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简介：AbstractBackground:Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs.Methods:In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs.Results:There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment.Conclusions:Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

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简介：AbstractBackground:Cumulative blood pressure (BP), a measure incorporating the level and duration of BP exposure, is associated with the risk of cardiovascular disease (CVD). However, the level at which cumulative BP could significantly increase the risk remains unclear. This study aimed to investigate the association of 15-year cumulative BP levels with the long-term risk of CVD, and to examine whether the association is independent of BP levels at one examination.Methods:Data from a 26-year follow-up of the Chinese Multi-provincial Cohort Study-Beijing Project were analyzed. Cumulative BP levels between 1992 and 2007 were calculated among 2429 participants free of CVD in 2007. Cardiovascular events (including coronary heart disease and stroke) occurring from 2007 to 2018 were registered. Adjusted hazard ratios (HRs) for CVD incidence associated with quartiles of cumulative systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated.Results:Of the 2429 participants, 42.9% (1042) were men, and the mean age in 2007 was 62.1 ± 7.9 years. Totally, 207 CVD events occurred during the follow-up from 2007 to 2018. Participants with higher levels of cumulative SBP or DBP exhibited a higher incidence rate of CVD (P < 0.001). Compared with the lowest quartile of cumulative SBP, the HR for CVD was 1.03 (95% confidence interval [CI]: 0.59-1.81), 1.69 (95% CI: 0.99-2.87), and 2.20 (95% CI: 1.21-3.98) for the second to the fourth quartile of cumulative SBP, and 1.46 (95% CI: 0.86-2.48), 1.99 (95% CI: 1.18-3.35), and 2.08 (95% CI: 1.17-3.71) for the second to the fourth quartile of cumulative DBP, respectively. In further cross-combined group analyses with BP measurements in 2007, 15-year cumulative BP levels higher than the median, that is, 1970.8/1239.9 mmHg·year for cumulative SBP/DBP, which were equivalent to maintaining SBP/DBP levels of 131/83 mmHg or above on average in 15 years, were associated with higher risk of CVD in subsequent years independent of BP measurements at one-time point.Conclusion:Cumulative exposure to moderate elevation of BP is independently associated with increased future cardiovascular risk.

简介：AbstractBackground:Circular RNA (circRNA) is a type of closed circular noncoding RNA (ncRNA), mostly formed by back-splicing or alternative splicing of pre-messenger RNA (mRNA). The aim of this study was to explore the expression profile of circRNA in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and discover potential molecular markers of AS.Methods:The circRNA microarray technology was used to detect the expression of circRNAs in the peripheral blood of 6 patients with AS and 6 healthy controls (HC). To screen the differentially expressed circRNAs by fold change (FC) and P value, these differentially expressed circRNAs were analyzed by bioinformatics. In 60 cases of AS and 30 cases of HC, 4 circRNAs were subjected to real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and their correlation with various clinical indicators was analyzed. Finally, the receiver operating characteristic (ROC) curve was used to analyze their potential as AS diagnostic markers.Results:The microarray results showed that there were 1369 significantly differently expressed (P < 0.05, FC > 1.5) circRNAs between the AS and HC groups (675 upregulated and 694 downregulated). The results of bioinformatics analysis suggested that they were mainly involved in "enzyme binding," "adenosine ribonucleotide binding," "MAPK signaling pathway" , etc. The RT-qPCR results showed that the expressions of hsa_circRNA_001544 (U = 486.5, P < 0.05) and hsa_circRNA_102532 (U = 645, P < 0.05) were significantly different between the AS group and the HC group. The AS group was further divided into two subgroups: active AS (ASA) and stable AS (ASS). After analysis, it was found that compared with the HC group, hsa_circRNA_001544 was significantly increased in both ASA (U = 214, P < 0.05) and ASS groups (U = 273, P < 0.05), while hsa_circRNA_008961 (U = 250, P < 0.05) and hsa_circRNA_102532 (U = 295, P < 0.05) were only significantly increased in the ASA group. Furthermore, hsa_circRNA_012732 was significantly different between the ASA and ASS groups (U = 194, P < 0.05), and there was no statistical significance among the remaining groups. Correlation analysis results showed that hsa_circRNA_012732 was negatively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), high-sensitivity C-reactive protein (hsCRP), and globulin (GLOB) and positively correlated with lymphocyte count (LY), mean corpusular volume, and albumin (ALB), and hsa_circRNA_008961 was negatively correlated with platelet (PLT) count. ROC curve analysis showed that hsa_circRNA_001544 (95% CI = 0.610-0.831, P < 0.05) and hsa_circRNA_102532 (95% CI = 0.521-0.762, P < 0.05) were statistically significant, and their area under curve (AUC) values were 0.720 and 0.642, respectively.Conclusions:There are differentially expressed circRNAs in PBMCs of AS patients, and they may be involved in the occurrence and development of AS. Among these differentially expressed circRNAs, hsa_circRNA_012732 has the potential to become an indicator of disease activity, and hsa_circRNA_001544 has the potential to become a molecular marker for AS diagnosis.

简介：AbstractHepatitis C infection is not uncommon in pregnant women. Vertical transmission of the virus from mother to fetus is estimated at 4%-8%, however this transmission rate is significantly higher when the mother is co-infected with HIV. Intrauterine blood transfusions can be a necessary part of management for certain perinatal conditions like hemolytic disease of the fetus. Currently there is no published material available on the vertical transmission risk of HCV infection to the fetus as a result of this procedure, irrespective of HIV coinfection. We present a case of a pregnant woman co-infected with HCV and HIV that required an intrauterine blood transfusion during pregnancy. Vertical transmission of either infection to the child did not occur. This provides important evidence that vertical transmission of HCV and/or HIV does not necessarily occur with intrauterine blood transfusions.

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简介：AbstractPurpose:Impending compartment syndrome is a common event following closed tibia fractures, which can progress to sinister compartment syndrome. Fasciotomy is the only definitive treatment available, though it has its own drawbacks and complications. Medical management at present consists of limb elevation and adequate hydration. This study aims at determining whether intravenous administration of Mannitol reduced the intracompartmental pressure in patients with closed tibial fractures.Methods:This is a double blinded, randomized control trial done in a single tertiary care center in India. Forty-five patients were recruited between February 2012 and October 2012. Forty patients who presented to the emergency department with isolated, closed, high velocity, and proximal 2/3 tibia fractures were included in this study. Patients with contraindication to Mannitol were excluded. They were allocated into 2 groups by the investigator using computer generated randomization. The pressure in the anterior compartment of the leg was measured with a handheld Stryker pressure monitor. Then either 20% Mannitol or 0.9% normal saline as given intravenously in a blinded manner, based on the randomization. The intracompartmental pressure was measured at 0, 1 and 3 h after the infusion. The participant, investigator and statistician were masked to the group assessment.Results:There was no difference in intracompartmental pressures at 1 or 3 h, between the groups. However, in patients with the baseline of compartmental pressures ≥30 mmHg, Mannitol showed a marked reduction in pressure of 8.5 mmHg at 1 h compared to almost no change in pressure in the saline group. There were no adverse events with the use of Mannitol.Conclusions:This preliminary study appears to show that Mannitol is useful in the management of the increased compartment pressure. The limitations of this study were that it only involved a small group of patients and the baseline pressures in both the groups were not comparable. More studies are required before the use of Mannitol as a standard of care in the management of compartment syndrome can be established.

简介：AbstractObjective:To evaluate the predictive ability of neonate condition through the traditional parameters and artery umbilical cord blood gas (aUCBG).Methods:A prospective cohort study was conducted in obstetrics and gynecology department between October 2017 and August 2018 at Tongji Hospital in Wuhan, China, and 360 aUCBG samples were collected. The average age of pregnant women was (29.50±4.42) years, range from 19 to 48 years old. The gestational age range from 28+4 weeks to 41+3 weeks at admission. Logistic regression and area under the curve (AUC) from Receiver operating characteristic curves were used to identify risk factors, such as, premature rupture of membranes (PROM), high blood pressure, premature delivery (PD), low 1-minute Apgar scores (Apgar 1), low 5-minute Apgar scores (Apgar 5), pH, base excess, bicarbonate, neonatal blood sugar (NBS), and so on, to predict neonatal condition and evaluate the predictive ability of traditional and aUCBG parameters.Results:In all cases, PROM, PD, Apgar 1, Apgar 5, pH, base excess, bicarbonate, total carbon dioxide, and neonatal blood sugar were risk factors and were associated with poor condition of neonate. Apgar 1 were an independent risk factor. Combined traditional and aUCBG parameters had higher AUC of 0.895 (95% confidence interval (CI): 0.830-0.960, P<0.001). In cesarean section subgroup, high blood pressure, PD, and Apgar 1 were risk factors and were associated with poor condition of neonate. Apgar 1 and low pH were the independent risk factors. Combined traditional and aUCBG parameters had highest AUC of 0.940 (95% CI: 0.886-0.993, P<0.001). In vaginal delivery subgroup, maternal age above 35 years, PROM, PD, Apgar 1, Apgar 5, and male newborn were risk factors and were associated with poor condition of neonate. Maternal age above 35 years was an independent risk factor. Combined traditional and aUCBG parameters had highest AUC of 0.897 (95% CI: 0.828-0.965, P<0.001). For pregnant women without comorbidities and complications of pregnancy, aUCBG may not be necessary.Conclusion:In high-risk pregnancies, especially lower Apgar scores, PD, and maternal age above 35-year old, aUCBG is recommended. Traditional parameters combined with aUCBG might increase the predicting ability of neonate condition.

简介：AbstractBackground:Acute mural dissection of the anterior wall of the internal carotid artery which may contribute to the development of blood blister-like aneurysms (BBLAs) was postulated, and stenting or flow diversion treatment across the soi-disant aneurysm was reported in this study.Methods:From December 2016 to December 2018, 8 patients presenting with subarachnoid hemorrhage (SAH) due to BBLA were subjected to endovascular treatment with stent-assisted coiling. Clinical outcomes were evaluated using a clinical outcome score scale.Results:Based on angiograms, pathologic change involving the supraclinoid segments of the internal carotid artery (ICA) adjacent to BBLA was found in all patients. This pathologic change meant a focal dissection of the supraclinoid segment of the ICA which constituted the pathogenesis of BBLAs. Closed-cell, open-cell, and braided stents were used in 1, 1, and 6 patients, respectively. Complete obliteration was achieved following endovascular treatment among all 8 patients harboring BBLA. One re-bleeding successive to a closed-cell stent across the aneurysmal neck was observed. Follow-up angiograms revealed stable complete exclusion of all BBLAs from the parent vessel at 3 to 8 months. All patients had a favorable clinical outcome score of 0-1.Conclusions:Acute dissection of a focal point of the intracranial vessels underlies the development of BBLAs. Open-cell and braided-cell stent-assisted coiling may constitute appropriate treatment due to good apposition against the vascular walls. Adjunctive coils may facilitate immediate complete occlusion of BBLAs.

简介：AbstractBackground:China has experienced rapid urbanization in the past 30 years. We aimed to report blood cadmium level (BCL) in the rapidly urbanized Yangtze Plain of China, and explore the association between BCL and 25-hydroxyvitamin D (25(OH)D).Methods:Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cross-sectional study (ChiCTR-ECS-14005052, www.chictr.org). We enrolled 3234 subjects from 12 villages in the Yangtze Plain. BCLs were measured by atomic absorption spectrometry. 25(OH)D was measured with a chemiluminescence assay.Results:A total of 2560 (79.2%) subjects were diagnosed with vitamin D deficiency. The median (interquartile range) BCL was 1.80 μg/L (0.60-3.42) for men and 1.40 μg/L (0.52-3.10) for women. In women, mean 25(OH)D concentrations were inversely associated with BCL (0.401, 95% confidence interval: -0.697 to -0.105 nmol/L lower with each doubling of the BCL) after adjustment for age, educational status, current smoking, body mass index, diabetes, and season. However, there was no significant difference in 25(OH)D across the BCL tertiles for men.Conclusions:BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries. An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment. Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships, and to elucidate the exact mechanisms involved.

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简介：AbstractBackground:Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Pressure reactivity index (PRx) have been confirmed to reflect the level of cerebral autoregulation and used to derive optimal cerebral perfusion pressure (CPPopt). The goal of this study is to explore the associations between autoregulation, CPPopt, PRx, and DCI.Methods:Continuous intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP) signals acquired from 61 aSAH patients were retrospectively analyzed. PRx was calculated and collected by Pneumatic computer system. The CPP at the lowest PRx was determined as the CPPopt. The duration of a hypoperfusion event (dHP) was defined as the cumulative time that the PRx was > 0.3 and the CPP was <CPPopt. The duration of CPP more than 10 mmHg below CPPopt (ΔCPPopt < -10 mmHg) was also used to assess hypoperfusion. The percent of the time of hypoperfusion by dHP and ΔCPPopt < -10 mmHg (%dHP and %ΔCPPopt) were compared between DCI group and control group, utilizing univariate and multivariable logistic regression. It was the clinical prognosis at 3 months after hemorrhage that was assessed with the modified Rankin Scale, and logistic regression and ROC analysis were used for predictive power for unfavorable outcomes (mRs 3-5).Results:Data from 52 patients were included in the final analysis of 61 patients. The mean %dHP in DCI was 29.23% and 10.66% in control. The mean %ΔCPPopt < -10 mmHg was 22.28%, and 5.90% in control. The %dHP (p < 0.001) and the %ΔCPPopt < -10mmHg (p < 0.001) was significantly longer in the DCI group. In multivariate logistic regression model, %ΔCPPopt <-10 mmHg (p < 0.001) and %dHP (p < 0.001) were independent risk factor for predicting DCI, and %ΔCPPopt <-10 mmHg (p = 0.010) and %dHP (p = 0.026) were independent risk factor for predicting unfavorable outcomes.Conclusions:The increase of duration of hypoperfusion events and duration of CPP below CPPopt over 10 mmHg, evaluated as time of lowered CPP, is highly indicative of DCI and unfavorable outcomes.

简介：AbstractBackground:Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients.Methods:A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg-1·day-1) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o’clock, 11 to 13 o’clock, and 17 to 19 o’clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups.Results:There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3-10.3] vs. 10.7 [9.1-12.1] mmol/L, Z = -2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1-63.7]% vs. 11.8 [3.0-36.7]%, Z = -2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050).Conclusions:In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients.

简介：AbstractThe aim of this study was to evaluate the performance of an assay using dried plasma spot (DPS) and dried blood spot (DBS) samples for the serological detection of anti-hepatitis C virus (HCV) antibodies. Between January and July 2019, plasma, DPS and DBS specimens were collected from individuals at high-risk for HCV infection. Samples were tested for anti-HCV by ELISA, and the performance of DPS and DBS specimens was examined using results from the plasma testing, as the standard. Blood samples were collected from 329 persons, including 129 men who have sex with men and 200 intravenous drug users. Results from the plasma testing indicated that 118 samples (59.0%) were HCV positive. Data from the DPS sample testing showed sensitivity as 99.2% (95% confidence interval [CI]: 0.95-1.00) and specificity as 100% (95% CI: 0.98-1.00) for HCV detection, with Kappa of 99.3% (95% CI: 0.98-1.00) while in DBS sample testing the sensitivity as 98.3% (95% CI: 0.93-1.00) and specificity as 100% (95% CI: 0.98-1.00), with Kappa of 98.7% (95% CI: 0.97-1.00), respectively. Spearman’s correlation coefficients for the comparisons between plasma and DPS specimen, plasma and DBS specimens, DPS and DBS specimens were 0.857, 0.750, and 0.739, respectively. Compared with the results in plasma, 1 sample was not detected using the DPS specimens, and 2 samples were failed for the positive detection, using the DBS specimens. Both DPS and DBS samples were promising alternatives to plasma, for the detection of anti-HCV antibodies.

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简介：AbstractBackground:Real-time polymerase chain reaction (PCR) is a sensitive and specific method for diagnosing schistosomiasis. However, this method should be performed in a laboratory, usually located distant from the sample collection site. Therefore, it is important to have fast sampling preservation methods, which allow simple transport prior to DNA extraction and amplification. The aim of this study was to verify if blood samples applied to filter paper are suitable for analysis of Schistosoma mansoni DNA by real-time PCR.Methods:A cross-sectional study was conducted among 100 study participants aged 17 to 70 years in a fishing village on the southern shore of Lake Victoria, Tanzania. Serum samples and ethylenediaminetetraacetic acid (EDTA)-anticoagulated whole blood for preparation of dried blood spots (DBS) were collected to test for Schistosoma mansoni infection by real-time PCR. A combined diagnostic reference of positive results of serum-based real-time PCR and the Kato-Katz (KK) method was used for analysis. Sensitivity and negative predictive value (NPV) were calculated. The Wilcoxon signed-rank test was chosen to compare the mean cycle threshold (Ct) values from serum and DBS.Results:According to the reference, 92.5% S. mansoni positive samples were determined. The serum-based real-time PCR performed excellently with 95.4% sensitivity, whereas the DBS-based real-time PCR showed a low sensitivity (45.4%). The Ct-values were significantly higher in DBS (median: 37.3) than in serum samples (median: 27.5, P < 0.001), reflecting a lower parasite-specific DNA load on the filter cards. With increasing egg counts, an increase in sensitivity was observed for all methods. The POC-CCA test and the serum-based real-time PCR showed a sensitivity of 100% for medium and severe infections. The DBS real-time PCR showed a sensitivity of only 85.7% even for severe infections.Conclusions:DBS-based real-time PCR did not provide good results in our study and therefore should not be recommended or must be tested concerning temperature of storage, storage duration, use of different filter papers and extraction methods before it is used in future studies. In contrast, our results showed that the POC-CCA test is a sensitive and precise test for detecting S. mansoni infections.

简介：AbstractBackground:Conventional pressure support ventilation (PSP) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PSN) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PSN and PSP in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.Methods:Eight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.Results:Total AI of PSN was consistently lower than that of PSP in COPD (3% vs. 93%, P = 0.012 for 100% support level; 8% vs. 104%, P = 0.012 for 150% support level), ARDS (8% vs. 29%, P = 0.012 for 100% support level; 16% vs. 41%, P = 0.017 for 150% support level), and post-operative patients (21% vs. 35%, P = 0.012 for 100% support level; 15% vs. 50%, P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PSP but not during PSN in patients with COPD or ARDS. Patients’ inspiratory efforts for triggering and total inspiration were significantly lower during PSN than during PSP in patients with COPD or ARDS under both support levels (P < 0.05). There was no difference in breathing patterns between PSN and PSP.Conclusions:PSN improves patient-ventilator synchrony and generates a respiratory pattern similar to PSP independently of any level of support in patients with different respiratory system mechanical properties. PSN, which reduces the trigger and total patient’s inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PSP.Trial Registration:ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/record/NCT01979627.

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