The increased analgesic efficacy of cold therapy after an unsuccessful analgesic experience is associated with inferior parietal lobule activation.

Prior experiences of successful and failed treatments are known to influence the efficacy of a newly applied treatment. However, whether that carry-over effect applies to non-pharmacological treatments is unknown. This study investigated how a failed treatment history with placebo analgesic cream affected the therapeutic outcomes of cold-pack treatment. The neural correlates underlying those effects were also explored using functional magnetic resonance imaging. The effect of the placebo analgesic cream was induced using placebo conditioning with small (44.5 °C to 43.7 °C, negative experience) and large (44.5 °C to 40.0 °C, positive experience) thermal stimuli changes. After the placebo conditioning, brain responses and self-reported evaluations of the effect of subsequent treatment with a cold-pack were contrasted between the two groups. The negative experience group reported less pain and lower anxiety scores in the cold-pack condition than the positive experience group and exhibited significantly greater activation in the right inferior parietal lobule (IPL), which is known to be involved in pain relief. These findings suggest that an unsatisfying experience with an initial pain-relief treatment could increase the expectations for the complementary treatment outcome and improve the analgesic effect of the subsequent treatment. The IPL could be associated with this expectation-induced pain relief process.

Cardiovascular risk of nonsteroidal anti-inflammatory drugs in dialysis patients: a nationwide population-based study.

BACKGROUND: Given the cardiovascular risk of nonsteroidal anti-inflammatory drugs (NSAIDs), it is essential to identify the relationship between NSAIDs and cardiovascular outcomes in dialysis patients who have elevated cardiovascular risk. METHODS: A case-crossover study was conducted to assess the association of NSAIDs with major adverse cardiac and cerebrovascular events (MACCEs) and mortality using the Korean Health Insurance dataset. The case period was defined as 1-30 days prior to the event date and the control periods were defined as 61-90 days and 91-120 days prior to the event date. RESULTS: There were 3433 and 8524 incident dialysis patients who experienced MACCEs and mortality, respectively, after exposure to NSAIDs within 120 days before each event. NSAIDs significantly increased the risk of MACCEs {adjusted odds ratio [aOR] 1.37 [95% confidence interval (CI) 1.26-1.50]} and mortality [aOR 1.29 (95% CI 1.22-1.36)]. Nonselective NSAIDs, but not selective cyclooxygenase-2 inhibitors, significantly increased the risk of MACCEs and mortality. However, the MACCE and mortality risk did not increase in a dose-dependent manner in the analysis according to the cumulative defined daily dosage of NSAIDs. The incidence of MACCEs in the case period tended to be more common in patients who had recent exposure to NSAIDs than in patients who did not have recent exposure to NSAIDs. CONCLUSIONS: Clinicians should be particularly cautious when prescribing NSAIDs to dialysis patients considering the associations of NSAIDs with cardiovascular outcomes and mortality, which might occur independent of the dose and duration of exposure.

Quantitative CT-based structural alterations of segmental airways in cement dust-exposed subjects.

BACKGROUND: Dust exposure has been reported as a risk factor of pulmonary disease, leading to alterations of segmental airways and parenchymal lungs. This study aims to investigate alterations of quantitative computed tomography (QCT)-based airway structural and functional metrics due to cement-dust exposure. METHODS: To reduce confounding factors, subjects with normal spirometry without fibrosis, asthma and pneumonia histories were only selected, and a propensity score matching was applied to match age, sex, height, smoking status, and pack-years. Thus, from a larger data set (N = 609), only 41 cement dust-exposed subjects were compared with 164 non-cement dust-exposed subjects. QCT imaging metrics of airway hydraulic diameter (Dh), wall thickness (WT), and bifurcation angle (θ) were extracted at total lung capacity (TLC) and functional residual capacity (FRC), along with their deformation ratios between TLC and FRC. RESULTS: In TLC scan, dust-exposed subjects showed a decrease of Dh (airway narrowing) especially at lower-lobes (p < 0.05), an increase of WT (wall thickening) at all segmental airways (p < 0.05), and an alteration of θ at most of the central airways (p < 0.001) compared with non-dust-exposed subjects. Furthermore, dust-exposed subjects had smaller deformation ratios of WT at the segmental airways (p < 0.05) and θ at the right main bronchi and left main bronchi (p < 0.01), indicating airway stiffness. CONCLUSIONS: Dust-exposed subjects with normal spirometry demonstrated airway narrowing at lower-lobes, wall thickening at all segmental airways, a different bifurcation angle at central airways, and a loss of airway wall elasticity at lower-lobes. The airway structural alterations may indicate different airway pathophysiology due to cement dusts.

Epidemiology of pharmaceutically treated depression and treatment resistant depression in South Korea.

BACKGROUND: The epidemiology of pharmaceutically treated depression (PTD) and treatment resistant depression (TRD) is largely unknown in South Korea. The aim of this study was to develop a greater understanding of the characteristics of PTD and TRD in nearly the entire adult population in South Korea using the Health Insurance Review and Assessment Service (HIRA). METHOD: Diagnostic codes and prescription data for South Korean adults were extracted from the HIRA. Subjects were included in the PTD cohort if they received at least one prescription for antidepressants and were diagnosed with depression. TRD was defined as PTD having two or more regimen failures of antidepressants or antipsychotics. RESULTS: In 2012, there were 41,256,396 adults in South Korea with 834,694 meeting the criteria for PTD (2.0%). Among subjects with PTD, 57% stopped treatment in less than 28 days of antidepressant supply. Tricyclic and tetracyclic antidepressants were the most frequently used antidepressants as a first-line regimen for PTD (44.3% of PTD) followed by selective serotonin reuptake inhibitors (32.1% of PTD). Results also indicated that 34,812 subjects developed TRD (4.2% of PTD). Median PTD and TRD durations were 28 and 623 days respectively. Proportions of psychiatric and non-psychiatric comorbidities were higher in TRD cases than in PTD cases that were not treatment resistant. CONCLUSIONS: Despite a small proportion of patients with TRD, the prolonged duration of illness and higher comorbidity implies the need for better treatment.

Anesthetic Efficacy of Dexmedetomidine versus Midazolam When Combined with Remifentanil for Percutaneous Transluminal Angioplasty in Patients with Peripheral Artery Disease.

Anesthesia for percutaneous transluminal angioplasty (PTA) involves a high-risk population having a broad spectrum of pain character and intensity. This study delved the anesthetic efficacy of dexmedetomidine versus midazolam, when used with remifentanil. Seventy patients scheduled for femoropopliteal PTA were randomized into two groups receiving either intermittent midazolam boluses (0.03⁻0.05 mg/kg) (MR group) or dexmedetomidine 0.2⁻0.7 µg/kg/h after a loading dose of 1.0 µg/kg for 10 min (DR group), both with remifentanil. The primary endpoint was the patients' satisfaction (1⁻5, 5; extremely satisfied). Secondary endpoints included postprocedural pain scores (0⁻10, 10; worst imaginable pain) and adverse events. The satisfaction level of patients was significantly greater in the DR group compared with the MR group (4.0 [3.0, 5.0] versus 4.0 [2.0, 5.0] p = 0.021). The number of patients having a postprocedural pain score of at least 3 was significantly greater in the MR group compared with the DR group (10 [29%] versus 2 [6%], p = 0.013). The number of patients with hypotensive episodes was higher in the DR group (5 [14.7%] versus 0, p = 0.025), which could all be restored with ephedrine. The use of dexmedetomidine in conjunction with remifentanil may be a safe option that provides excellent patient satisfaction while potentially attenuating postprocedural pain.

Trends in prescription of pregnancy-contraindicated drugs in Korea, 2007-2011.

This study aims to evaluate changes in use of contraindicated drugs during pregnancy in Korea using the nationwide Health Insurance and Assessment Service (HIRA) database. Study drugs were 314 drugs that were announced as pregnancy-contraindicated on December 11, 2008. The study population consisted of the pregnant women who gave birth and were prescribed any of the drugs in 2007-2011 before giving birth. Pregnancy-contraindicated drug use was defined as the proportion of prescriptions among pregnant women that were for study drugs. The relative and absolute reductions in contraindicated drug use after the 2008 action were estimated with 95% confidence interval (CI) by medical institution type, region, and drug class. The predicted monthly contraindicated drug use was estimated by performing ordinary least-squares regression analysis of data before the action and compared with observed data after the action. Between 2007 and 2011, a total of 1,468,588 pregnant women received 1,796,208 prescriptions. Contraindicated drug use accounted for 15.96% of total prescriptions (N = 355,783) before the action but decreased to 11.52% (N = 453,832) afterward. Overall, the relative reduction was 27.77% (95% CI: 27.64%-27.90%) and greatest for hormones at 46.56% (95% CI: 46.21%-46.93%). The relative reduction was 55.43% (95% CI: 54.60%-55.43%) for all category X drugs, 17.09% (95% CI: 16.46%-17.75%) for category X drugs excluding hormones, and 0.14% (95% CI: 0.14%-0.15%) for category D drugs including hormones. A regulatory action toward pregnancy-contraindicated drugs led to moderate decrease in contraindicated drug use during pregnancy. Despite the decreases, contraindicated drugs were still widely prescribed to pregnant women, highlighting the need to develop strategies to assess and improve drug safety during pregnancy.

Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study.

OBJECTIVE: To define the risk of intracranial haemorrhage among patients treated with antidepressants and non-steroid anti-inflammatory drugs (NSAIDs), compared with the risk among those treated with antidepressants without NSAIDs. DESIGN: Retrospective nationwide propensity score matched cohort study. SETTING: Korean nationwide health insurance database between 1 January 2009 and 31 December 2013. PARTICIPANTS: Patients who began receiving antidepressants for the first time (index date) without a history of having received a prescription for antidepressants during the preceding year. Patients who had been diagnosed as having cerebrovascular diseases within a year before the index date were excluded. MAIN OUTCOME MEASURE: Time to first hospital admission with intracranial haemorrhage within 30 days after drug use. Matched Cox regression models were used to compare the risk of intracranial haemorrhage among patients who were treated with antidepressants with and without NSAIDs, after propensity score matching with a 1:1 ratio. RESULTS: After propensity score estimation and matching in a 1:1 ratio, the cohort used in the analysis included 4,145,226 people. The 30 day risk of intracranial haemorrhage during the entire study period was higher for combined use of antidepressants and NSAIDs than for use of antidepressants without NSAIDs (hazard ratio 1.6, 95% confidence interval 1.32 to 1.85). No statistically meaningful differences were found in risk of intracranial haemorrhage between the antidepressant drug classes. CONCLUSIONS: Combined use of antidepressants and NSAIDs was associated with an increased risk of intracranial haemorrhage within 30 days of initial combination.

Prevalence of antibiotic use for pediatric acute upper respiratory tract infections in Korea.

This study was conducted to estimate the prevalence of antimicrobial prescribing for acute upper respiratory tract infections (URI) among pediatric outpatients and to identify the national patterns of its use from 2009 to 2011 in Korea. Using National Patients Sample database from 2009 to 2011, we estimated the frequency of antibiotics prescribing for URI in pediatric outpatients with diagnoses of acute nasopharyngitis (common cold), acute sinusitis, acute pharyngitis, acute tonsillitis, acute laryngitis/tracheitis, acute obstructive laryngitis/epiglottitis, and acute upper respiratory infections of multiple and unspecified sites. The proportions of each antibiotic class were calculated by year and absolute and relative differences were estimated. Also, we investigated daily amount of prescribed antibiotics per defined population according to the type of medical care institution, physician specialty, and geographic region. The overall antibiotic prescribing proportion was 58.7% and its annual proportion slightly decreased (55.4% in 2011 vs. 60.5% in 2009; adjusted odds ratio, 0.82; 95% confidence interval, 0.82-0.83). Variations by the type of medical care institution were observed. Tertiary hospitals (45.0%) were less likely to prescribe antibiotics than primary care clinics (59.4%), hospitals (59.0%), and general hospitals (61.2%); they showed different tendencies in choosing antibiotics. Variations by physician specialty and region were also observed. Prevalence of antimicrobial prescribing for pediatric URI is still considered higher than that of western countries and varies by the type of medical care institution, physician specialty, and geographic region.

Differences in cytokines between non-suicidal patients and suicidal patients in major depression.

Several studies have shown that there is an imbalance between pro-inflammatory and anti-inflammatory cytokines in major depressive disorder (MDD). However, little is known about the role of cytokines in suicide. In the present study, amounts of IL-6, IL-2, IFN-gamma, IL-4, and TGF-beta1 produced by mitogen-stimulated whole blood were measured in 36 MDD patients who had recently attempted suicide, 33 non-suicidal MDD patients, and 40 normal controls. The severity of depression symptoms and suicidal behaviors was evaluated using Hamilton's depression rating scale (HDRS), the Lethality Suicide Attempt Rating Scale (LSARS), and the Risk-Rescue Rating (RRR). Non-suicidal MDD patients had significantly higher IL-6 production than suicidal MDD patients and normal controls (p<0.001). Suicidal MDD patients had significantly lower IL-2 compared with non-suicidal patients and normal controls (p<0.001). Both MDD groups, with or without attempted suicide, had significantly lower IFN-gamma and IL-4 and higher TGF-beta1 production. HDRS scores had significant positive correlations with IL-6, IFN-gamma, and the Th1/Th2 ratio and significant negative correlations with IL-4 in non-suicidal depression patients (p<0.005); however, these correlations did not hold true for suicidal patients. Suicidal MDD patients had no significant correlations between the LSARS or RRR scores and cytokine release. Our findings suggest that the immune response has distinct differences between non-suicidal patients and suicidal patients. Non-suicidal MDD may be associated with increased IL-6 production and a Th1/Th2 imbalance with a shift to Th1, while suicidal MDD may be associated with decreased IL-2.

Cytokine imbalance in the pathophysiology of major depressive disorder.

OBJECTIVE: A substantial body of evidence indicates that dysregulation of the immune system is associated with Major Depressive Disorder (MDD). Because most cytokines have pleiotropic effects, we measured various subsets of cytokines to examine the association between immune response and MDD. METHODS: Forty-eight hospitalized MDD patients and 63 normal controls were recruited. We measured in vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4 ratios for both groups. Depressive symptoms were assessed by Hamilton Depression Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant treatment. RESULTS: At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN-gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4 were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1 production were significantly lower than before treatment. CONCLUSION: We suggest that activation of monocytic proinflammatory cytokines, and inhibition of both Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD. TGF-beta1 may be associated with the regulation of monocytic cytokines as well as Th1 and Th2 cytokines in MDD.

Low plasma BDNF is associated with suicidal behavior in major depression.

Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain, has a known association with the pathophysiology of anxiety and depression. However, the role of BDNF in suicide has not been well investigated to date. This study examined plasma BDNF levels in 32 major depressive disorder (MDD) patients who had recently attempted suicide, 32 non-suicidal MDD patients, and 30 normal controls. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS). Plasma BDNF levels were measured by enzyme linked immunosorbent assay. BDNF levels were significantly lower in suicidal MDD patients (430.5+/-397.0 pg/ml) than non-suicidal MDD patients (875.80+/-663.02 pg/ml) or normal controls (889.4+/-611.3 pg/ml) (F=6.682, p=0.002). The most suitable cut-off point of BDNF level between suicidal depression and non-suicidal depression groups was 444.58 pg/ml. At this cut-off point, the sensitivity=68.7%, specificity=78.1%, positive predictive value=75.9%, and negative predictive value=71.4%. However, there was no significant difference in BDNF levels between the depressive control and normal control groups (p=0.996). LSARS and RRR did not reveal any significant correlations with BDNF levels in suicidal patients. In addition, BDNF levels were not different between fatal and non-fatal suicide attempts. These results suggest that reduction of plasma BDNF level is related to suicidal behavior in major depression and that BDNF level may be a biological marker of suicidal depression.

Psychological side-effects of clomiphene citrate and human menopausal gonadotrophin.

OBJECTIVE: This study evaluated the psychological side-effects of clomiphene citrate (CC) and hMG in women undergoing fertility treatment. METHOD: This study was a cross-sectional, self-report survey of 454 women at various stages of treatment for infertility. At the time of study, 139 women had not taken fertility drugs and 315 women had taken one or more cycles of CC or hMG. All subjects were asked to complete the State-Trait Anxiety Inventory (STAI). Women taking CC or hMG were also asked to complete a self-administered questionnaire on the side-effects of their medications. RESULT(S): In the CC group (n = 162) and hMG group (n = 153), 77.8% (126 of 162) and 94.8% (145 of 153) reported at least one side-effect, respectively. Irritability, mood swings, feeling down, and bloating had high frequencies in both CC and hMG groups, with a higher mean number of side effects reported in the hMG group (4.4 +/- 3.7 for the CC group and 6.8 +/- 3.7 for the hMG group, p < 0.001). There was no significant difference among the CC, hMG and no medication groups for mean state and trait anxiety scores. However, there were significant differences among the three side-effect groups (those who reported 1 to 4, 5 to 7, and more than 7 side-effects) for the mean scores of state (df = 2, F = 8.7, p < 0.001) and trait (df = 2, F = 11.9, p < 0.001) anxiety in women taking fertility drugs. CONCLUSION(S): Women taking CC or hMG reported high frequencies of psychological side-effects, and should be advised of these before treatment.

Low serum cholesterol is correlated to suicidality in a Korean sample.

OBJECTIVE: The aim of this study was to examine further the association between low total serum cholesterol and suicidal behaviour. METHOD: We measured the serum cholesterol levels in 231 patients admitted to an emergency room following a suicide attempt, in 231 age-,sex- and diagnosis-matched non-suicidal psychiatric controls, and in 231 age- and sex-matched normal controls. The suicide attempt patients were divided into five grades according to the degree of injury. RESULTS: The mean total cholesterol level of the suicide attempt patients was significantly lower than that of the psychiatric and normal controls. When the suicide attempt patients and non-suicidal psychiatric controls were divided by diagnosis, this significant relationship held true for major depressive disorders and personality disorders, but not for schizophrenia and bipolar disorders. Cholesterol level and the severity of suicide attempt were inversely correlated. CONCLUSION: The results suggest that cholesterol level may serve as a marker for suicide risk. Possible explanations are discussed.