Jayanton Patumanond

Focal Modulation of the Primary Motor Cortex in Fibromyalgia Using 4! 1-Ring High-Definition Transcranial Direct Current Stimulation (HD-tDCS): Immediate and Delayed Analgesic Effects of Cathodal and Anodal Stimulation

UNLABELLED Fibromyalgia is a prevalent chronic pain syndrome characterized by altered pain and sensory processing in the central nervous system, which is often refractory to multiple therapeutic approaches. Given previous evidence supporting analgesic properties of noninvasive brain stimulation techniques in this condition, this study examined the effects of a novel, more focal method of transcranial direct current stimulation (tDCS), using the 4×1-ring configuration of high-definition (HD)-tDCS, on overall perceived pain in fibromyalgia patients. In this patient- and assessor-blind, sham-controlled, crossover trial, 18 patients were randomized to undergo single 20-minute sessions of anodal, cathodal, and sham HD-tDCS at 2.0 mA in a counterbalanced fashion. The center electrode was positioned over the left primary motor cortex. Pain scales and sensory testing were assessed before and after each intervention. A finite element method brain model was generated to predict electric field distribution. We found that both active stimulation conditions led to significant reduction in overall perceived pain as compared to sham. This effect occurred immediately after cathodal HD-tDCS and was evident for both anodal and cathodal HD-tDCS 30 minutes after stimulation. Furthermore, active anodal stimulation induced a significant bilateral increase in mechanical detection thresholds. These interventions proved well tolerated in our patient population. PERSPECTIVE 4×1-ring HD-tDCS, a novel noninvasive brain stimulation technique capable of more focal and targeted stimulation, provides significant reduction in overall perceived pain in fibromyalgia patients as compared to sham stimulation, irrespective of current polarity. This technique may have other applications in research and clinical settings, which should be further explored.

Necrotizing fasciitis: risk factors of mortality.

Background Necrotizing fasciitis (NF) is a serious infection of skin and soft tissues that rapidly progresses along the deep fascia. It becomes a fatal soft tissue infection with high mortality rate if treatment is delayed. Early diagnosis for emergency surgical debridement and broad-spectrum antibiotic therapy were the optimal treatments to reduce the mortality rate of NF. Objective The aim of this study was to identify risk factors that increased the mortality rate in patients with NF under routine clinical practices. Methods A retrospective cohort study was performed at three general hospitals located in northern Thailand. All medical records of patients with surgically confirmed NF treated between January 2009 and December 2012 were reviewed. Clinical predictors for mortality were analyzed using multivariable risk regression analysis. Results Of a total of 1,504 patients with a diagnosis of NF, 19.3% (n=290) died in hospital and 80.7% (n=1,214) survived. From multivariable analysis, being female (risk ratio [RR] =1.37, 95% confidence interval [CI] =1.01–1.84); age >60 (RR=1.39, 95% CI =1.25–1.53); having chronic heart disease (RR=1.64, 95% CI=1.18–2.28), cirrhosis (RR =2.36, 95% CI=1.70–3.27), skin necrosis (RR =1.22, 95% CI=1.15–1.28), pulse rate >130/min (RR =2.26, 95% CI=1.79–2.85), systolic BP <90 mmHg (RR =2.05, 95% CI =1.44–2.91), and serum creatinine ≥1.6 mg/dL (RR=3.06, 95% CI=2.08–4.50) were risk factors for mortality. Conclusion Prognostic factors for mortality in NF patients included being female; age >60; or having chronic heart disease, cirrhosis, skin necrosis, pulse rate >130/min, systolic BP <90 mmHg, and serum creatinine ≥1.6 mg/dL. Thus, disease progression to mortality may occur in such patients presenting one of these risk factors. Further examination or close monitoring for systemic involvement may be advantageous to reduce morbidity and mortality.

Factors related to suicide attempts among individuals with major depressive disorder

Background Major depressive disorder (MDD) is the leading cause of suicidal behaviors. Risk related to suicide attempts among individuals with MDD remains uninvestigated in upper northern Thailand, where the completed suicide rate is the highest in the nation. Objective To examine risk related to suicide attempts among individuals with MDD. Methods Individuals diagnosed with MDD using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), codes F32.x and F33.x, seeking care at Suanprung Psychiatric Hospital between October 2006 and May 2009 were eligible. All individuals with MDD admitted due to suicide attempts were defined as cases (n = 186), and four controls per case were selected from those who did not attempt suicide on the same day or within a week of case selection (n = 914). Their medical charts were reviewed for sociodemographic and clinical factors influencing suicide attempts using multivariable logistic regression analysis. Results Factors related to suicide attempts were stressful life events (adjusted odds ratio [OR], 2.32; 95% confidence interval [CI]: 1.27–4.24), alcohol use (adjusted OR, 2.08; 95% CI: 1.29–3.34), intermittent or poor psychiatric medications adherence (adjusted OR, 2.25; 95% CI: 1.44–3.51), up to two previous suicide attempts (adjusted OR, 3.64; 95% CI: 2.32–5.71), more than two previous suicide attempts (adjusted OR, 11.47; 95% CI: 5.73–22.95), and prescribed antipsychotics (adjusted OR, 3.84; 95% CI: 2.48–5.95). Risk factors that were inversely related to suicide attempts were increasing years of MDD treatment; one to five years (adjusted OR, 0.22; 95% CI: 0.11–0.44), over five years (adjusted OR, 0.44; 95% CI: 0.23–0.86), and antidepressant prescribed (norepinephrine [NE] and/or serotonin reuptake inhibitors [SRIs], adjusted OR, 0.28; 95% CI: 0.10–0.78). The final model explained 85.8% probability of suicide attempts. Conclusion Seven key factors suggested from this study may facilitate clinicians to identify individuals with MDD at risk of suicide attempt and provide them close monitoring, timely assessment, and intensive treatments.

A randomized controlled trial of pentazocine versus ondansetron for the treatment of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery.

BACKGROUND: Ondansetron is effective for the treatment of intrathecal morphine-induced pruritus. There is evidence that &kgr;-opioid receptor agonists have antipruritic activity. Pentazocine is an agonist of &kgr;-opioid receptors and partial agonist at &mgr;-opioid receptors. We therefore performed a randomized, double-blind trial to compare the efficacy of pentazocine and ondansetron for the treatment of pruritus associated with intrathecal injection of morphine in patients undergoing cesarean delivery. METHODS: Two hundred eight parturients who developed moderate to severe pruritus after the administration of intrathecal morphine were randomly allocated to 2 groups: IV pentazocine 15 mg (n = 104) and IV ondansetron 4 mg (n = 104). The successful treatment of pruritus (no or mild pruritus) and other adverse effects were determined 15 min after study drug administration, and patients were observed for recurrence of pruritus for 4 h. RESULTS: The treatment success rate at 15 min was higher in the pentazocine group (96.1%) than in the ondansetron group (80.8%) (95% confidence interval of difference: 7.0%, 23.8%; P = 0.001). The recurrence rate of moderate to severe pruritus within 4 h after treatment in the pentazocine group (12.0%) was lower than in the ondansetron group (32.1%) (P = 0.001). There were no significant differences between groups in nausea/vomiting, sedation, shivering, pain scores, and pain at injection site. No respiratory depression was observed. CONCLUSIONS: Pentazocine 15 mg is superior to ondansetron 4 mg for the treatment of intrathecal morphine-induced pruritus and has a lower recurrence rate. The side effects after treatment are mild.

The prognostic value of ERCC1 and RRM1 gene expression in completely resected non-small cell lung cancer: tumor recurrence and overall survival

Background The roles of excision repair cross-complementing group 1 gene (ERCC1) expression and ribonucleotide reductase subunit M1 gene (RRM1) expression in completely resected non-small cell lung cancer (NSCLC) are still debatable. Previous studies have shown that both genes affected the overall survival and outcomes of patients who received platinum-based chemotherapy; however, some studies did not show this correlation. The aim of this study was to evaluate the prognostic values of ERCC1 and RRM1 gene expression in predicting tumor recurrence and overall survival in patients with completely resected NSCLC who received adjuvant chemotherapy and in those who did not. Patients and methods A retrospective cohort study was conducted in 247 patients with completely resected NSCLC. All patients had been treated with anatomic resection (lobectomy or pneumonectomy) with systematic mediastinal lymphadenectomy between January 2002 and December 2011 at Chiang Mai University Hospital, Chiang Mai, Thailand. They were divided into two groups: recurrence and no recurrence. Protein expression of ERCC1 and RRM1 was determined by immunohistochemistry. Correlations between clinicopathologic variables, including ERCC1 and RRM1 expression and tumor recurrence, were analyzed. Univariate and multivariate Cox proportional hazards regression analysis stratified by nodal involvement, tumor staging, intratumoral blood vessel invasion, intratumoral lymphatic invasion, and tumor necrosis was used to identify the prognostic roles of ERCC1 and RRM1. Results ERCC1 and RRM1 expression did not demonstrate prognostic value for tumor recurrence and overall survival in patients with completely resected NSCLC. In patients who did not receive adjuvant chemotherapy treatment, those with high ERCC1 and high RRM1 expression seemed to have greater potential for tumor recurrence and shorter overall survival than did those who had low ERCC1 and low RRM1 (hazard ratio [HR] =1.7, 95% confidence interval [CI] =0.6–4.3, P=0.292 and HR =1.6, 95% CI =0.5–4.5, P=0.411, respectively). In contrast, in patients who received adjuvant chemotherapy treatment, those with high ERCC1 and high RRM1 expression seemed to have benefited from adjuvant chemotherapy and showed good overall survival compared with those who had low ERCC1 and low RRM1 (HR =0.8, 95% CI = 0.4–1.8, P=0.612 and HR = 0.4, 95% CI = 0.1–2.4, P=0.325, respectively). Subgroup analysis in patients whose first-line metastatic chemotherapy failed demonstrated that ERCC1 expression and RRM1 expression were not prognostic factors for tumor recurrence and overall survival; however, patients who had high ERCC1 and high RRM1 expression seemed to have benefited from first-line chemotherapy treatment (HR =0.7, 95% CI =0.3–1.8, P=0.458). Conclusion ERCC1 expression and RRM1 expression were not prognostic of tumor recurrence and overall survival in patients with completely resected NSCLC, either with or without adjuvant chemotherapy. Prospective studies that include a larger number of patients are needed for definite conclusions.

Incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients

Background The incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients remain uninvestigated in Thailand. Objective To determine incidence and risk factors of suicide reattempts within 1 year after psychiatric hospital discharge in mood disorder patients. Methods A retrospective cohort study was conducted by reviewing medical charts at Suanprung Psychiatric Hospital, Chiang Mai, Thailand. Mood disorder patients, diagnosed with the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes F31.x, F32.x, and F33.x, who were admitted owing to suicide attempts between October 2006 and May 2009 were eligible. The influence of sociodemographic and clinical risk factors on suicide reattempts was investigated using Cox’s proportional-hazards regression analysis. Results Of 235 eligible mood disorder patients, 36 (15.3%) reattempted suicide (median 109.5 days, range 1–322), seven (3.0%) completed suicide (median 90 days, range 5–185), and 192 (84.2%) neither reattempted nor completed suicide during follow-up. Of all nonfatal suicide reattempts, 14 patients (38.9%) did so within 90 days. Among suicide completers, one (14.3%) did so 5 days after discharge, and four (57.1%) did so within 90 days. The following three risk factors explained 73.3% of the probability of suicide reattempts: over two previous suicide attempts before the index admission (adjusted hazard ratio [HR] 2.48; 95% confidence interval [CI] 1.07–5.76), being concomitantly prescribed typical and atypical antipsychotics (adjusted HR 4.79; 95% CI 1.39–16.52) and antidepressants, and taking a selective serotonin reuptake inhibitor alone (adjusted HR 5.08; 95% CI 1.14–22.75) or concomitantly with norepinephrine and/or serotonin reuptake inhibitors (adjusted HR 6.18; 95% CI 1.13–33.65). Conclusion Approximately 40% of suicide reattempts in mood disorder patients occurred within 90 days after psychiatric hospital discharge. For mood disorders and when there have been over two previous suicide attempts, prescribed antipsychotics or antidepressants may help predict suicide reattempts.

Necrotizing fasciitis: epidemiology and clinical predictors for amputation

Background Necrotizing fasciitis, a relatively uncommon infection involving the skin, subcutaneous tissue, and fascia, is a rapidly progressive soft tissue infection and a medical and surgical urgency. Delayed debridement, with subsequent huge soft tissue loss is associated with loss of limb and infection and is the most common cause of mortality. The purpose of this work is to describe the epidemiology of necrotizing fasciitis and to identify the clinical characteristics that may be used to predict amputation in routine clinical practice. Methods Retrospective cohort study data were collected from three general hospitals located in the Chiang Rai, Kamphaeng Phet, and Phayao provinces in northern Thailand. Epidemiologic data for all patients with a surgically confirmed diagnosis of necrotizing fasciitis between 2009 and 2012 were collected. Medical records and reviews were retrieved from inpatient records, laboratory reports, and registers. Clinical predictors for amputation were analyzed by multivariable risk regression. Results A total of 1,507 patients with a diagnosis of necrotizing fasciitis were classified as being with amputation (n=127, 8.4%) and without amputation (n=1,380, 91.6%). The most common causative Gram-positive and Gram-negative pathogens were Streptococcus pyogenes (33.3% in the amputation group and 40.8% in the non-amputation group) and Escherichia coli (25% in the amputation group and 17.1% in the non-amputation group). Predictive factors for amputation included gangrene (risk ratio [RR] 4.77, 95% confidence interval [CI] 2.70–8.44), diabetes mellitus (RR 3.08, 95% CI 1.98–4.78), skin necrosis (RR 2.83, 95% CI 2.52–3.18), soft tissue swelling (RR 1.76, 95% CI 1.24–2.49), and serum creatinine values ≥1.6 mg/dL on admission (RR 1.71, 95% CI 1.38–2.12). All data were analyzed using the multivariable risk regression generalized linear model. Conclusion The most causative pathogens were S. pyogenes and E. coli. Clinical predictors for amputation in patients with necrotizing fasciitis included having diabetes mellitus, soft tissue swelling, skin necrosis, gangrene, and serum creatinine values ≥1.6 mg/dL on admission. Thus, patients with any of these predictors should be monitored closely for progression and receive early aggressive treatment to avoid limb loss.

Effect of angiotensin II receptor blockers on insulin resistance in maintenance haemodialysis patients

Aim:  Insulin resistance is a predictor of cardiovascular mortality in patients with end‐stage renal disease. Although some clinical studies demonstrated that angiotensin II receptor blockers (ARB) improve insulin action in hypertensive patients, the role of ARB among patients with maintenance haemodialysis (MHD) remains controversial. The aim was to evaluate the effect of the ARB on insulin resistance in patients with MHD.

Dengue Hemorrhagic Fever, Uttaradit, Thailand

To the Editor: Dengue hemorrhagic fever (DHF) has been recognized as a disease of young children in the past. Three decades ago most reported case-patients in Thailand were 3–6 years of age (1). Increasing evidence shows that the age group most affected is changing (2). We report evidence that in Uttaradit, Thailand, the predominant age of those who acquire DHF has increased by at least 2 years during the 1990s. Uttaradit is a province in the northern part of Thailand. DHF is endemic in Uttaradit, as it is in most parts of the country. Between 1992 and 2001, three major outbreaks of DHF occurred, in 1993, 1998, and 2001. The number of DHF cases reported to the Provincial Health Office from January 1992 to December 2001 (classified by age groups) was used as the estimated annual DHF incidence. Case definition and categorization followed the International Statistical Classification of Diseases and Related Health Problems (ICD-10). DHF categories reported in this study included both DHF without shock and the dengue shock syndrome (the number of cases and deaths combined). Dengue fever, a milder disease manifestation, was not included. The age distribution of DHF cases showed that, in the 1993 epidemic, children 5–9 years of age had the largest proportion of cases, whereas in 2001, the peak age of those infected was 10–14 years. The transitional stage (mean age 11.3 years) was observed in 1998. During the observed period, the annual mean age of DHF case-patients ranged from 8.4 to 15.1 years. Despite some fluctuation, the mean age of DHF case-patients was 10 years. The incidence of DHF in children <4 years of age decreased from 586.0/100,000 in the 1993 epidemic to 197.5/100,000 in 2001. The incidence in children 5–9 years of age also decreased from 1,330.3/100,000 to 676.6/100,000 in the corresponding years. While the incidence in children 10–14 years of age remained unchanged, the incidence in those 15–24 years of age increased from 122.8/100,000 to 323.5/100,000, and from 20.0 to 52.6 per 100,000, a more than twofold increase. Our results clearly showed that the mean age of DHF cases increased from 10.0 years in the 1993 epidemic to 11.3 years in 1998 and to 13.2 years in 2001, as a consequence of a decrease in the incidence among children <9 years, and an increase in the incidence among the older age groups. This finding was similar to what had been observed earlier in Singapore and Indonesia (2,3). Some researchers have found that when the average number of annual dengue infections declines, the chance of persons acquiring dengue infections declines, resulting in delays in the age when a person has experienced the first, then second, dengue infection (4). However, in Uttaradit, as well as in other parts of Thailand, dengue infection is endemic, with large outbreaks occurring at 2- to 3-year intervals: later epidemics have also shown an increase in the overall incidence rates. Thus, this explanation is unlikely to be the reason for a shift in the age distribution of DHF in Uttaradit. We reviewed information that indicated that the shift in age predominance could be caused by the changes in places of transmission. Among these was the study in Singapore, which proposed that an effective mosquito-control program in households had resulted in changes in which age group had the largest number of DHF cases (5). A significant (p 6 years of age coincided with the start of formal schooling. The likelihood of dengue infection increased with time spent away from home, suggesting that the location where dengue was acquired may have changed (5). The recent study in Thailand also suggested that, although dengue infection may be transmitted in the home environment, transmission within schools may also be important (6). The changing of the population age structure also explained the age shifting phenomenon in some studies (7). In Uttaradit, however, changes in the age structure of the population were small from 1992 to 2001. The intervening effect of vaccination against Japanese encephalitis virus, a different but related flavivirus, could also explain why the mean age for most cases of DHF increased. Cross-reaction between dengue virus and Japanese encephalitis virus is well established (8). Vaccination against Japanese encephalitis virus may temporarily protect persons, primarily young children, against dengue infection or at least reduce its severity, resulting in a decline in the observed incidence. The cohort of these vaccine recipients were then exposed to dengue infection later in life and exhibited diseases when they shifted into an older age group. An increase of Japanese encephalitis vaccine coverage from 96% in 1995 to 100% in 2001 (9) appeared to confirm the above explanation. Nevertheless, areas where Japanese encephalitis vaccination had not been implemented also experienced a change in the age group with the most DHF. A final alternative explanation is the effect of herd immunity. Some researchers have observed that in places where dengue does not occur yearly, older age groups have higher rates of infection (10). However, dengue cases had been reported every year in Uttaradit, and the intervals between each epidemic were not long. We therefore, believed that the herd immunity hypothesis did not explain the observed changing age predominance in our study. The mean age of DHF case-patients in Uttaradit, Thailand, increased by >3 years between 1992 and 2001. This phenomenon may be important from a public health standpoint, as community and health-related personnel may still perceive DHF as a disease of only small children and unintentionally leave older children less protected or ignored. Further study is needed to confirm that the age group shifting of DHF predominance can be explained by the changes in locations where disease transmission takes place and possibly by effective household mosquito- elimination programs.

Statin therapy in patients with acute coronary syndrome: Low-density lipoprotein cholesterol goal attainment and effect of statin potency

Background Elevated low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk of coronary artery disease. Current guidelines recommend an LDL-C target of <70 mg/dL (<1.8 mmol/L) for acute coronary syndrome (ACS) patients, and the first-line treatment to lower lipids is statin therapy. Despite current guidelines and the efficacious lipid-lowering agents available, about half of patients at very high risk, including ACS patients, fail to achieve their LDL-C goal. This study assessed LDL-C goal attainment according to use of high and low potency statins in routine practice in Thailand. Methods A retrospective cohort study was performed by retrieving data from medical records and the electronic hospital database for a tertiary care hospital in Thailand between 2009 and 2011. Included were ACS patients treated with statins at baseline and with follow-up of LDL-C levels. Patients were divided into high or low potency statin users, and the proportion reaching the LDL-C goal of <70 mg/dL was determined. A Cox proportional hazard model was applied to determine the relationship between statin potency and LDL-C goal attainment. Propensity score adjustment was used to control for confounding by indication. Results Of 396 ACS patients (60% males, mean age 64.3±11.6 years), 229 (58%) were treated with high potency statins and 167 (42%) with low potency statins. A quarter reached their target LDL-C goal (25% for patients on high potency statins and 23% on low potency statins). High potency statins were not associated with increased LDL-C goal attainment (adjusted hazards ratio 1.22, 95% confidence interval 0.79–1.88; P=0.363). Conclusion There was no significant effect of high potency statins on LDL-C goal attainment. Moreover, this study showed low LDL-C goal attainment for patients on either low or high potency statins. The reasons for the low LDL-C goal attainment rate warrants further investigation.