ML 190

MRI-detection rate and incidence of lumbar bleeding sources in 190 patients with non-aneurysmal SAH.[Pubmed:28369075]

PLoS One. 2017 Apr 3;12(4):e0174734.

BACKGROUND: Up to 15% of all spontaneous subarachnoid hemorrhages (SAH) have a non-aneurysmal SAH (NASAH). The evaluation of SAH patients with negative digital subtraction angiography (DSA) is sometimes a diagnostic challenge. Our goal in this study was to reassess the yield of standard MR-imaging of the complete spinal axis to rule out spinal bleeding sources in patients with NASAH. METHODS: We retrospectively analyzed the spinal MRI findings in 190 patients with spontaneous NASAH, containing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH, diagnosed by computer tomography (CT) and/or lumbar puncture (LP), and negative 2nd DSA. RESULTS: 190 NASAH patients were included in the study, divided into PM-SAH (n = 87; 46%) and NPM-SAH (n = 103; 54%). Overall, 23 (22%) patients had a CT negative SAH, diagnosed by positive LP. MR-imaging of the spinal axis detected two patients with lumbar ependymoma (n = 2; 1,05%). Both patients complained of radicular sciatic pain. The detection rate raised up to 25%, if only patients with radicular sciatic pain received an MRI. CONCLUSION: Routine radiological investigation of the complete spinal axis in NASAH patients is expensive and can not be recommended for standard procedure. However, patients with clinical signs of low-back/sciatic pain should be worked up for a spinal pathology.

Use of Moderate-Intensity Statins for Low-Density Lipoprotein Cholesterol Level above 190 mg/dL at Baseline in Koreans.[Pubmed:28165667]

Basic Clin Pharmacol Toxicol. 2017 Oct;121(4):272-278.

The ACC/AHA 2013 guideline recommends high-intensity statin therapy for a decrease in low-density lipoprotein cholesterol (LDL-C) level by >50% among patients with baseline values of >/=190 mg/dL (approximately 4.872 mmol/L); however, this value should be modified before applying it to Korean populations. We investigated the statin-specific LDL-C-lowering effects in Korean patients with baseline LDL-C value >/=4.872 mmol/L. Data of patients prescribed a statin for the first time from January 2009 to December 2013 were assessed. In patients with baseline LDL-C value >/=4.872 mmol/L, laboratory data for a maximum of 6 months from the date of first statin prescription were collected. Among 33,721 patients who were prescribed a statin for the first time, 655 patients had a baseline LDL-C value >/=4.872 mmol/L (1.9%). Of these, 179 patients were analysed. Patients receiving moderate-intensity statins were divided into two groups based on LDL-C reduction rate (p = 0.0002), defined as moderate-high-intensity (atorvastatin 20 mg, rosuvastatin 10 mg, simvastatin 20 mg) and moderate-low-intensity (atorvastatin 10 mg, pitavastatin 2 mg, pravastatin 40 mg) statin groups. LDL-C reduction rates did not significantly differ between the moderate-high- and high-intensity statin groups (p = 0.4895). We found that some moderate-intensity statins demonstrated a LDL-C-lowering effect of more than 50% in Korean patients with a baseline LDL-C value >/=4.872 mmol/L. Our results reflect the need of a large-scale, randomized, controlled trial on partial reclassification of statins for patients with baseline LDL-C value >/=4.872 mmol/L before adopting ACC/AHC guidelines in Korea.

Depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from 190 593 people across 43 low- and middle-income countries.[Pubmed:28374652]

Psychol Med. 2017 Sep;47(12):2107-2117.

BACKGROUND: Despite the known heightened risk and burden of various somatic diseases in people with depression, very little is known about physical health multimorbidity (i.e. two or more physical health co-morbidities) in individuals with depression. This study explored physical health multimorbidity in people with clinical depression, subsyndromal depression and brief depressive episode across 43 low- and middle-income countries (LMICs). METHOD: Cross-sectional, community-based data on 190 593 individuals from 43 LMICs recruited via the World Health Survey were analysed. Multivariable logistic regression analysis was done to assess the association between depression and physical multimorbidity. RESULTS: Overall, two, three and four or more physical health conditions were present in 7.4, 2.4 and 0.9% of non-depressive individuals compared with 17.7, 9.1 and 4.9% among people with any depressive episode, respectively. Compared with those with no depression, subsyndromal depression, brief depressive episode and depressive episode were significantly associated with 2.62, 2.14 and 3.44 times higher odds for multimorbidity, respectively. A significant positive association between multimorbidity and any depression was observed across 42 of the 43 countries, with particularly high odds ratios (ORs) in China (OR 8.84), Laos (OR 5.08), Ethiopia (OR 4.99), the Philippines (OR 4.81) and Malaysia (OR 4.58). The pooled OR for multimorbidity and depression estimated by meta-analysis across 43 countries was 3.26 (95% confident interval 2.98-3.57). CONCLUSIONS: Our large multinational study demonstrates that physical health multimorbidity is increased across the depression spectrum. Public health interventions are required to address this global health problem.

Burden of disease attributed to ambient PM2.5 and PM10 exposure in 190 cities in China.[Pubmed:28321701]

Environ Sci Pollut Res Int. 2017 Apr;24(12):11559-11572.

Particulate air pollution is becoming a serious public health concern in urban cities of China. Association of disability-adjusted life years (DALYs) and economic loss with air pollution-related health effects demand quantitative analysis for correctional measures in air quality. This study applies an epidemiology-based exposure-response function to obtain the quantitative estimate of health impact of particulate matter PM2.5 and PM10 across 190 cities of China during years 2014-2015. The annual average concentration of PM2.5 and PM10 is 57 +/- 18 mug/m(3) (ranging from 18 to 119 mug/m(3)) and 97.7 +/- 34.2 mug/m(3) (ranging from 33.5 to 252.8 mug/m(3)), respectively. Based on the present study, the total estimated annual premature mortality due to PM2.5 is 722,370 [95% confidence interval (CI) = 322,716-987,519], 79% of which accounts for adult cerebrovascular disease (stroke) and ischemic heart disease (IHD). The premature mortality in megacities is very high, such as Chongqing (25,162/year), Beijing (19,702/year), Shanghai (19,617/year), Tianjin (13,726/year), and Chengdu (12,356/year). PM10 pollution has caused 1,491,774 (95% CI = 972,770-1,960,303) premature deaths (age >30) in China. Further, 3,614,064 cases of chronic bronchitis (CB); 13,759,894 cases of asthma attack among all ages; 191,709 COPD-related hospital admission (HA) cases; 499,048 respiratory-related HA; 357,816 cerebrovascular HA; and 308,129 cardiovascular-related HA due to PM10 pollution have been estimated during 2014-2015. Chongqing, Beijing, Baoding, Tianjin, and Shijiazhuang are the top five contributors to pollution-related mortality, accounting for 3.10, 2.71, 2.49, 2.20, and 2.02%, respectively, of the total deaths caused by PM10 pollution. The total DALYs associated with PM2.5 and PM10 pollution in China is 7.2 and 20.66 million in 2014-2015, and mortality and chronic bronchitis shared about 93.3% of the total DALYs for PM10. During this period, the economic cost of health impact due to PM10 is approximately US$304,122 million, which accounts for about 2.94% of China's gross domestic product (GDP). Megacities are expected to contribute relatively more to the total costs. The present methodology could be used as a tool to help policy makers and pollution control board authorities, to further analyze costs and benefits of air pollution management programs in China.

Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.[Pubmed:22737280]

ACS Chem Neurosci. 2012 Mar 21;3(3):221-236.

Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (kappa) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or agonists of high binding affinity (K(i) < 3 nM). In contrast to many important KOR ligands, the compounds presented here are highly modular, readily synthesized and, in most cases, achiral. The four new chemotypes hold promise for further development into chemical tools for studying the KOR or as potential therapeutic lead candidates.