and outcomes of H1N1-associated pneumonia among adults in South Korea.

BACKGROUND: Pneumonia has been reported to be the most life-threatening complication of influenza virus infection. OBJECTIVE: to describe clinical characteristics and determine risk factors for death among patients with H1N1-associated pneumonia. DESIGN: A retrospective cohort study included all adult patients diagnosed and treated with H1N1-associated pneumonia in 14 participating institutions between 1 May 2009 and 28 February 2010 in South Korea. Clinical outcomes were summarised and predictors for death evaluated through univariate and multivariate analysis. RESULTS: A total of 269 adult patients with H1N1-associated pneumonia were diagnosed and treated. Hospital visits or admissions peaked in November 2009, coinciding with the peak in the 2009 H1N1 epidemic in South Korea. The patients' median age was 48 years; 143 were male. Most (n = 266, 98.9%) were admitted for treatment: 97 (36.1%) required intensive care and 28 (10.4%) needed mechanical ventilation. Despite the use of antiviral and antibacterial agents, 19 patients (7.1%) died. Risk factors predictive of death included presence of malignancy (aOR 12.0, 95%CI 2.8-51.5), and pneumonia severity index (PSI) score (aOR 1.03, 95%CI 1.01-1.04). CONCLUSION: Deaths among adult patients with H1N1-associated pneumonia were not rare. Clinicians should be aware of the possibility of a poor prognosis among H1N1-associated pneumonia patients with underlying malignancy or high PSI score.

Spitz naevus is rare in Korea.

BACKGROUND: Spitz naevi have not been widely studied in Asians. AIM: To compare the epidemiology and clinicopathological features of Spitz naevi in Koreans with lesions in western countries. METHODS: In total, 80 Spitz naevi in 77 patients diagnosed over 10 years at 17 university hospitals in Korea were analysed. RESULTS: The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most patients (75%) the Spitz naevi had been present for > 6 months. The size of the lesion was relatively large. Histologically, most of the lesions (54%) were the dermal type and pigmentation was common (49% of lesions). Immunohistochemical study found that all of the 34 lesions were positive for S-100 protein but only 14 (47%) were positive for HMB-45. CONCLUSION: Spitz naevus is rare in Korea. The lesions were more commonly larger, pigmented, and of the dermal type than reported in western countries.

Effects of cocaine place conditioning, chronic escalating-dose "binge" pattern cocaine administration and acute withdrawal on orexin/hypocretin and preprodynorphin gene expressions in lateral hypothalamus of Fischer and Sprague-Dawley rats.

Recent evidence suggests an important role for hypothalamic orexins/hypocretins in modulation of drug reward and addiction-like behaviors in rodents. Our recent study has shown that the aversive state of arousal during acute morphine withdrawal is associated with increased orexin gene expression in lateral hypothalamus (LH) of Fischer 344 (F344) inbred rats, with no change in the expression of preprodynorphin (ppDyn), a gene co-expressed with LH orexin. Therefore, we determined whether orexin and ppDyn mRNA levels in LH or medial hypothalamus (including perifornical and dorsomedial areas) of F344 or Sprague-Dawley (SD) outbred rats, are altered following: 1) cocaine (10 mg/kg, i.p.) conditioned place preference (CPP); 2) chronic (14 days) cocaine exposure using both "binge" pattern administration in steady-dose (45 mg/kg/day) and escalating-dose (45-90 mg/kg/day) regimens; and 3) acute (1 day) and chronic (14 days) withdrawal from cocaine with opioid receptor antagonist naloxone treatment (1 mg/kg). We found that orexin mRNA levels were decreased after cocaine place conditioning in the LH of SD rats. A decreased LH orexin mRNA level was also observed after chronic escalating-dose cocaine (but not CPP pattern regimen without conditioning, or steady-dose regimen) in both strains. In F344 rats only, acute withdrawal from chronic escalating-dose cocaine administration resulted in increases in both LH orexin and ppDyn mRNA levels, which were unaltered by naloxone or after chronic withdrawal. Our results suggest that (1) alteration of LH orexin gene expression is region-specific after cocaine place conditioning in SD rats and dose-dependent after chronic exposure in both strains; and (2) increased LH orexin and ppDyn gene expressions in F344 rats may contribute to negative affective states in cocaine withdrawal.

Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.

The role of bronchoscopic management in post-tuberculosis tracheobronchial stenosis is not well defined. To investigate the role of bronchoscopic intervention, including silicone stenting, in the management of post-tuberculosis tracheobronchial stenosis, the current retrospective study was conducted at a tertiary referral hospital. Under rigid bronchoscopy, 80 patients underwent ballooning, neodymium-yttrium aluminium garnet laser resection and/or bougienation as first-line methods of airway dilatation between January 2000 and December 2003 inclusive, and were followed for a median of 41 months. Silicone stents were required in 75 out of 80 (94%) patients to maintain airway patency. Bronchoscopic intervention provided immediate symptomatic relief and improved lung function in 88% of the patients. After airway stabilisation, stents were removed successfully in 49 out of 75 (65%) patients at a median of 14 months post-insertion. Three patients out of 75 (4%) eventually underwent surgical management. Acute complications included: excessive bleeding (n = 1); pneumothorax (n = 5); and pneumomediastinum without mortality (n = 2). Stent-related late complications, such as migration (51%), granuloma formation (49%), mucostasis (19%) and re-stenosis (40%), were controllable during a median follow-up of 41 months. In conclusion, bronchoscopic intervention, including silicone stenting, could be a useful and safe method for treating post-tuberculosis tracheobronchial stenosis.