This paper describes the first case of infection with a recently described novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), in Shanghai, China. The case is originally from Chizhou City, Anhui province within an endemic area for SFTSV. We describe the etiology, epidemiological characteristics, clinical diagnosis and treatment of this fatal case. This case is unique because major cause of death was renal failure, whereas other reported cases have been due to hemorrhage. The investigation and response to this case provides meaningful insight for the early and rapid diagnosis, treatment, prevention and control of severe fever with thrombocytopenia syndrome virus in non-endemic regions in China and globally. Bunyaviridae family, severe fever with thrombocytopenia syndrome virus (SFTSV), was first identified in China in 2010 [A novel member of phlebovirus genus of the SFTS mainly occurs in the spring and summer, especially among middle-aged residents who live in mountainous regions . SFTSV iAccording to the Chinese SFTS diagnosis and treatment guidelines, the case definition for SFTS includes a temperature above 38°C associated with thrombocytopenia, and fever with one or more bleeding symptoms . The case is confirmed by virus isolation, the detection of SFTS bunyavirus RNA, by novel bunyavirus IgG antibody seroconversion, and/or by a convalescent titer more than four times higher than in the acute phase .In our analysis, we present the case in terms of infection, diagnosis and treatment and then discuss the epidemiology and virology.The case under consideration in this article is a 40 year-old female farmer who lived in the countryside near the hilly areas outside Chizhou city, in Anhui Province, China, which is one of the central endemic areas. The patient had given birth by caesarean section in 1999, and raised her 13 year old in her hometown, while her husband left for work in another city. She had no other basic conditions or infectious diseases; except for a history of shistosomiasis in 2008. There was no history of previous drug or food allergies or blood transfusions. She was admitted to a hospital in Shanghai (400 km/78 miles from Chizhou) in the middle of May 2012.The patient had a sudden onset of fever (reaching a peak in temperature of 40°C) accompanied by muscle pain on May 16th 2012. She was reviewed at the local hospital, admitted and commenced on intravenous antibiotics, but no clinical improvement was observed. On May 19th, she was transferred to the hospital in Chizhou where she was treated with aztreonam and ribavirin, but the high fever continued. A tick-borne disease was suspected. On May 21st, the patient was transferred to a hospital in Shanghai, reporting fever, chills, body aches, and diarrhea occurring five to six times a day. The patient was clinically suspected of having SFTSV infection, admitted to the ICU (Intensive Care Unit), was given cefotiam, levodvopropizine, and other supporting and symptomatic treatments, but did not improve. The patient became apathetic on May 22nd and she was given vancomycin and other input platelet therapy, but her condition further deteriorated.The following day she had a stiff neck, accompanied by enlarged lymph nodes in the neck, axillary and mediastinal regions, and abnormal brain waves on electroencephalogram. On May 25th, the patient was in critical condition with shortness of breath, hypotension to 88/50 mmHg, significant oliguria with acute renal failure, severe acidosis, an abnormal flow index of the liver and kidneys, although there was no skin bleeding or blood stasis. Thereafter, she was treated with prednisone, platelet and plasma transfusions, and hemodialysis, but died on the same day (May 25th) of died of multi-organ failure, including kidney and respiratory failure, disseminated intravascular coagulation and septic shock.Laboratory tests showed that the patient’s white cell count decreased through most of the course of her illness, but then increased on the day of her death Table . The plaOn May 25th the results of an arterial blood gas was consistent with severe metabolic acidosis with respiratory compensation, as follows:2: 14.0 mmHg; PO2: 110 mmHg; HCO3-: 5.10 mmol/L; CO2-CT: 5.5 mmol/L; BE-ecf: -23.4 mmol/L; SBC: 8.5; BE-b: -21.1 mmol/L; SO2: 97%.pH: 7.17; PCOThe patient had several environmental exposures that may have contributed to her acquisition of SFTSV. She was engaged in collecting cotton, rice and tea until two weeks before the onset, and also had a contact history with birds and rodents and other wild animals in the local area. She had no skin damage or history of tick bites. She had had no known exposure to a person with a similar illness in the countryside, and no similar cases were found in the local town where the patient lived. Nineteen people, including three family members and sixteen medical staff (eleven doctors and five nurses) came into contact with the patient during the course of her hospitalization. No secondary cases of SFTS were found in any of these contacts.On May 25th, blood samples collected on the day of death were sent to Shanghai Municipal Center for Disease Control and Prevention, and confirmed as SFTSV. Confirmation was by real-time reverse transcriptase quantitative PCR . L, S anThe homology of the M sequence in this patient was 97.9–99.4% to other SFTSV strains, but showed only 68.2–68.6% similarity to other phleboviruses. The phylogenetic tree indicated that all Chinese SFTSV M genes are clustered together, but are very distantly related to other phlebovirus groups, such as the Sandfly fever group, , and the Uukuniemi group , and remained low at 61× 109/L on the day of death despite platelet transfusions. The elevated WBC count on the day of death may reflect a systemic inflammatory response or possible secondary bacterial infection. Her hemoglobin (Hb) and red blood cell (RBC) counts remained stable throughout her illness, consistent with the absence of any hemorrhagic complications from her thrombocytopenia and coagulation disorder. Late in the disease SFTSV can invade the heart, liver, kidney, gastrointestinal tract, and other vital organs, as well as the bloodstream [The illness duration prior to death in our patient was ten days, but she was confirmed as a SFTSV infection only on the day of her death. The laboratory tests showed that her white blood cell (WBC) count decreased during the early stages, but increased on the day of her death; platelet counts decreased progressively during the early stages and were persistently low until the day of her death. The platelet count decreased to 27× 10odstream ; our casodstream ,18.Molecular analysis confirmed that this patient’s SFTSV had very high homology to previously described strains from other regions in China. Further analysis of viral sequence variation did not reveal any characteristic genetic changes in our patient’s fatal strain when compared to genomes of SFTSV isolated from mild cases. This suggests there are not viral genetic factors affecting variations in virulence and pathogenicity between the fatal and mild cases.SFTS was previously reported in seven provinces of China: Henan, Hubei, Shandong, Anhui, Jiangsu, Liaoning, and Zhejiang. A national surveillance system for SFTS was built in these regions and nearby non-epidemic areas. Here we report a case of death from SFTSV, in a patient who lived in the Anhui mountain areas (endemic for SFTSV), but was treated and diagnosed in Shanghai. This SFTSV case highlights the potential risk to the healthy population in non-endemic regions, because the patient went to a large city, Shanghai, for medical treatment, and person-to-person transmission has been described . It willWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.PCO2: Partial pressure of arterial carbon dioxygen; PO2: Partial pressure of arterial oxygen; HCO3-: Calculated bicarbonate concentration; CO2-CT: Total carbon dioxide Content; BE-ecf: Base excess extracellular fluid; SBC: Standard bicarbonate concentration; BE-b: Base excess of blood; SO2: Arterial oxygen saturation.The authors declare that they have no competing interests.HP carried out the epidemiology survey and analysis and drafted the manuscript. JH and SL collected clinical data and conducted statistical analysis of the data. HS, YZ and JW participated in determination of survey on contacts and collected samples. XZ XZ and JQ performed the lab analysis. CW was responsible for the sequence analysis. ZY conceived the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.


To evaluate the effectiveness of a new multifactorial intervention to improve health care for chronic ischemic heart disease patients in primary care. The strategy has two components: a) organizational for the patient/professional relationship and b) training for professionals.Experimental study. Randomized clinical trial. Follow-up period: one year. Study setting: primary care, multicenter . For the intervention group 15 health centers are selected from those participating in ESCARVAL study. Once the center agreed to participate patients are randomly selected from the total amount of patients with ischemic heart disease registered in the electronic health records. For the control group a random sample of patients with ischemic heart disease is selected from all 72 health centers electronic records.Intervention components: a) Organizational intervention on the patient/professional relationship. Centered on the Chronic Care Model, the Stanford Expert Patient Program and the Kaiser Permanente model: Teamwork, informed and active patient, decision making shared with the patient, recommendations based on clinical guidelines, single electronic medical history per patient that allows the use of indicators for risk monitoring and stratification. b) Formative strategy for professionals: 4 face-to-face training workshops (one every 3 months), monthly update clinical sessions, online tutorial by a cardiologist, availability through the intranet of the action protocol and related documents.Measurements: Blood pressure, blood glucose, HbA1c, lipid profile and smoking. Frequent health care visits. Number of hospitalizations related to vascular disease. Therapeutic compliance. Drug use.This study aims to evaluate the efficacy of a multifactorial intervention strategy involving patients with ischemic heart disease for the improvement of the degree of control of the cardiovascular risk factors and of the quality of life, number of visits, and number of hospitalizations.NCT01826929 The medical, health care, financial, personal and family burden of chronic disease is one of the main threats to the sustainability of the health system. At present, 70% of health care expenditure is used to treat chronic diseases . AccordiCardiovascular disease (CVD) is one of the main chronic diseases, and is in fact the leading cause of death in the Spanish population. In 2007 it accounted for 124,126 deaths in Spain, representing 32% of all deaths .Lifestyle changes  have been shown to decrease cardiovascular morbidity and mortality in patients with IHD. In addition, much evidence now exists concerning pharmacological treatment aimed at the associated risk factors .The latest European guidelines aim to increase the involvement of the primary care professionals in the implementation of the preventive activities for these patients. The guidelines emphasize a patient-centered approach, joint decision-making, and the importance of establishing realistic and feasible objectives, as tools to improve compliance with medication and lifestyle changes –8]. A r. A r8]. However, difficulties exist when incorporating the results of the various studies into clinical practice. Comparison of the results from the EUROASPIRE I to the EUROASPIRE III studies, in patients with IHD, shows that the prevalence of risk factors remains high: smoking hardly changed , obesity (body mass index ≤ 30) increased from 25% to 32.6% and 38%, and poorly controlled blood pressure (BP) (≥ 140/90 mmHg) changed very little . Only in the prevalence of hypercholesterolemia was an important decrease observed, from 94.5% to 76.7% and 46.2%. Concerning the use of drugs, between the EUROASPIRE I and the EUROASPIRE III studies  antiplatStudies carried out in our area show that 54% of the patients with a history of myocardial infarction had hypercholesterolemia, 41% had high blood pressure, 11% were smokers, and 19% were obese; in addition, there was a clear underuse of medication ” OR “Myocardial Ischaemia/epidemiology” [MeSH], OR “Coronary Artery Disease”[MeSH Terms] AND “Secondary prevention”. A second search included: “Patient Education” as Topic/methods OR “Patient Participation” OR “Self-Help Groups” OR “Program Evaluation” AND “Myocardial Ischaemia”.In the Cochrane database we used the MeSH terms: Patient Education, Lifestyle.The search was limited to publications in the last 5 years, only items with abstracts, studies in humans, and a publication type of Meta-Analysis and Systematic Review. In the Cochrane database we also used the search limit of the last 5 years.Table Figure This study protocol has been reviewed and approved by the Ethics Committee for Clinical Trials from San Juan de Alicante Hospital (Comite Ético de Investigación Clínica (CEIC) del Hospital Universitario de San Juan de Alicante), on December 2nd, 2009.The study is conducted according to the standards of the International Guidelines for Ethical Review of Epidemiological Studies  and the recommendations of the Spanish Society of Epidemiology about the review of ethical aspects of epidemiological research.All information relative to the patient’s identity is considered confidential. The data generated during the study will be handled according to the Law 5/1999 and corresponding normative. Any researcher with access to the data used in the study will be required to sign a document guaranteeing confidentiality.All patients must read the “Patient Information Form” and sign a document giving their consent.IHD is one of the main causes of death despite the great capacity for prevention that is available. Nowadays, multiple therapeutic tools of proven efficacy exist to control the main CVRF, as well as guidelines and protocols endorsed by the main scientific societies –7,19].,19.7,19]However, the degree of control of the CVRF in patients with IHD is low –17], wh, wh17], The CCM  considerAccordingly, the present study involved an organizational intervention based on CCM together with an educational intervention, integrating cardiology service professionals and primary care professionals , in an attempt to improve the degree of control of CVRF and decrease the number of hospitalizations.This intervention aims to increase the degree of self-control for these patients as well as their ability for self-care and decision making to improve their long-term survival. At the same time, the greater degree of information and education can facilitate the increase in compliance that should result in an improvement in the therapeutic objectives.The health care team-work methodology will be modified with more resolute and specific patient-centered office visits, without increasing the work load in the primary care offices. This is aimed at reducing clinical inertia.The Abucasis computer system, available in secondary and primary care offices, facilitates the interaction between levels of health care as well as being a common and unique site for the patient to record and control the main CVRF.The validity of the results, which depends on the representativeness of the sample, is controlled by the selection criteria designed and in relation to study power, through the sample size calculated taking into account any unexpected loss by controlling the random error.Some multifactorial interventions have been published specially based on nurse work  but no vIn conclusion, this study will provide information about the efficacy of a patient-centered intervention based on the CCM. Actions will be centered on identifying the higher-risk patients, such as those in secondary prevention; on greater patient information and capacity, favoring autonomy; on shared decision making to establish and reach the control objectives; and an individualized programming of appointments, relying for all this on the teamwork of primary care nurses and physicians under the supervision of the reference cardiology service.IHD: Ischemic heart disease; HC: Health centers; CVD: Cardiovascular disease; CVRF: Cardiovascular risk factors; CCM: Chronic care model; EPP: Expert patient program; LDL: Low density lipoprotein; HDL: High density lipoprotein; SVMFiC: Valencian medical society of family and community medicine. HbA1c: glycated hemoglobin.The authors declare they have no competing interests.Conception of the idea for the study: DO, ER, MG and AIN. Development of the protocol, organization and funding: DO, ER, MG and AIN. Study design assistance: AC, JN, CC, SP, ES, FB, JB, MAN, VB and VFG. Writing of the manuscript: ER, DO and AIN. All authors have critically read the final manuscript draft, to make contributions, and have approved the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/13/293/prepub


Background. To evaluate the effect of rosiglitazone, fenofibrate, or their combined use on plasma lipids in normoglycemic healthy adults. Methods and Results. Subjects were randomized in a double-blind fashion to rosiglitazone + placebo, fenofibrate + placebo, rosiglitazone + fenofibrate, or matching double placebo. The between-group difference in the change in fasting TG, high-density lipoprotein cholesterol (HDL-C), LDL-C, and plasma apolipoproteins A-I, A-II, and C-III level were compared after 12 weeks of treatment. A total of 548 subjects were screened and 41 met the inclusion criteria. After 12 weeks of therapy, the median change in the triglyceride levels showed a significant reduction ranging from 47 to 55 mg per deciliter in the fenofibrate only and rosiglitazone/fenofibrate groups compared with placebo (P = 0.0496). However, the rosiglitazone only group did not show significant change in triglyceride level. The change in the Apo AII showed increase in all the treatment groups compared with placebo (P = 0.009). There was also significant change in the Apo CIII that showed reduction of its level in the fenofibrate only and rosiglitazone/fenofibrate groups (P = 0.0003). Conclusion. Rosiglitazone does not appear to modulate hypertriglyceridemia in patients with elevated triglycerides independent of glucose metabolism. The thiazolidinediones (TZDs), which include troglitazone (withdrawn by the FDA), rosiglitazone, and pioglitazone, correct hyperglycemia in diabetic patients by increasing insulin sensitivity in both the liver , 2 and sClinical trials using TZDs in type 2 diabetic subjects have observed that these agents also favorably impact plasma lipid and apolipoprotein concentrations. Following eight weeks of treatment with rosiglitazone  in 243 type 2 diabetic patients, the mean HDL-C increased by 6% and TG by 2%. The increase in the LDL-C concentration (9%) was accompanied by a shift in small, dense LDL to large, buoyant LDL in 52% of the treated subjects. The shift in LDL size occurred independent of a significant triglyceride reduction, which is in contrast to several studies reporting that increases in LDL size are significantly correlated with a decrease in the plasma concentrations of total and very-low-density lipoproteins (VLDL) and triglycerides [Three distinct peroxisome proliferator-activated receptors (PPARs), termed alpha, beta, and gamma, modulate intracellular lipid and glucose metabolism through controlling gene expression when activated . ActivatThe Rosiglitazone and Fenofibrate Additive Effects on Lipids (RAFAEL) trial was designed to evaluate the effect of rosiglitazone when combined with fenofibrate on the plasma lipid and lipoprotein concentrations assuming direct influence on the synthesis of the apolipoproteins that are responsible for VLDL and HDL metabolism in normo-glycemic individuals with elevated TG as well as the mechanism of action of rosiglitazone.The Rosiglitazone and Fenofibrate Additive Effects on Lipids (RAFAEL) protocol was reviewed and approved by the institutional review board at Brooke Army Medical Center where the trial was conducted. The study was sponsored by GlaxoSmithKline , ClinicalTrials.gov ID: NCT00819910.All patients provided written informed consent to participate in the study. Patients were eligible if they were 18 years of age or older, had a fasting glucose <100 mg/dL, fasting LDL-C <160 mg/dL, and a triglyceride <400 mg/dL. Patients taking any cholesterol lowering medication prior to entering the study underwent a “wash-out” period of two weeks. Patients were excluded if they had a history of congestive heart failure, evidence of renal impairment (Cr > 1.4 mg/dL), history of liver disease , known diabetes mellitus or impaired fasting glucose (fasting glucose > 100 mg/dL), pregnant or breast feeding, prior history of an acute coronary syndrome, myocardial infarction, or coronary revascularization, life-threatening disease with an estimated survival of less than 3 years, or inability to take rosiglitazone and/or fenofibrate.At the beginning of the trial, candidates were instructed to fast for 12 to 15 hours for the initial visit. Baseline fasting lipid profile with direct LDL-C measurement, fasting glucose, hepatic function and plasma concentrations of apolipoproteins A-I, A-II, and C-III were drawn at the initial visit. Based on the concentration of total cholesterol, triglyceride, and glucose, eligible subjects were randomized within 7 days of providing the initial blood sample. Subjects, who met the inclusion criteria, were then randomized to one of 4 groups: rosiglitazone (dose 8 mg daily) plus placebo; fenofibrate (145 mg daily) plus placebo; fenofibrate (145 mg daily) plus rosiglitazone (dose 8 mg daily); or double placebo for a total of 12 weeks. At the mark of 12 weeks , the initial laboratory collections were repeated to assess the difference in concentration of fasting glucose, insulin, hepatic transaminases, fasting lipid profile, apolipoproteins, HDL size, LDL size, and statistical difference from baseline. At this visit, subjects were asked to return their bottles for a pill count to assess compliance and assessment of adverse events was done at this time. All blood samples were shipped to Oklahoma Research Foundation for apolipoproteins A-I, A-II, and C-III assessments and the remainder of the labs were shipped to Quest Diagnostic Labs.The primary end-point with respect to efficacy was the between-group difference in the change in TG levels after 12 weeks of treatment. Secondary end-points included the between-group difference in the change in HDL-C, LDL-C, Apo AI, Apo AII, and Apo CIII levels. The primary safety end-point was the incidence of elevations in AST and ALT, defined as more than three times the upper limit of normal.The null hypothesis was that there will be no difference in the serum triglyceride level between treatments. The alternative hypothesis is that there will be at least a 20% decrease in the serum triglyceride level in the fenofibrate, rosiglitazone, fenofibrate, and rosiglitazone treatment groups relative to the placebo group.P values < 0.05 were considered statistically significant.The sample size was determined to be 16 subjects in each arm  based on eight comparisons between groups before and after treatment with 80% power and a 95% level of confidence. Anticipating a 25% drop out rate, aimed for 20 subjects per group for a total of 80 subjects, but we were only able to recruit 41 subjects due restrictions to the prescriptive pattern with thiazolidinediones per the Food and Drug Administration that occurred after the start of the trial. Statistical differences among the four treatment groups were assessed by comparing the median changes among groups using Kruskal-Wallis one-way analysis of variance on ranks. Between October 2008 and August 2010, a total of 548 patients were screened at one center. Of the 548 patients who were screened, a total of 41 patients met the inclusion criteria and were randomly assigned one of the prespecified study groups. As of October 2010, follow-up assessment, with ascertainment of end points, was completed in 73% of the patients in the study. There were seven (17%) patients that did not complete the study due to either lost of followup or adverse events that make them to withdraw from the study. The baseline characteristics of the patients who were enrolled in the study are shown in P = 0.0496) (P = 0.0152) (P = 0.009) (P = 0.0003)  . However 0.0152) . There w 0.0152) . In rega= 0.009) . There w 0.0003) . There w 0.0003) .There were adverse events reported in seventeen patients in the study. Four adverse events led to discontinuation of therapy in most cases during the study (three ADE's in the combined arm and one in the double placebo arm). There was one patient in the combined (rosiglitazone and fenofibrate) group who was hospitalized during the study due to acute renal failure (SAE's). The most common adverse effects were headache and gastrointestinal complains such as abdominal discomfort, diarrhea, nausea, and vomiting. The level of transaminases did not increase significantly in any of the patients in each treatment group. Clinical trials have shown that the use of thiazolidinedione in type 2 diabetic patients has shown favorable impact in plasma lipid and lipoprotein concentrations in addition to glycemic control. The mechanism involved in the plasma lipid and lipoprotein concentration changes in type 2 diabetics by thiazolidinedione remains unclear. The RAFAEL trial is the first study performed in the literature to evaluate the effect of thiazolidinedione to plasma lipid and apolipoprotein concentration in normoglycemic population to assess mechanism of action. After 12 weeks of therapy, the median change in the triglyceride level was only significant in the group that received fenofibrate as expected due to its known mechanism of action. We also saw significant changes in the fenofibrate/rosiglitazone group which were most likely due to the fenofibrate alone since it was very similar change compared to the fenofibrate alone. In addition, the rosiglitazone group did not show a significant change in the triglyceride level. Therefore, combination therapy of rosiglitazone and fenofibrate did not show trend towards additive reduction in triglyceride levels.In regards to the apolipoproteins, all treatment groups showed significant increase in the median change of Apo AII compared to placebo. Also, median change of Apo CIII showed significant reduction of its level in the fenofibrate only and fenofibrate/rosiglitazone groups. However, this change was not seen in the rosiglitazone group only. As a result, rosiglitazone does not affect Apo CIII levels and subsequently lipoprotein lipase activity as anticipated. However, rosiglitazone increases Apo AII levels without observed change in HDL-C in patients with type 4 hyperlipidemia with normoglycemia. Fibrates impact on TG reduction is known to correlate with its reduction of Apo CIII in animal models . The absSeveral limitations of the current study should be considered. First, the study was terminated early per FDA recommendations restricting rosiglitazone use. Second, recruitment of patients was slow due to deployment restraints and the publication of various studies evaluating the cardiovascular complications of rosiglitazone. Therefore, the sample size was insufficient for power analysis, and strength of statistical significance was adversely affected in all end points.In conclusion, the results from our study suggest the favorable effects of rosiglitazone on plasma lipid and lipoprotein concentrations in diabetic patients noted in prior studies are not independent of glucose control as noted in our normoglycemic cohort of subjects.


Bivalve mitochondrial genomes exhibit a wide array of uncommon features, like extensive gene rearrangements, large sizes, and unusual ways of inheritance. Species pertaining to the order Solemyida (subclass Opponobranchia) show many peculiar evolutionary adaptations, f.i. extensive symbiosis with chemoautotrophic bacteria. Despite Opponobranchia are central in bivalve phylogeny, being considered the sister group of all Autobranchia, a complete mitochondrial genome has not been sequenced yet.Solemya velum: A-T content, gene arrangement and other features are more similar to putative ancestral mollusks than to other bivalves. Two supranumerary open reading frames are present in a large, otherwise unassigned, region, while the origin of replication could be located in a region upstream to the cox3 gene.In this paper, we characterized the complete mitochondrial genome of the Atlantic awning clam S. velum mitogenome retains most of the ancestral conchiferan features, which is unusual among bivalve mollusks, and we discuss main peculiarities of this first example of an organellar genome coming from the subclass Opponobranchia. Mitochondrial genomes of Solemya  and Haliotis (for gastropods) seem to retain the original condition of mollusks, as most probably exemplified by Katharina.We show that  In animals, the mitochondrial genome (mtDNA) is typically a small, circular and compact molecule, generally encoding for 37 genes: 13 protein-coding genes (PCGs), 2 rRNAs, and 22 tRNAs -10, mosti.e. length, gene arrangement, strand assignment, gene duplications and losses, nucleotide composition, and more. Within mollusks, gastropods and bivalves show extensive variations, even with differences within the same family or genus ), Meretrix lamarckii.As expected from the high plasticity of molluscan  mitochondrial genomes, many differences were found between r Figure . If tRNASolemya mtDNA contains all genes of the standard metazoan mitochondrial genome . Whether the absence of atp8 gene is real or just an outcome of incorrect annotations , itsatp6 and atp8 on the same strand [atp8 itself is also lacking in some of them; [atp6 and atp8 are neighboring in S. velum (Tab 3). The same association can be found in basal mollusks, like C. nitidulum and K. tunicata, and in other conchiferans, like cephalopods , Caenogastropoda, and Heterobranchia .Moreover, it is common in metazoans to find neighboring e strand  and it he strand ,95. Tougof them; ), nevertG. eborea): S. velum has a high A-T content (68.11%), being significantly more similar to aculiferans and cephalopods than to other bivalves . Irrespective of the functional constraints and gene features, we found an unbiased, when not low, G-T content in the “ + ” strand  and 74.12%  and 69.Solemya velum, genes are evenly distributed among “ + ” and “-” strands, with 18 and 19 genes, respectively. Even if a H-biased distribution of genes is found in other lophotrochozoans, like annelids, brachiopods, bryozoans and platyhelminths  strand in S. velum? Patterns evidenced in S. velum resemble those of N. macromphalus[Katharina[All genes are located on the same strand in Amarsipobranchia, and most of them in Palaeoheterodonta. Contrastingly, in e, f.i., ,27), an e, f.i., ) and, noromphalus. Contrarromphalus and in KKatharina. It seemS. velum control region are the unassigned regions UR7 and UR8  should contain or neighbor the origins of replication (ORs).  and, specox3 was used as the starting point  is the heavy (antisense) strand, while the strand we call “-” is the light (sense) strand; (ii) the CR of S. velum mtDNA is located immediately before cox3 in the UR7 region; (iii) as UR7 is located at the H/L switch, we suggest this to be the OR of both strands, working in either direction. suggestet Figure , being ttrnM, trnC, trnY, trnW, trnQ, and trnE, a situation already signaled in the family Vermetidae [Inversidens japanensis[Mytilus spp. is located after a group of 7 tRNAs and the rrnL gene [Mimachamys nobilis is located after a cassette of 8 tRNAs [Meretrix spp. is located after 7 consecutive tRNAs [The region of the putative OR of the H strand encompasses UR7 and a cassette of tRNAs on the “-” strand, namely rmetidae  and in tapanensis. As showapanensis, tRNAs ornL gene ; the maj 8 tRNAs ; the CR ve tRNAs ,110,111.Solemya mtDNA, the function of UR8 remains unknown. Its length and secondary structure may have some kind of signaling function, but it is quite noteworthy that two ORFs were found here: ORF117 and ORF195. Are they functional or not? Remarkably, they span over the almost complete UR8, leaving only small unassigned nucleotide stretches of 37, 11, and 12 bp, similar to other intergenic spacers in S. velum mtDNA . Although it is nested in the A-T rich UR8 (70.43%), it has a lower A-T content (59.83%), so that its composition is actually different from the rest of the UR8. Moreover, notwithstanding the low (for S. velum) A-T content, the most used codon is UUU (Phe), which is also among the most used ones in all PCGs of this mtDNA, and therefore its codon composition is similar to that of other PCGs. The nucleotide pattern at four-fold degenerate sites is also consistent with other PCGs ; consistently, the most used codon is AAA (Lys). However, possible homology of ORF195 with membrane proteins is confirmed to some extent by the finding of a large transmembrane domain; the presence of a signal peptide constitutes a further It is not easy to assign to a protein a functional role only relying on bioinformatics data: expectedly, given the low homology scores and the short length of both ORFs, many different kinds of proteins and ligands were suggested by tools hosted on the @TOME 2.0 server. The presence of supranumerary ORFs in mitochondrial genomes has been reported elsewhere  out of 32 in the C-terminal half of the protein. Interestingly, this architecture is the same described by  for suprS. velum mtDNA might constitute an evidence of the ancestral presence of such supranumerary ORFs in all bivalves. However, it has to be noted that this remains an in silico analysis and that some features of ORF195 could be randomly due to the high A-T content : therefore, detailed analyses of mRNA gene expression are required to shed light on these issues.The presence of a putative transmembrane signaling peptide in ORF195 and the DNA-binding signal in ORF117 may suggest a regulatory role for both these proteins; moreover, their presence in the Solemya is unexpected, being nested within Gastropoda in our tree. However, node support is evidently very low (44.5), so our analysis does not point to a diphyly of Bivalvia, but rather to a polytomy at the base of the tree, including Solemya, Katharina and Haliotis. We may suggest that the lineage leading to Opponobranchia arose so early in the molluscan radiation that little or no phylogenetic signal of this event may be retrievable in Solemya mtDNA. The structural similarities of Solemya mtDNA to Haliotis and Katharina, and the huge differences to other bivalvian mitochondrial genomes, may have affected the clustering, hence the incorrect weak relationship to Gastropoda, which has rather to be considered an artifact.The position of The diphyly of Bivalvia is not a new find however , evSolemya gene order connects to the Katarina one by a single gene inversion event  to this archaic condition that the gene order of S. velum is useless in tracing phylogenetic relationships between Opponobranchia and other bivalves. Only the invention of a slow-evolving autobranch bivalve mtDNA (if it exists) would help to trace Bivalvia deep phylogenetic relationships based on mtDNA gene arrangements.Mitochondrial gene arrangement may better help in tracing basal phylogenetic relationships -26. Remat Figure , once aga  sources point towards the same conclusion: S. velum retains most of the ancestral mtDNA features of conchiferans, like H. rubra does within gastropods. The large similarities found with K. tunicata, an outgroup of conchiferans, on one side, and the great differences found with other known bivalves, on the other side, lead us to polarize genomic characters and conclude that the mtDNA of S. velum has been probably “freezed” in a condition very similar to that of the most recent common ancestor of Opponobranchia and Autobranchia.In previous paragraphs we extensively discussed many features of the mitochondrial genome of S. velum and Autobranchia is intriguing: in facts, no mtDNA representing an intermediate state is known to date, the only exceptions being some genomic features of Palaeoheterodonta . In the branch leading to Autobranchia, mitochondrial genome evolved on its own, like for the translocation of most – if not all – genes on a single strand; the decrease in A-T content; a possible tendency towards heavy changes in atp8 gene; multiple and lineage-specific events of gene rearrangement. The evolution of Autobranchia seems to be tightly coupled with a dramatic increase of gene rearrangement events. Which factors triggered this boost of genomic evolution, while the main cladogenetic event leading to the Opponobranchia-Autobranchia split was taking place in the lower Cambrian [Ledella ultima[If this is true, the wide discontinuity between Cambrian ? An exhaCambrian ,17: furtla ultima is very The authors declare that they have no competing interests.FP participated in the design of the study and in molecular lab work, analyzed the data and drafted the manuscript; AR carried out the molecular lab work and analyzed the data; MP conceived the study and helped to draft the manuscript. All authors read and approved the final manuscript.Primers used in this study for Long-PCR reactions. Primers that were used for the same experiment as a forward/reverse couple were marked with the same letter. The position of the primer annealing site on the complete molecule is reported in the “Target” column [” column -121.Click here for filePrimers used in this study for routine PCR reactions. Primers that were used for the same experiment as a forward/reverse couple were marked with the same letter. The position of the primer annealing site on the complete molecule is reported in the “Target” column [” column -123.Click here for fileThe dataset used for this study.Click here for fileSecondary structures of tRNAs.Click here for fileNucleotide composition of Solemya velum mitochondrial genome.Click here for fileMitogenomic features of taxa used in this study. %UNs, percentage of unassigned nucleotides over the total length of the genome; H, number of genes on the putative H strand; L, number of genes on the putative L strand; aa, number of amminoacids encoded by the totality of protein coding genes (excluding stop codons). The rrnS gene is duplicated in C. gigas; length of either copy is reported.Click here for fileSecondary structures of regions between two consecutive PCGs.Click here for fileCodon usage in Solemya velum mitochondrial genome. The total frequency of each amminoacid is reported under the three-letter/one-letter name; underlined codons correspond to anticodons of mitochondrial tRNAs. All truncated (TA-/T--) stop codons were attributed to TAA. RSCU, Relative Synonymous Codon Usage.Click here for fileUnassigned regions longer than 10 bp.Click here for filePhylogenetic Representativeness. Test is reported as in [a) the original master list of mollusks taken from [b) a set of 100 shuffled master lists simulating taxonomical revisions. In both cases, AvTD is plotted on the left axis in the upper part of the chart and VarTD on the right one in the lower part. Sample size is plotted on x-axis; the greatest AvTD value (upper thick continue line), the AvTD mean (thin continue line), the AvTD 95% lower confidence limit (lower thick continue line), the VarTD 95% upper confidence limit (upper thick dashed line), the VarTD mean (thin dashed line), and the lowest VarTD value (lower thick dashed line) are shown. All these lines (with the exception of greatest AvTD and lowest VarTD) are shown as two-tailed 95% confidence limits for shuffling test (b). Sample used for this work is shown as a black diamond (AvTD)/circle (VarTD). ed as in  for (a) ken from  and (b) Click here for fileAmminoacid substitution models selected by ProtTest 3.2  and pipeClick here for file


Primary focal hyperhidrosis is a health problem, which has negative effects on the patient's quality of life and significantly affects the patients’ daily activities, social and business life. The aim of this study is to evaluate temperament and character properties of patients diagnosed with primary focal hyperhidrosis.Fifty-six primary focal hyperhidrosis (22.42 ± 7.80) and 49 control subjects (24.48 ± 5.17) participated in the study. Patients who met the diagnostic criteria for PFH were referred to psychiatry clinic where the subjects were evaluated through Structured Clinical Interview for DSM Disorders-I and Temperament and Character Inventory.In order to examine the difference between the PFH and control group in terms of temperament and character properties, one-way Multivariate Analysis of Variance (MANOVA) was conducted. In terms of temperament properties, PFH group took significantly higher scores than control group in Fatigability and asthenia dimension. In terms of character properties, PFH group scored significantly lower than control group in Purposefulness , Resourcefulness , Self-Directedness and scored significantly higher than control group in Self-forgetfulness and Self-Transcendence.Temperament and character features of PFH patients were different from healthy group and it was considered that these features were affected by many factors including genetic, biological, environmental, socio-cultural elements. During the follow-up of PFH cases, psychiatric evaluation is important and interventions, especially psychotherapeutic interventions can increase the chances of success of the dermatological treatments and can have a positive impact on the quality of life and social cohesion of chronic cases. Primary focal hyperhidrosis (PFH) is a disorder of excessive, bilateral and relatively symmetric sweating typically localized to specific body areas such as axillae, palms and soles. For the diagnosis of PFH only excessive sweating in those regions is not enough. Sweating must be visible, continuing for at least six months without an underlying disease and have at least two other diagnostic criteria for PFH -3. It isCloninger's psychobiological model of personality has recently been widely used to examine the cases with dermatologic diseases. In this model, personality is composed of four temperament and three character dimensions. Genetic structure affects these temperament dimensions by the rate of 40-60% and character dimensions by the rate of 10-15%, while environmental factors affect temperament and character dimensions by the rate of 30-35% ,8. In adOnly one study was found which has investigated the temperament and character properties of PFH patients. The results of the study revealed that the total novelty seeking score in hyperhidrosis was significantly lower than in controls. The total reward dependence and persistence scores were significantly higher in hyperhidrosis patients. Regarding character dimensions, the total score in each of the subscales self-directedness, cooperativeness and self-transcendence was found to be higher in hyperhidrosis patients .Our aim in this study is to evaluate temperament and character properties of patients diagnosed with primary focal hyperhidrosis, and to compare the findings with a healthy control group.Seventy-one patients, who applied to the dermatology clinic of Gulhane School of Medicine, Ankara, Turkey, with complaints of focal excessive sweating in their hands, feet or axilla, were evaluated by a dermatologist. In order to eliminate the possible secondary causes such as hyperthyroidism, hiperpitutiarizm, diabetes mellitus, the analysis including of blood count, routine, fasting blood glucose, thyroid hormones, cortisol and PTH were conducted. Patients who met the diagnostic criteria for PFH were referred to psychiatry clinic where the subjects were evaluated through Structured Clinical Interview for DSM Disorders-I (SCID-I) and Temperament and Character Inventory (TCI). Control group consisted of healthy voluntary individuals who had no psychiatric or physical disease. Control group is formed by the individuals accompanying the patients in the hospital from different clinics. Control group also evaluated via SCID-I and TCI.Fifteen out of 71 patients were excluded from the study due to diabetes mellitus (n=2), hyperthyroidism (n=1), hyperpituitarism (n=1), and psychiatric disorders . Fifty six primary focal hyperhidrosis and 49 control subjects ranging from 17 to 61 years old participated in the study. In terms of age, PFH group (22.42 ± 7.80) was not significantly different from control group (24.48 ± 5.17), t(103)=−1.15, n.s. Socio-demographic characteristics of the sample were presented in Table Temperament and Character Inventory (TCI): Temperament and Character Inventory [nventory  is a selnventory  and Arkanventory  conducteStatistical analysis was performed using SPSS for Windows 16.0. . One-way Multivariate Analysis of Variance (MANOVA) was conducted to examine the differences between the PFH and control groups in terms of temperament and character properties.2=.36]. Univariate analyses were examined to find out group differences on temperament and character dimensions with Bonferroni adjustment. Alpha levels lower than 0.0016 were accepted as significant. In terms of temperament properties, PFH group took significantly higher scores than control group in Fatigability and asthenia (HA4). In terms of character properties, PFH group scored significantly lower than control group in Purposefulness (SD2), Resourcefulness (SD3), Self-Directedness (SD), and scored significantly higher than control group in Self-forgetfulness (ST1) and Self-Transcendence (ST) dimensions. Results of the MANOVA were presented in Table In order to examine the difference between the PFH and control group in terms of temperament and character properties, one-way Multivariate Analysis of Variance (MANOVA) was conducted. Results revealed that group (PFH and control) had a main effect on temperament and character properties [Multivariate F25,67)=1.55, p < .05; Wilks’ Lambda=.63; partial η5,67=1.55Limited number of research related to psychopathology in hyperhidrosis gave conflicting results. Although some studies found that patients with hyperhidrosis have no psychopathology and symptoms of anxiety, depression, and social isolation , other sTemperament refers to automatic emotions and responses thought to be moderately heritable, therefore largely genetically based . Among tCharacter is largely environmentally derived and responsive to learning and maturation. Among the character dimensions, Self-directedness (SD) measures differences in individual’s executive functions. Highly self-directed persons are described as mature, strong, self-sufficient, responsible, reliable, goal-oriented, constructive, and well-integrated individuals when they have the opportunity for personal leadership. They have good self-esteem and self-reliance. On the other hand, individuals who are low in self-directedness are described as immature, weak, fragile, blaming, destructive, ineffective, irresponsible, unreliable, and poorly integrated when they are not conforming to the direction of a mature leader. They are frequently decsribed by clinicians as immature or having a personality disorder ,10. LoweAlthough it is considered that emotional factors have obvious role in the formation, maintenance and exacerbation of psychosomatic skin diseases, personality profile that shows the basic building blocks of these cases, has not been studied enough. To our knowledge, there is one study on this issue in the patients diagnosed with PFH . In KaraThe review of studies on other psychosomatic skin diseases, which used Temperament and Character Inventory (TCI) revealed contradictory results. Kılıç et al. found higher Harm Avoidance scores and lower Self-directedness scores in patients with psoriasis than healthy controls . In contAlthough this study excluded the patients with a psychiatric diagnosis (since it was a requirement for the diagnosis of PFH), it is a significant deficiency of the study that the level of depression and anxiety symptoms of the patients was not measured and so that the relationship between these symptoms and temperament-character properties was not evaluated. Moreover, since it is a cross-sectional study, the findings are not sufficient to establish a cause and effect relationship.pathophysiology of PFH, all emphasis is on “abnormal or exaggerated central response to normal emotional stress”. Mental reflection of the biological mechanism underlying this might be the personality traits. During the follow-up of these cases, psychiatric evaluation is important and interventions in these areas are required. It is considered that especially psychotherapeutic interventions can increase the chances of success of the dermatological treatments and can have a positive impact on the quality of life and social cohesion of chronic cases. In the future, longitudinal studies containing biological assessments  will provide different and valuable data.To our knowledge, this study is the second one investigating the temperament-character properties in patients with PFH. As a result of the study, it was seen that temperament and character features of PFH patients were different from healthy group and it was considered that these features were affected by many factors including genetic, biological, environmental, socio-cultural elements. During the process of understanding the The authors declare that they have no competing interests.MA have made substantial contributions to conception and design, DD contributed to the acquisition of data, BH conducted the statistical analysis and interpretation of data, and drafting the manuscript and revising, SA, AC and NL contributed to the acquisition of data, and drafting the manuscript. All authors read and approved the final manuscript.


Significant nitric oxide (NO) production was evidenced in the N2-fixing nodules suggesting that it may impact the symbiotic process. Indeed, NO was shown to be a potent inhibitor of nitrogenase activity and symbiotic N2 fixation. It has also been shown that NO production is increased in hypoxic nodules and this production was supposed to be linked – via a nitrate/NO respiration process – with improved capacity of the nodules to maintain their energy status under hypoxic conditions. Other data suggest that NO might be a developmental signal involved in the induction of nodule senescence. Hence, the questions were raised of the toxic effects versus signaling/metabolic functions of NO, and of the regulation of NO levels compatible with nitrogenase activity. The present review analyses the different roles of NO in functioning nodules, and discusses the role of plant and bacterial (flavo)hemoglobins in the control of NO level in nodules.The interaction between legumes and rhizobia leads to the establishment of a symbiotic relationship characterized by the formation of new organs called nodules, in which bacteria have the ability to fix atmospheric nitrogen (N NO prodrhizobia . The intactivity . As nitr nodules . Thus, nng cells . NO was aponicus , and indaponicus . Interesaponicus .Sinorhizobium meliloti in culture  in the control of NO levels in nodules.The chemical nature, concentration, and location of NO might influence its biological role, and at high local concentration NO can become very toxic. NO was thus shown to inhibit the growth of  culture , and the legumes . However legumes , or to htabolism  in functFigure 1). Some studies argue in favor of the involvement of a NO synthase (NOS)-like enzyme. Thus, in Lupinus albus nodule extracts, NO and L-[14C] citrulline were found to be produced in an L-arginine-dependent manner, and the production of L-citrulline was inhibited by a NOS inhibitor , a NR inhibitor. In addition, nodules obtained with plant NR RNA-interference (RNAi) double knockdown (MtNR1/2) exhibited reduced NR activities and NO production levels. The reduction of NO production was reversed by nitrite addition, both in the Tg-treated nodules and in MtNR1/2 RNAi nodules, indicating that NO synthesis depends on NR activity, but that NR does not produce NO directly. The inhibition of NO production by ETC inhibitors indicated that mitochondrial ETC was the site of nitrite reduction into NO , NO reductase (Nor), and nitrous oxide (N2O) reductase, respectively  mutant affected in NO degradation, exhibited a higher NO content in the nodules and a reduced N2 fixation efficiency as compared to the wild type (WT) strain , led to increased N2 fixation efficiency  strain . Such efficiency .S-nitrosylation, which emerges as a key post-translational modification in plants and a pivotal mechanism to mediate NO bioactivity .Nitric oxide is known to modify proteins through activity . Nitrogeon sites  and, int nodules . This suectively . These oS. meliloti hmp mutant, hmp in nodules leads to a significant delay in nodule senescence, and partly relieves dark-induced senescence of the nodules. These results and others : (1) the reduction of nitrate to nitrite by NR, (2) the translocation of nitrite from the cytosol into the mitochondria, (3) the reduction of nitrite in NO, via the mitochondrial ETC, allowing respiration and ATP regeneration, and (4) the diffusion of NO from the matrix to the cytosol, where it is oxidized in nitrate by ns-Hb. Thus, under hypoxic conditions, by reducing nitrite to NO, plant mitochondria preserve the capacity to oxidize external NADH, and retain a limited power for ATP synthesis complementing glycolytic ATP production  activity. It has been shown that the M. truncatula cytosolic GS1 activity is modulated by NO-mediated tyrosine nitration  cycle, glycolysis, and N2 assimilation from either the plant or the bacterial partner .On the other hand, during the Nitration . AccordiLotus japonicus nodules, high concentrations of NO inhibit N2 fixation, while low concentrations of NO enhance it  elicited nodules on M. truncatula roots with higher levels of NO, lower N2 fixation efficiency and earlier nodule senescence than the WT  and NO appears to be a metabolic and signaling key to decipher symbiosis regulation. Peroxynitrite, which is formed when NO reacts with proteins . Since b nodules , it is c nodules . The rec nodules , provideenylated  suggestienylated  could beThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Current evidence on the root-causes of deaths among children younger than 5years is critical to direct international efforts to improve child survival, focus on health promotion and achieve Millennium Development Goal 4. We report a hospital-based estimate for 2005-2007 of the major causes of death in children in this age-group in south-west Nigeria.We used retrospective data from the intensive care unit of a second-tier health facility to extract the presenting complaints, clinical diagnosis, treatment courses, prognosis and outcome among children aged 6—59months. SPSS-19 was used for data analysis.Of the 301 children  admitted into the ICU within the period of study, 173 (26%) presented with complaints related to the gastrointestinal system, 138 (21%) with respiratory symptoms and 196 (29%) with complaints of fever. Overall, 708 investigations were requested for among which were full blood count  and blood slides for malaria parasite . Infection ranked highest  in clinicians’ diagnosis, followed by haematological health problems  and respiratory illnesses . There were negative correlations between outcome of the illness and patient’s weight  and a strong positive correlation between prognosis and outcome of admission . Of the 59 (20%) children that died, presentation of respiratory tract illnesses were significantly higher in females (75%) than in males (39%)  and diagnoses related to gastrointestinal pathology were significantly higher in males (18%) than in females (0%) . Majority of the deaths (21%) occurred among children aged 1.0 to 1.9years old and among weight group of 5.1-15.0kg.The major causes of deaths among under-five years old originate from respiratory, gastrointestinal and infectious diseases – diseases that were recognized as major causes of childhood mortality about half a century earlier. Realization of MDG4 - to reduce child mortality by two-thirds – is only possible if the government and donor agencies look beyond the health sector to find hidden causative factors such as education and housing and within the health sector such as vibrant maternal, new-born, and child health interventions. Statistics detailing infant and child mortality, especially in sub-Saharan Africa (SSA) are staggering. Though child mortality has been declining worldwide as a result of socioeconomic development and implementation of child survival interventions, yet 8·8 million children die every year before their fifth birthday . GloballDisadvantaged children – economically disadvantaged and medically underserved or those that are difficult-to-contact and living in hard-to-reach locations – may face many obstacles to accessing and receiving effective health services such as health promotion, disease prevention, early detection and high-quality medical treatment . ChildreNigeria, located in the West Africa, between Benin Republic to the west and Cameroon Republic to the east has a population of about 156 million. It has six geopolitical zones and 36 States including the Federal Capital Territory. It has a total area of 923,770 sq. km of which land covers 910,770 sq. km, a coastline stretching 853km with two principal rivers – Niger and Benue – merging at about mid country and emptying into the Gulf of Guinea, further south. The climate varies between equatorial in the south, tropical in the centre and arid in the north. Southern lowlands merge into central hills and plateau with mountains in the south-eastern part and plains further north. The vital statistics of Nigeria are still a concern to the government and the international community with an Infant Mortality Rate (IMR) of 75 per 1000 live births, Under-five Mortality Rate (U5MR) of 140 per 1000, Maternal Mortality Rate (MMR) of 704 per 100,000 and Crude Death Rate of 14 per 1000. This worrisome statistics accrue from prevalence rate of malaria being 1858 per 100,000, diarrhoea at 896 per 100,000, pneumonia at 208 per 100,000 and measles at 141 per 100,000. Life expectancy at birth is 52.2 years .Lagos State, with a daytime population of about 14 million , forms one of the 36 States and Federal Capital Territory that constitute Nigeria. The state has a free malaria treatment programme initiated over 10 years ago which has not been evaluated since inception. The health facility where this survey took place is located on Lagos Island and has been described elsewhere . The heaThis is a health facility-based retrospective case review of records kept at ICU. Individual ICU admission case file for the reference period (Mar 2005-Feb 2007) were identified and retrieved. Information retrieved into this form included patients hospital number, date of admission, patients biodata, presenting complaints, clinicians’ diagnosis, investigations requested for, prescribed medications and/or procedures, prognosis of the illnesses, outcome and duration of admission.Statistics of childhood mortality is worrisome to government and parents are perplexed about the reasons and causes of children dying before they are five years old. Lack of consideration for and responsiveness to social determinants of health may be responsible for high childhood mortality rate in Nigeria. Nigerian government should emulate the OECD countries and some oil-rich Arab nations in addressing health by reducing health inequity and inequality from the perspective of social determinants of health. This study attempts to produce a league table of major diseases which kill under-fives in south-west Nigeria but which can be easily prevented not by expensive biomedical imagination but by easily affordable health promotion. This will catapult the nation to a rapid progress towards the achievement of MDG 4 by 2015. Otherwise, Nigeria, unlike some other sub-Saharan countries, may not readily achieve this global target on time.Since most health sector plans have not yielded results fast enough, then, what definitive strategy has to be in place to reduce childhood mortality in Nigeria fast enough to attain MDG4 by 2015?This study is limited to Nigerian children under the age of five who were admitted into the intensive care unit of a second-tier paediatric hospital in Lagos.Necessary Ethics Committee approval of the Lagos State Health Management Board, Campbell Street, Lagos, Nigeria was secured before carrying out this study. Informed consent was obtained from care-givers where feasible or from representatives of subjects of the study.Two data collectors were recruited to retrieve data from the hospital medical records. A pro-forma data record form was designed for transcription of data from the medical records. Data were collected over a 3-month period and simultaneously transcribed verbatim into the data record form after close inspection.T-test (2-tailed) and significance level was set at ≤0.05. Differences were considered significant when p was ≤0.05. Tables, charts and graphs were used to present data.Data of each child was coded for anonymity, ease of reference, avoidance of bias and fed into a lap top computer, cleaned and cross-checked for errors. Analysis of the cleaned data was done using Statistical Package for Social Sciences version 19 for Windows software. For easier analysis, age (years) was grouped (age group) into four categories viz. (i)1-1.9, (ii) 2-2.9, (iii) 3-3.9 and (iv) 4-4.9; weight (kg) was categorized into (i) ≤5 (ii) 5.1-10 (iii) 10.1-15 and (iv) 15.1-20. Diagnosis of illness entities was coded from 1-11 where 1=respiratory, 2=hematology, 3=gastrointestinal, 4=nutritional, 5=malaria, 6=measles, 7=cardiac, 8=nervous, 9=meningitis, 10=septicaemia and 11=others. Prognosis was coded into 1=good, 2=fair, 3=poor, 4=very poor and 5=very, very poor. Outcome of admission into ICU was graded in a scale of 6 where 1=full recovery and discharged home, 2=absconded, 3=referred to another health facility, 4=discharged against medical advice (DAMA), 5=still on admission and 6=patient died. Morbidity and mortality data were analysed descriptively obtaining frequencies and percentages, and inferentially using chi-square test to determine associations, where appropriate. A p-value ≤0.05 was regarded as significant. Pearson’s coefficient of correlation (r) was determined for all normally distributed variables while Spearman’s correlation coefficient was determined for variables without normal distribution. Gamma value was used to determine strength and association of ordinal data on a Likert scale. The significance of association/correlation was determined by student’s Medical records of 301 children  who were admitted into the intensive care unit (ICU) of a second-tier paediatric health facility between March 2005 and February 2007 were reviewed.Table Table Of the 587 diagnoses made by the attending clinicians Table , diagnosTable Table Prognostic values ranged mainly from poor to very poor across all age groups. Table The outcome of admissions into the ICU for all the children in different age groups and gender is as indicated in Table Table and child) mortality and longer life expectancy [The poor health outcomes in Nigeria mainly stem from a lack of appropriate targeting strategies for reaching poor and under-served populations and low levels of public funding . Historipectancy . It is opectancy . The betpectancy . Nigeriapectancy , an obsepectancy . For exapectancy . The Worpectancy  excludinThe National Health Insurance Scheme (NHIS), officially launched in the country in June of 2005, is worth mentioning here. NHIS was expected to boost funds flowing into the healthcare sector in which workers pay up to 5% of their salary into the scheme in order to qualify for free treatment for themselves, a spouse and up to four children. In the end, poor planning, lack of research to provide evidence-based infrastructure as well as lack of accountability spelt the doom of NHIS, as there was no particularly viable health scheme for the teeming population of Nigerians not working for the government. Despite being relatively rich compared with other countries in sub-Saharan Africa in terms of per capita GDP, Nigeria spends a significantly lower share on social protection, less than 1% in 2006-2007; Ethiopia, Kenya, Malawi, Mozambique and Uganda spent an average of 1.4% in the same year .What could have been done to save the children? The answer lies beyond health reforms and extends into government policies on housing, roads, provision of basic amenities, adequate transportation, mechanized agriculture and elimination of health inequity. Factors such as growing income inequality, economic and social dislocations caused by internal conflicts, relative shortage of social and economic infrastructure in rural areas, low productivity especially agriculture, migration of the educated work force from the rural to the urban areas and the brain-drain syndrome may directly or indirectly contribute to the observed high child mortality. Government hospitals should emulate their North or South African counterparts to adequately provide for those children (and adults) who would require intensive care; but more especially, government should focus more attention on its social policies. This emphasizes that reform in Nigeria’s health care delivery, access and funding are certainly needed. Meaningful improvement in population health may require the country to invest as heavily in social programs as the Scandinavian countries. Social policies that care for people are the best investments for health  and inveThis study has its own limitations. First, data that were analyzed were collected retrospectively, therefore the accuracy of these data cannot be fully ascertained, though there is a high index of credibility that they were recorded according to the events that took place at the ICU when the children were admitted. Secondly, the instrument for collecting the data were not standardized according to Cronberg’s alpha. Thirdly, causes of deaths were not categorized according to the International Classification of Diseases, 10th revision . Fourth, criteria for prognostic differentiation of the children were not defined. Fifth, the result from the study may not be generalized to the entire population of Nigeria. Sixth, exact causes of death of the study children were not determined and finally, though the study was not particularly on social determinants of health, inferences were made to them.Child mortality is still high in Nigeria. The government should set up a body of researchers to critically appraise social determinants of health and health inequity. A lot still has to be done to ameliorate the incessant onslaught of the negative outcomes associated with social determinants of health and health inequity for the country to join the league of healthy nations.The Federal Government of Nigeria is doing all things possible to improve the health of its people. In furtherance to this, it should establish the Healthy People 2015 Initiative as a goal towards the elimination of health disparities among Nigerians. In addition, the government should make a large investment in research into the health disparities and health equity, targeting multi-agency collaboration which should include representatives of Civil Society Organization and Labour Congress. There is a need for more innovative approaches derived from trans-disciplinary research and involving multiple Federal Ministries and different disciplines such as Health, Finance, Women Affairs, Water Resources, Communication, Transportation, Environment, Youth and Social Services and others. Also, the Federal Ministry of Health, as a matter of urgency, should establish Health Promotion Division to be headed by a professional in this area. State Ministries of Health should also emulate this planned suggestion.The authors declare that they have no competing interests.BMA and CC conceptualized the study and organized the analytic plan. AE supervised all aspects of data collection and implementation of the study. BMA, AE and DD conducted the analyses. BMA led the writing and all authors contributed to the interpretation of the findings and the writing. All authors read and approved the final manuscript.Bamgboye M. Afolabi is the Chief Executive Director of Health, Environment and Development Foundation, a Non-Governmental Organization with its office in Lagos Nigeria, Cecilia Clement is with the Department of Morbid Anatomy, Lagos University Teaching Hospital, Idi-araba, Lagos; Adejuwonlo Ekundayo is the Director of Silverwood Consult, a Research and Development outfit in Lagos, Nigeria and Duro Dolapo is with the Support for National Malaria Program (SuNMaP), Abuja, Nigeria.


MDFT  is a family based outpatient treatment programme for adolescent problem behaviour. MDFT has been found effective in the USA in adolescent samples differing in severity and treatment delivery settings. On request of five governments , MDFT has now been tested in the joint INCANT trial  for applicability in Western Europe. In each of the five countries, study participants were recruited from the local population of youth seeking or guided to treatment for, among other things, cannabis use disorder. There is little information in the literature if these populations are comparable between sites/countries or not. Therefore, we examined if the study samples enrolled in the five countries differed in baseline characteristics regarding demographics, clinical profile, and treatment delivery setting.INCANT was a multicentre phase III(b) randomized controlled trial with an open-label, parallel group design. It compared MDFT with treatment as usual (TAU) at and across sites in Berlin, Brussels, Geneva, The Hague and Paris.Participants of INCANT were adolescents of either sex, from 13 through 18 years of age, with a cannabis use disorder (dependence or abuse), and at least one parent willing to take part in the treatment. In total, 450 cases/families were randomized  into INCANT.We collected data about adolescent and family demographics . In addition, we gathered data about problem behaviour .cross-site differences on many variables. Most of these could be explained by variations in treatment culture, as reflected by referral policy, i.e., participants' referral source. We distinguished 'self-determined' referral (common in Brussels and Paris) and referral with some authority-related 'external' coercion (common in Geneva and The Hague). The two referral types were more equally divided in Berlin. Many cross-site baseline differences disappeared when we took referral source into account, but not all.There were no major differences on any of these measures between the treatment conditions (MDFT and TAU) for any of the sites. However, there were A multisite trial has the advantage of being efficient, but it also carries risks, the most important one being lack of equivalence between local study populations. Our site populations differed in many respects. This is not a problem for analyses and interpretations if the differences somehow can be accounted for. To a major extent, this appeared possible in INCANT. The most important factor underlying the cross-site variations in baseline characteristics was referral source. Correcting for referral source made most differences disappear. Therefore, we will use referral source as a covariate accounting for site differences in future INCANT outcome analyses.ISRCTN51014277ISRCTN:  In 1999, the (junior) Ministers of Health of Belgium, France, Germany, the Netherlands, and Switzerland agreed that their countries were disputing each other's cannabis policies without having enough data to support any stance. They wished to combine scientific efforts. The Five-Countries Action Plan for Cannabis Research from April 2003 stressed the need of a transnational trial to test an outpatient treatment of cannabis use disorder and associated problems  among youth in the five Western European countries mentioned [MDFT is a family based outpatient treatment programme for adolescent problem behaviour [1 - 4]. Key to MDFT is the assumption that each major domain in the life of an adolescent may contribute to the incidence and persistence of behavioural problems (through risk factors) and may help in resolving such problems (through protective factors). The life domains include the youth itself, parent, family, friends and peers, school and work, and leisure time. In 5 to 7 months, the therapist carries out, in rapid succession, therapy sessions with the adolescent alone, with the parents alone, with the family (youth and parents), and sometimes with representatives from systems outside the family  present. The therapist sets out to improve life domain conditions for the adolescent and the family in an outreaching fashion. MDFT views family functioning as instrumental in creating new, developmentally adaptive lifestyle alternatives for the adolescent. Skills training includes substance use relapse prevention, family communication, and parenting.MDFT has been tested with success in different adolescent populations, doses and treatment delivery settings in the USA ,4.Hurdles had to be overcome before the INCANT trial could start. A RCT was controversial in Western European youth care at the time. It was feared that a standardized  time-limited treatment like MDFT would not be accepted in France, with its dominant psycho-analytic treatment tradition or in Germany (Berlin), where treatment of substance abusing adolescents often lasted for more than 1 year. Further, Swiss clinicians believed that coercing adolescents into treatment, which was deemed feasible in INCANT, would fail to convince cases to accept or complete treatment. Nevertheless, we managed to mount the INCANT study.http://www.consort-statement.org). However, this does not apply to multisite trials such as INCANT. INCANT succeeded in randomizing study participants on a number of stratification variables, but one set of variables could not be included in the randomization process: the local treatment culture in a city/country, and the local referral and other treatment-related policies. Therefore, we performed statistical analyses to assess the INCANT sites from the five countries on comparability of study participants' baseline characteristics.The process of randomization ensures that study groups - i.e., the MDFT and TAU groups - are equivalent on baseline characteristics. CONSORT, which is the opinion leading Consolidated Standards of Reporting Trials group, finds it illogical, but not wrong, to test for statistically significant differences between trial groups at baseline, because by definition any difference found is due to chance rather than the result of a factor causing variation between groups  randomized controlled trial with an open-label, parallel group design. This study compared MDFT with TAU at and across sites in Berlin, Brussels, Geneva, The Hague and Paris. Part of TAU in Paris was specified in a treatment manual and was called TAU-e (e = explicit). In this paper, we combine TAU-e and TAU under the term 'TAU'; the distinction between the two treatment variants will feature in other publications. Assessments were carried out at baseline (immediately before randomization) and at 3, 6, 9 and 12 months after randomization. Before the trial started, INCANT was approved by all relevant ethical boards  = 20.6, p < 0.001), being lowest in The Hague and Paris, where approximately 25% presented with the milder diagnosis 'abuse'.The rate of cannabis dependence differed between sites . These disorders were common, except in The Hague (16%) and Paris (30%).Alcohol abuse and alcohol dependence are combined as 'alcohol use disorders' in Table Many adolescents had experience with other drugs, but not on a regular basis. For no class of drugs other than cannabis, substance use disorder rate exceeded the 5% level at any site.χ2  = 22.7, p < 0.001), with arrest rate being lowest in Berlin (20%) and The Hague (28%) and highest in Geneva (50%).Across sites, 34% of the adolescents had been arrested once or more in the 90 days preceding the baseline assessment Table . Sites dMore than one reason of arrest could be listed per case. Arrests were mostly for drug offenses, property crimes and violence, but this differed between sites. Of the arrested youth in Brussels, 23% were charged for a drug offense and in Paris and Geneva close to 40%. The figure for Berlin was 8% and for The Hague 1%. Other reasons of arrest varied between sites as well. Of Swiss arrested adolescents, 30% had been booked for property crimes, as compared with approximately 10% of Belgian, German and Dutch teenagers, and with a low of 2% in Paris. Violent crimes accounted for 8% - 20% of adolescents who had been arrested, with Paris again being the lowest ranking site (2%).F  = 6.4, p < 0.001. Internalizing problems: ANOVA, F  = 2.3, p = 0.06. Youth in Berlin reported higher levels of externalizing symptoms than youth in The Hague and Paris, and youth in Geneva reported higher levels than youth in Paris . Contact with alcohol misusing peers also varied between sites , and was most frequent in The Hague (99%) and lowest in Brussels (52%). Having delinquent friends was highest in The Hague (95%) and lowest in Paris (62%), with a significant difference across sites .Across sites, 88% of the adolescents said they had one or more friends with a drug problem . Lower and middle education prevailed in Berlin (56%), Brussels (63%), The Hague (70%), and Paris (63%). This figure was lowest in Geneva (47%).Most adolescents were still in school Table , though χ2  = 158.4, p < 0.001), with those having paid work (mostly jobs on the side) being most prevalent in Brussels and The Hague and least in Paris. Of the French adolescents, 91% said they were not looking for paid work - much more than at the other sites. The Hague scored lowest on this measure, with 18%.Having a job and pursuing employment varied across sites. We took together the youth with a regular and with a temporary job Table . Sites dχ2  = 18.1, p = 0.02). Table Parents of 39% of all families were still together, but most so in Paris (53% of families) and least in Berlin (28%) .We asked the adolescents to report on problems experienced by their parents and siblings. Overall, about 30% of the youth stated that one or both parents had mental health or addiction problems, with the highest proportion being noted in Berlin (41%) and the lowest in Paris (17%). Alcohol problems were the most prevalent of the three issues surveyed . The parent having the problem differed across sites, with fathers being more prevalent as 'problem owner' in Brussels, Geneva, and The Hague, and mothers in Berlin and Paris. A smaller proportion of parents reportedly had a history of legal problems (14%), with Paris at the bottom of the list (5%). Parents with a history of legal problems significantly differed across sites . Self-referral and referral by family and friends were more common in Brussels and Paris than in Berlin and The Hague, where referral by other treatment and care agencies carried more weight, and in Geneva with its high proportion of referral by Justice-related institutions.As seen in Table χ2  = 167.1, p < 0.001).In Table p > 0.7).Referral source and SD/EC distinction were similar for treatment conditions (MDFT and TAU) at all sites  and in demographic characteristics (type of school attended) were no longer significant.F  = 2.6, p = 0.04). Berlin youth reported more externalizing symptoms than youth in The Hague and Paris did, and youth in Geneva reported more than youth in Paris.However, accounting for referral source did not fully redress differences in adolescent reports of externalizing symptoms . Subsequent univariate tests showed that, in addition to the variable 'externalizing symptoms' just mentioned, sites also differed in frequency of adolescent substance use  when the TLFB, YSR and CBCL measures were considered together, with Swiss youth reporting significantly less substance use than adolescents at the other sites.We also performed a multivariate analysis of variance (MANOVA) for three intended outcome measures  together, to examine the extent to which referral source accounted for site differences when considering variables combined. The result of the multivariate test was significant . In Geneva and The Hague, detention and other justice-imposed measures are common and this was reflected in a higher rate of coerced referral. This is not to say that, for instance, the Dutch adolescents were more delinquent or more strongly disordered than at the other sites. Detaining youth is much more common in the Netherlands (and Switzerland) than in the other INCANT countries . The domStudy site populations were similar in many respects, but nevertheless had distinct profiles. Take the example of The Hague. The Dutch teenagers more often had friends with a substance use or criminal behaviour problems than at the other sites. Still, when examining overall clinical severity, the Dutch adolescents were not as impaired as youth at some other sites. The rate of cannabis dependence and the rate of alcohol use disorders were lowest in The Hague and Paris. The frequency of self-reported internalizing and externalizing symptoms, as well as arrest rates, were also low. Most Dutch teenagers had an income from a job or other employment, which may have kept them engaged in activities that competed with time that could otherwise have been spent using drugs or associating with delinquent peers.The adolescent study population in Paris also presented with less impairment than youth in Berlin, Geneva, and Brussels. Cannabis dependence and alcohol use disorder rates were relatively low among French youth, as were the rates of externalizing symptoms and arrests. Most teenagers of the Paris site were not looking for work, but were well provided for by their affluent families.The populations in Berlin, Brussels and Geneva scored higher than those from The Hague and Paris on cannabis dependence, alcohol use disorders, and externalizing symptoms. Parent divorce/separation rate was highest in Berlin; the proportion of parents with legal problems was highest in Brussels. Recent justice involvement was highest among Geneva youth.We compared sites from five European countries. The data collected pertain to these sites, but not necessarily to the country where a site was located. What is true in Berlin or Paris, for instance, may not be true in all of Germany or France, respectively. A city does not represent the countryside. One site in a (semi-)federal state, such as Belgium, Germany and Switzerland, does not stand for the country as a whole. Therefore, all conclusions in this paper are restricted to the sites selected for INCANT, so do not extend to other sites.When five European governments are interested in having a treatment tested for adolescents with cannabis use disorder, as in our case, it would not be efficient to carry out five separate trials. A multisite trial has the advantage of having increased statistical power, and of being more relevant for practice  than a stringently controlled local trial would be. However, a multisite trial also carries risks, the most important one being lack of equivalence between local study populations. Our site populations differed in many respects.Variations between local study populations are not an insurmountable barrier for pooling data across sites, if they somehow can be accounted for ,8. This An alternative approach for dealing with multisite issues may be treating site as a random effect . HoweveOur experience with a transnational trial in an area with such a limited history of experimental studies was satisfactory. It appeared possible to include sites from different European countries, with different treatment systems and policies, into one meaningful cross-national RCT. We gained more insight into the applicability of MDFT in practice than would have been possible in stand-alone studies. As next papers will show, the cross-national study design did not stand in the way of demonstrating the effectiveness of MDFT; on the contrary. Multisite trials are a recommendable option, provided each site recruits a sufficient number of cases to allow for local analyses if sites appear to differ on unexplainable grounds.ADI: Adolescent Diagnostic Interview; ANOVA: analysis of variance; CBCL: Child Behavior Checklist; CEDAT: Conseils Aide et Action contre le Toximanie; CTRADA: Center for Treatment Research on Adolescent Drug Abuse; EC: externally coerced referral; INCANT: International Cannabis Need of Treatment study; IQ: intelligence quotient; MANOVA: multivariate analysis of variance; MDFT: Multidimensional Family Therapy; Sd: standard deviation; SD: self-determined referral; TAU: Treatment As Usual; TAU-e: manualized TAU in France (e = 'explicit'); TLFB: Timeline Follow-Back; YSR: Youth Self ReportAll authors declare that they have no competing interests.OP, GH and HR were substantially involved in the conception of the study. HR designed and coordinated the overall study, with statistical advice from GH, whereas OP set up and directed the study in Paris. OP, GH, and HR all had a major part in the statistical analyses and the interpretation of the results, and in drafting the present publication. CS, MT, RR, TA and PW helped in recruiting study participants, administered the questionnaires and interviews at baseline and follow-up, guarded follow-up completion rates, and entered all data into the INCANT database. All have approved the present publication.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/11/110/prepub


However, NSTEMI hospitalization percentages were similar over the 10-year period. The hospitalization age for AMI, STEMI, and NSTEMI was increased over the 10-year period by 14, 9, and 7 years in male, and by 18, 18, and 21 years in female. The female and male hospitalization cost and lengths were similar in the period. As compared to nonmedical center, the hospitalization cost for STEMI in medical center was higher in male patients, but not in female patients, and the hospitalization cost for NSTEMI was higher in both male and female gender. We found significant differences between male and female, medical center and non-medical center, or STEMI and NSTEMI on medical care over the 10-year period.It is not clear whether gender is associated with different hospitalization cost and lengths for acute myocardial infarction (AMI). We identified patients hospitalized for primary diagnosis of AMI with (STEMI) or without (NSTEMI) ST elevation from 1999 to 2008 through a national database containing 1,000,000 subjects. As compared to that in 1999 Acute myocardial infarction (AMI) is one of the most important cardiovascular diseases with large medical expenditures. Decreased occurrences of AMI have been demonstrated epidemiologically , 2. ThroGender differences play an important role in the pathophysiology of AMI. Although coronary plaque rupture with acute thrombosis formation is common pathophysiology for men and women, women are usually older than men and associated with a low incidence of AMI, but with a higher mortality –16. It hThis study used the nationwide inpatient data from NHI, which can provide the database including the medical expenditure, admission periods, and co-morbidities , 18. Thet-test, one-way analysis of variance (ANOVA), or two-way ANONA with post hoc of Fisher's method. Categorical variables were reported as frequencies and compared using a  x2 or Fisher exact test if at least one cell had an expected cell count below 5. A two-tailed probability of P < 0.05 was considered statistically significant. All statistical analyses were performed with SPSS (version 13.0) or SigmaStat (version 3.5).Continuous variables were expressed as mean ± standard deviation (SD). Gender differences, medical center and non-medical center differences, and lower and higher hospitalization cost differences were compared by using unpaired Student's P = 0.061) older than male patients in 2007~2008. As shown in We compared the average hospitalization cost over the 10-year period and found that the hospitalization cost of total, male, and female AMI was not significantly changed over the 10-year period . HoweverP = 0.07). The hospitalization lengths of total STEMI were longer in medical center than in non-medical center, but were not significantly different in male (P = 0.06) or female (P = 0.11) patients. In NSTEMI, the hospitalization cost of total, male, and female patients was larger in medical center than in non-medical center. The hospitalization lengths of total (P = 0.09), male (P = 0.18), and female (P = 0.29) patients were similar between medical center and non-medical center. The hospitalization age of AMI and STEMI was similar between center and non-center both in male and female gender. However, the hospitalization age of NSTEMI was younger in medical center than in non-medical center. Because the average hospitalization cost from 1999–2008 is close to NT 10670, therefore, we choose this value (10000 NT dollars) for grouping. In this study, through the reliable nationwide population-based dataset, which almost covers entire population in Taiwan, we demonstrated that the hospitalization percentages of AMI and STEMI were declined from 1999 to 2008. In this period, the total admission number was increased, but the number of total AMI or STEMI admission was decreased. Therefore, both factors contribute to the changes of AMI and STEMI admission percentage. The improvement would be caused by more aggressive risk factors control from medical systems and education on AMI prevention from the community and individual [In this study, the patient age of MI with or without ST elevation was significantly increased over the 10-year period. Similar to those in the previous studies, the patient age was older in female than in male, which implies the rather normal coronary artery and healthy life pattern in female than in male with the similar age. The decrease of AMI percentage of hospitalization and patient ages indicates that the improvement in treating coronary artery disease during this period. In contrast, the age of MI was reported to be similar within the 10-year period in USA [In this study, for the first time, we evaluated the hospitalization cost of AMI over the 10-year period. Surprisingly, similar hospitalization cost over the 10-year period for treating MI was observed. Since the budget for health insurance in Taiwan was increased and mild inflation was demonstrated in this period, the similar hospitalization cost for treating MI actually means that the medical fare for MI treatment was decreased in this period. Although the reasons were not clear, cost restrictions from Bureau of NHI in Taiwan may play a role in this finding. In addition, the hospitalization cost may be underestimated since the expenses might not be coved by NHI and will not appear in the data. Additionally, this study also found a trend that the male patients had higher hospitalization cost for MI and STEMI. However, the hospitalization length seems to decrease in 2007~2008. In addition, we found an inverse correlation between the hospitalization length and daily cost. These findings suggest that more aggressive treatment of AMI may shorten the hospitalization length or more examinations and treatment were applied during the initial admission period. Medical centers had better facilities and personal supports for medical care with a large patients and procedure volume. It has been shown that volume of medical care will correlate with the outcome in AMI patients , 21. HowWe compared the differences between higher and lower hospitalization cost over the 10-year period and found that higher hospitalization cost patients were younger with shorter hospitalization lengths, which indicates that more aggressive treatment was used for these patients. However, this finding was mainly found in the male patients with STEMI.Our findings should be interpreted with caution due to the study's limitations. First, we cannot identify whether the patients first admitted to non-medical center and then transferred to medical centers. Second, the results in this study are from the nationwide database, therefore the detail medications and management for these patients were not clear. In addition, the patient's biochemistry, image, and disease severity were not available. Moreover, although these analysis methods were widely used, we cannot exclude the possibility that ICD-9 codes might be incorrectly cited , which mIn conclusion, through the NHI database, we found an improvement of medical care for AMI. There were significant differences between male and female, center and non-medical center, or STEMI and NSTEMI over the 10-year period.