Effects of the fixed combination of manidipine plus delapril in the treatment of hypertension inadequately controlled by monotherapy with either component: a phase III, multicenter, open-label, clinical trial

Background: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I).Objective: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs]).Methods: In this Phase III, multicenter, open-label, clinical trial, patients with mild to moderate hypertension were assigned to 1 of 2 groups. Group 1 comprised patients whose diastolic BP (DBP) was >90 mm Hg or who experienced AEs with manidipine 20 mg once daily. Group 2 comprised patients who had a DBP >90 mm Hg or who experienced AEs with delapril 30 mg BID. In both groups, patients aged <65 years were to be treated with a fixed combination of manidipine 10 mg plus delapril 30 mg once daily for 12 weeks, whereas patients aged ≥65 years were to be treated with manidipine 5 mg plus delapril 15 mg once daily for 2 weeks and then manidipine 10 mg plus delapril 30 mg once daily for 10 weeks. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks of treatment. At each visit, systolic blood pressure (SBP), DBP, and heart rate were measured 24 hours after dosing, and AEs were recorded.Results: Group 1 included 154 patients (80 men, 74 women; mean [SD] age, 55 [6] years); group 2 included 158 patients (79 men, 79 women; mean [SD] age, 56 [5] years). Mean BP decreased significantly in both groups (P<0.01). Compared with baseline values, mean SBP/DBP decreased 16.2 (3.8)/10.1 (1.9) mm Hg in group 1 and 15.8 (3.1)/11.0 (1.5) mm Hg in group 2 at the last visit. The success rate—rate of normalized DBP (≤90 mm Hg) and responder rate (DBP reduction ≥10 mm Hg)—was 79% in group 1 and 82% in group 2. The rates of treatment-related AEs were 11% in group 1 and 8% in group 2. In group 1, heart rate significantly increased from baseline only at 2 weeks (P<0.05); in group 2, at each visit (P<0.05) except at week 12. However, none of these differences were clinically significant.Conclusion: In this study population of patients whose BP was not adequately controlled by monotherapy, the fixed combination of manidipine 10 mg plus delapril 30 mg, once daily, was effective and well tolerated.     

Evaluation of the effectiveness and tolerability of controlled-release diclofenac-potassium versus immediate-release diclofenac-potassium in the treatment of knee osteoarthritis

Abstract

Background

A controlled-release (CR) form of diclofenac-potassium has been developed, which delivers 100 mg over the course of 24 hours. This formulation is administered QD and provides steady plasmatic levels of the drug.

Objective

The aim of this study was to compare the effectiveness and tolerability of CR diclofenac-potassium versus the immediate-release (IR) formulation, when used for treatment of pain in patients with knee osteoarthritis.

Methods

This prospective, randomized, double-blind, comparative, multi-center, parallel-group study was conducted in male and female patients who had been previously diagnosed with knee osteoarthritis. Inclusion criteria included knee joint pain and ≥3 of the following: age >50 years, morning rigidity lasting <30 minutes, crackling in the joint, pain with applied pressure to the bones, bone hypertrophy, absence of articular heat, and a radiology status of I to III on the Kellgren-Lawrence scale. Patients were randomly divided into 1 of 2 equal-sized groups: 1 group received diclofenac-potassium IR 50 mg BID for 30 days and 1 group received diclofenac-potassium CR 100 mg QD for 30 days. Patients were assessed at baseline and again at 15 and 30 days after initiation of treatment with a physical examination, pain measurement via 100-mm visual analog scale (VAS), and Western Ontario McMaster (WOMAC) osteoarthritis index questionnaire. Adverse events (AEs) were assessed by direct interrogation, hematology controls, blood chemistry, hepatic tests, coagulation tests, and urine tests performed on patients before treatment initiation and on day 30.

Results

Sixty-five patients were screened and 62 patients (mean [SD]age, 61.8 [8.9] years; mean [SD] weight, 71.3 [12.4] kg; female sex, 55 [88.9%]) were included in the study; each study group had 31 patients. After 30 days, both products were equally effective in relieving pain, as measured by VAS (IR, 17.3 vs CR, 21.6; P = NS), and changes in the WOMAC score (IR, 14.5 vs CR, 19.2; P = NS). Significantly more patients in the IR group reported feeling better after 30 days than in the CR group (94% vs 76%; P = 0.002) and, according to the physician''s opinion, significantly more patients treated with diclofenac-potassium IR felt better (97% vs 83%; P = 0.03). Significantly more patients in the IR group required rescue medication than those in the CR group (36% vs 26%; P = 0.03). In the CR group, 7 patients experienced AEs: 6 were gastrointestinal (ie, pyrosis, epigastralgia, dyspepsia) and 1 patient experienced increased arterial pressure. One patient from this group discontinued treatment due to a lack of efficacy. In the IR group, 6 patients experienced AEs (ie, tachycardia, epigastralgia, and pyrosis). One patient discontinued because of AEs, and 3 withdrew due to a lack of efficacy.

Conclusion

Based on the results from this small study in a Venezuelan population, both IR and CR formulations of diclofenac-potassium have similar effectiveness and tolerability profiles.Key Words: diclofenac-potassium, immediate release, controlled release, osteoarthritis     

An open-label comparison of the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) level in an Indian population with dyslipidemia

Abstract

Background:

Patients with dyslipidemia often require the use of >1 lipid-altering agent to achieve the target levels recommended by the National Cholesterol Education Program Adult Treatment Panel III.

Objective:

The aim of this study was to compare the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian population with dyslipidemia.

Methods:

This 12-week, open-label, nonrandomized study was conducted at the Departments of Pharmacology and Medicine, Government Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups. Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks. Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6 and 12 weeks of treatment. Percentage changes from baseline were calculated. Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous reporting.

Results:

Ninety patients were enrolled (50 men, 40 women; 30 patients per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were 18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P < 0.05), but no significant change was seen in group 1. TC levels decreased by a mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs in patients receiving niacin.

Conclusions:

In this study in Indian patients with dyslipidemia, simvastatin-niacin combination therapy was associated with greater changes in lipid profile compared with either agent used alone. Niacin was also associated with greater changes in Lp(a) levels. AEs were less prevalent with combination therapy than with niacin alone.Key words: dyslipidemia, simvastatin, niacin, combination therapy     

A randomized, double-blind, placebo-controlled study of the efficacy and tolerability of policosanol in adolescents with type II hypercholesterolemia

Background: Atherosclerosis begins in childhood and is influenced by risk factors for coronary heart disease (CHD), of which hypercholesterolemia is crucial. The rationale for treating hypercholesterolemia in childhood is to limit atherosclerosis development, for which adherence to a cholesterol-lowering diet is the first-choice therapy. Nevertheless, pharmacological intervention with bile acid-binding resins may be prescribed for patients older than 10 years, mainly those with family history of CHD, multiple risk factors, and/or severe hypercholesterolemia. Resins are effective and tolerable in this population, but their clinical use has been limited because of poor compliance due to unpalatability; other effective cholesterol-lowering drugs have not been recommended in this population because of the potential impact of drug-related adverse effects such as increases in transaminases, myopathies, and gastrointestinal disturbances. Thus, the need for safer, easy-to-take, and effective cholesterol-lowering agents for this population continues. Policosanol is a mixture of higher primary aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects proven in patients with type II hypercholesterolemia and dyslipidemia due to type 2 diabetes mellitus. Policosanol shows good safety and tolerability profiles, with no evidence of drug-related adverse events (AEs) to date. This background supports the idea that policosanol could be a good candidate for treating hypercholesterolemia in children and adolescents, but it requires clinical demonstration.Objective: This 12-week study was undertaken to investigate the cholesterol-lowering effects and tolerability of policosanol in hypercholesterolemic patients aged 11 to 19 years.Methods: In this randomized, double-blind, placebo-controlled study, after 4 weeks of dietary stabilization, adolescents with type II hypercholesterolemia were randomly assigned (1:1 ratio) to receive placebo or policosanol 5-mg tablets once daily for 12 weeks. Physical examinations were performed, and lipid profiles and blood samples were obtained at baseline and after 6 and 12 weeks of therapy. The treatment was considered effective if mean reductions of low-density lipoprotein cholesterol (LDL-C) were >15%. In addition, the percentages of patients reaching final values of LDL-C <3.4 mmol/L and optimal values of <2.8 mmol/L were also evaluated. The doses were doubled if LDL-C values were ≥3.4 mmol/L after 6 weeks of therapy. The incidence of AEs and compliance with study medications were also evaluated after 6 and 12 weeks of treatment.Results: Fifty-five patients were enrolled in the study (28 policosanol, 27 placebo). Twenty-three patients (17 placebo, 6 policosanol) required dose titration at 6 weeks. After 12 weeks of therapy, policosanol significantly decreased LDL-C with respect to baseline and placebo (both P < 0.001), showing a mean reduction of 32.6%. Total cholesterol (TC) and TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were reduced by 21.9%, 27.8%, and 37.2%, respectively, in the policosanol group (P < 0.001, compared with baseline and placebo). HDL-C rose 10.1% (P < 0.001), compared with baseline and placebo. Triglycerides were unaffected by policosanol. LDL-C, TC, and both atherogenic ratios were reduced significantly in the policosanol group (P < 0.001), and significant increases in HDL-C values were observed at the 6-week interim checkup (P < 0.001 vs baseline, P < 0.01 vs placebo). Twenty-five (89.3%) of 28 patients in the policosanol group showed LDL-C reductions >15% compared with 2 (7.4%) of 27 patients in the placebo group (P < 0.001). In addition, 26 (92.8%) of 28 policosanol patients reached LDL-C values < 3.4 mmol/L compared with 4 (14.8%) of 27 patients in the placebo group (P < 0.001). Likewise, the response rate for achievement of optimal values (LDL-C < 2.8 mmol/L) was also larger in the policosanol group (20/28; 71.4%) than in the placebo group (0/27; 0.0%) (P < 0.001). Policosanol was well tolerated, with no drug-related effects found on physical examination. Blood biochemistry determinations revealed significantly lower alanine aminotransferase levels in the policosanol group after 6 weeks of therapy compared with placebo (P < 0.05), as well as significant reductions in aspartate aminotransferase levels at 6 weeks (P < 0.01) and 12 weeks (P < 0.05) compared with baseline. No patients withdrew from the study, and only 3 patients (2 placebo, 1 policosanol) experienced mild AEs during the study; the placebo patients reported abdominal pain and constipation (1 each), and the policosanol patient reported polyphagia.Conclusions: Policosanol 5 mg/d appears to be well tolerated and effective as short-term treatment of hypercholesterolemia in adolescents.     

Effect of alprostadil in the treatment of intensive care unit patients with acute renal injury

BACKGROUNDAcute kidney injury (AKI) is a sudden or rapid decline in the filtration function of the kidneys which is marked by increased serum creatinine or blood urea nitrogen.AIMTo examine the value of alprostadil-assisted continuous venous-venous hemofiltration (CVVH) in the treatment of severe AKI in severely ill patients.METHODSThis was a retrospective study and the inclusion criteria were as follows: (1) Age of patients (≥ 18 years); (2) Admission to intensive care unit due to non-renal primary disease, APACHE II score (≥ 18 points); (3) The diagnostic criteria of AKI guidelines were formulated with reference to the Global Organization for the Improvement of Prognosis in Kidney Diseases, with AKI grades of II-III; (4) All patients were treated with CVVH; and (5) Complete basic data were obtained for all patients.RESULTSThe clinical effect of alprostadil administered in the treatment group was better than that observed in the control group (P < 0.05). The urine output of patients in the alprostadil group returned to normal time (9.1 ± 2.0 d) and was lower than that in the control group (10.6 ± 2.5 d), the difference was statistically significant (P < 0.05); adverse reactions occurred in the alprostadil group compared with the control group, but the difference was not statistically significant (P > 0.05).CONCLUSIONAlprostadil-assisted CVVH in the treatment of severely ill patients with AKI can effectively improve the renal resistance index and partial pressure of urine oxygen, and has a positive effect on improving renal function.     

Efficacy and tolerability of controlled-release paroxetine in the treatment of severe depression: post hoc analysis of pooled data from a subset of subjects in four double-blind clinical trials

OBJECTIVES: The aims of this work were to assess the efficacy and tolerability of controlled-release paroxetine (paroxetine CR) in the treatment of outpatients with severe major depressive disorder (MDD). METHODS: This was a retrospective analysis of pooled data from 4 previously published, double-blind, randomized, placebo-controlled, 8- to 12-week outpatient studies of paroxetine CR (12.5-62.5 mg) in MDD. However, the studies were designed to assess the efficacy of paroxetine CR overall, rather than specifically in those with severe MDD. Subjects were categorized according to their baseline mean 17-item Hamilton Depression Rating Scale (HAMD-17) total score as having severe (> or =25) or nonsevere (<25) depression. Changes in depressive symptomatology were assessed, based on the mean change from baseline in HAMD-17 total scores and the proportion of responders (> or =50% reduction from baseline in HAMD-17 total scores or Clinical Global Impression [CGI] of Improvement scores of 1 or 2), for each study and pooled across the studies. The pooled analysis of data also assessed the proportion of patients achieving remission (HAMD-17 total score < or =7 or CGI-Improvement score of 1) at last-observation-carried-forward end point. RESULTS: A total of 1083 subjects participated in the 4 studies; 303 had severe MDD (paroxetine CR, n = 174; placebo, n = 129). Among the patients with severe MDD, most were women, had a mean HAMD-17 score between 26.3 and 27.7, and had a mean CGI of Severity score between 4.5 and 4.9. In 3 studies, the mean age of such participants was between 35 and 43 years. However, the fourth study was an evaluation in late-life depression in which the mean age was 71.3 years in the paroxetine CR group and 70.0 years in the placebo group. In the overall pooled sample, significantly greater improvements in depressive symptoms were observed among those with severe MDD who were treated with paroxetine CR compared with those who received placebo (HAMD-17 total treatment difference, -4.37 [95% CI, -6.31 to -2.42; P < 0.001]). The odds of CGI-Improvement response were also significantly higher for patients receiving paroxetine CR than those receiving placebo, regardless of baseline depressive symptomatology (severe MDD: odds ratio [OR], 2.42 [95% CI, 1.50-3.91; P < 0.001]; nonsevere MDD: OR, 1.63 [95% CI, 1.21-2.19; P < 0.002] ). Withdrawal rates due to adverse events were 9.8% versus 5.4% (severe) and 5.2% versus 4.5% (nonsevere), paroxetine CR versus placebo, respectively. CONCLUSIONS: This post hoc analysis of pooled data suggests that paroxetine CR was effective and well tolerated in these outpatients with severe MDD.     

Amygdala volume in depressed patients with bipolar disorder assessed using high resolution 3T MRI: The impact of medication

MRI-based reports of both abnormally increased and decreased amygdala volume in bipolar disorder (BD) have surfaced in the literature. Two major methodological weaknesses characterizing extant studies are treatment with medication and inaccurate segmentation of the amygdala due to limitations in spatial and tissue contrast resolution. Here, we acquired high-resolution images (voxel size = 0.55 × 0.55 × 0.60 mm) using a GE 3T MRI scanner, and a pulse sequence optimized for tissue contrast resolution. The amygdala was manually segmented by one rater blind to diagnosis, using coronal images. Eighteen unmedicated (mean medication-free period 11 ± 10 months) BD subjects were age and gender matched with 18 healthy controls, and 17 medicated (lithium or divalproex) subjects were matched to 17 different controls. The unmedicated BD patients displayed smaller left and right amygdala volumes than their matched control group (p < 0.01). Conversely, the BD subjects undergoing medication treatment showed a trend towards greater amygdala volumes than their matched HC sample (p = 0.051). Right and left amygdala volumes were larger (p < 0.05) or trended larger, respectively, in the medicated BD sample compared with the unmedicated BD sample. The two control groups did not differ from each other in either left or right amygdala volume. BD patients treated with lithium have displayed increased gray matter volume of the cortex and hippocampus relative to untreated BD subjects in previous studies. Here we extend these results to the amygdala. We raise the possibility that neuroplastic changes in the amygdala associated with BD are moderated by some mood stabilizing medications.     

Clinical experience with nonstandard doses ofinterferon alfa-2b and ribavirin in the treatment of chronic hepatitis C infection: A retrospective analysis

Background:

Hepatitis C virus (HCV) infection is the most common blood-borne virus in the United States. Several mono- and combination therapies have been approved by the US Food and Drug Administration for the treatment of HCV, but their routes of administration, dosing approaches, eras of introduction, and actual use in clinical practice and resulting effectiveness have not yet been reported.

Objectives:

The aim of this article was to characterize clinical use and virologic response (VR) of the HCV treatments interferon alfa-2b plus ribavirin (IFN + RBV) and peginterferon alfa-2b plus ribavirin (peg-IFN + RBV).

Methods:

This retrospective chart review of office-based practices in theUnited States was conducted at 200 physicians' offices across the United States. We collected data concerning dosing patterns, VR (HCV RNA load, ≤1000 IU/mL or “negative” on polymerase chain reaction qualitative analysis), and adverse events (AEs) from the medical records of a geographically diverse sample of patients receiving treatment for chronic HCV infection in the United States from July 2001 to June 2002. For efficacy assessment, factors that were statistically different at baseline were adjusted using logistic regression. Providers also reviewed the medical records for symptoms or signs consistent with HCV treatment-related AEs.

Results:

Data from the records of 675 patients (423 men, 252 women; mean [SD] age of 45.5 [8.2] years; mean [SD] body weight, 80.8 [19.4] kg) were analyzed. At baseline, the IFN + RBV treatment group (330 patients) had significantly higher percentages of black patients (22.1% vs 15.7%; P = 0.032) and patients with hepatic disease based on clinician-reported cirrhosis and liver dysfunction (18.8% vs 9.9%; P < 0.001), and a significantly lower percentage of white patients (60.3% vs 69.6%; P = 0.012) compared with the peg-IFN + RBV treatment group (345 patients). The difference in log-transformed baseline HCV RNA loads between the 2 treatment groups in this study was <1 log unit. A significantly higher percentage of IFN + RBV-treated patients compared with peg-IFN + RBV-treated patients were prescribed HCV therapy on diagnosis (37.3% vs 29.9%; P = 0.041), and the mean (SD) duration of treatment was significantly different between the 2 treatment groups (52.5 [37.0] vs 27.5 [15.0] weeks; P < 0.001). Peg-IFN + RBV was associated with a higher rate of VR compared with IFN + RBV on univariate analysis (28.5% vs 17.5%; P = 0.018). Recommended doses of peg-IFN and higher-than-recommended doses of RBV were associated with an increased likelihood of VR. Higher-than-recommended doses of peg-IFN without a concomitant increase in RBV was not associated with an increased likelihood of VR. The incidences of the 3 most commonly reported AEs in the IFN + RSV group were significantly higher compared with those in the peg-IFN + RSV group: fatigue, 217 (65.8%) versus 185 (53.6%) patients (P = 0.001); depression, 147 (44.5%) versus 120 (34.8%) (P = 0.009); and anxiety, 87 (26.4%) versus 64 (18.6%) (P = 0.014). Nausea, however, was reported in a significantly higher number of patients in the peg-IFN group compared with the IFN + RBV group (74 [21.4%] vs 51 [15.5%]; P = 0.045). The frequencies of dose modification and treatment discontinuation due to AEs were similar between the 2 treatments and were similar to or less than those reported in other studies.

Conclusions:

In this retrospective data analysis of US office-based practicesconcerning HCV treatment, clinicians were observed to prescribe IFN + RBV at doses that differ from recommendations in the product information (PI), as well as prescribe the RBV component of peg-IFN + RBV at doses that differed from PI recommendations. Although patients treated with peg-IFN + RBV appeared to achieve higher VR compared with those treated with IFN + RBV in our analysis of data from clinical practice, peg-IFN + RBV was associated with lower VR rates compared with those reported in clinical studies.     

Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study

Abstract

Background:

Incadronate has been found to lessen the increase in corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a Phase III study in Japan. The drug is currently used to treat MAH in Japan.

Objective:

The purpose of this study was to assess the clinical usefulness of incadronate in patients with MAH.

Methods:

This open-label study was conducted at 3 medical institutions in Korea. Korean patients with MAH (corrected serum calcium levels ≥11.0 mg/dL) were given a single 10-mg IV infusion of incadronate over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels were determined and subjective symptoms and objective findings (ie, bone pain, spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite, nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of consciousness) were used to monitor the effectiveness of the drug for 6 days after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3 = severe). Adverse events (AEs) were identified by patients'' reports, and adverse drug events (ADEs) were assessed by the investigators throughout the study.

Results:

Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5 years) were included in the study; data from 22 and 24 patients were used to assess effectiveness and tolerability, respectively. Corrected serum calcium level was significantly decreased on day 6 after treatment compared with pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P < 0.001). The antihypercalcemic effect of incadronate became apparent as an inhibition of bone absorption a few days after infusion. Corrected serum calcium level was significantly decreased on days 2 to 6 (P < 0.001) after treatment compared with pretreatment at baseline. Evaluation of symptoms showed significant improvement in the incadronate-treated group (mean total score [range] at baseline, 8 [1–23] and day 6, 5.5 [1–17]; P = 0.001). Eight (33.3%) of the patients were found to have ADEs. Some of the 8 patients experienced >1 ADE (mild and transient fever [13 events], chills [3], headache [1], and myalgia [1]). AEs were observed in 19 (79.2%) of 24 patients. The most frequently reported AE was fever (14 events).

Conclusion:

In this small, open-label study, Korean subjects with MAH treated with incadronate experienced significant improvement in symptoms and calcium levels from baseline.Key Words: incadronate, bisphosphonate, malignancy-associated hypercalcemia, Korea     

Effects of the Cellcultured Acanthopanax senticosus Extract on Antioxidative Defense System and Membrane Fluidity in the Liver of Type 2 Diabetes Mouse

This study examined the effect of cellcultured Acanthopanax senticosus (A. senticosus) extract on the antioxidative defense system, oxidative stress and cell membrane fluidity in the liver of type 2 diabetes in the C57BL/6J mouse as an animal which is genetically prone to develop insulin resistance and obesity/diabetes. C57BL/6J mice were randomly divided, control diet (N-C), high fat diet (DM-C), control diet plus A. senticosus extract (N-CASM), and high fat diet plus A. senticosus extract (DM-CASM). The mice were orally administered an A. senticosus extract (0.5 g/kg body weight) in the N-CASM and DM-CASM groups once a day for 12 weeks, and distilled water in the N-C and DM-C groups. Cellcultured A. senticosus extract was found to be excellent for strengthening the antioxidative defense system, reducing the generation of reactive oxygen species (ROS) and damaging oxidative substances, and maintaing membrane fluidity (MF) in the liver of type 2 diabetes mouse.     

Comparison of methimazole/hydrocortisone ointment with oral methimazole in patients with graves disease: A prospective, randomized, open-label, parallel-group, 18-month study

Background: Thionamide antithyroid drugs (ATDs) have certain disadvantages and are associated with some adverse events (AEs). To overcome the problems associated with ATDs, a compound antithyroid ointment (CATO) containing methimazole (MMI) and hydrocortisone has been developed for use as a local thyroid treatment (LTT).Objective: The aim of this study was to assess the clinical effectiveness and tolerability of CATO LTT in patients with Graves disease (GD).Methods: This was a prospective, randomized, open-label, parallel-group clinical trial conducted at the Provincial Hospital Affiliated to Shandong University (Jinan, China). Patients with GD aged 19 to 65 years were randomized to receive either CATO LTT 0.3 g/d or oral MMI 37.5 mg/d (control group) treatment for 18 months, with a 4-year follow-up period. Hyperthyroid symptoms, thyroid function, granulocyte count, liver function, and AEs were assessed at baseline and every 2 weeks until serum thyroid hormone (TH) concentration normalized, at which point patients were assessed monthly. The primary efficacy end points were the duration of treatment required for serum TH concentration to normalize and the remission rate after completing the 18-month treatment regimen.Results: A total of 154 patients (133 women, 21 men; mean [SD] age, 39.6 [11.8] years; all Han Chinese) participated in the study; all patients completed the 18-month treatment period. Compared with the MMI group (n 76), the CATO- treated group (n 78) had a significantly shorter median (range) time to restoration of normal serum thyroid hormone concentration (43 [12-150] vs 22 [7-60] days; P < 0.001), a significantly lower rate of recurrence of hyperthyroidism (309/1520 [20.3%] vs 193/1368 [14.1%] person-time; P < 0.001), a significantly lower drug hypothyroidism rate (185/1520 [12.2%] vs 54/1368 [3.9%] person-time; P < 0.001), and a higher remission rate (year 1:46/69 [66.7%] vs 65/72 [90.3%] patients, P 0.001; year 2:40/69 [58.0%] vs 60/72 [83.3%] patients, P - 0.001; year 3:34/69 [49.3%] vs 57/72 [79.2%] patients, P < 0.001; and year 4:30/69 [43.5%] vs 55/72 [76.4%] patients, P < 0.001). Systemic AEs occurred in 6 patients (7.9%) in the MMI group (drug neutropenia, 2 patients [2.6%]; epistaxis, 1 [1.3%]; hepatopathy, 1 [1.3%]; and other systemic AEs, 2 [2.6%]), while no systemic AEs were observed/reported in the CATO group.Conclusion: This study suggests that CATO LTT was well tolerated and more effective than oral MMI treatment in controlling thyrotoxicosis and promoting remission of GD in these Han Chinese patients.     

Effects of atorvastatin 10 mg and fenofibrate 200 mg on the low-density lipoprotein profile in dyslipidemic patients: A 12-week, multicenter, randomized, open-label, parallel-group study

Background: Elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations are highly atherogenic, especially the small, dense LDL (sdLDL) species. Fenofibrate has been reported to shift the LDL profile by decreasing the sdLDL subfraction and increasing larger LDL subclasses. Atorvastatin, anantihyperlipidemic agent, has been reported to reduce plasma total cholesterol (TC) and triglyceride (TG) concentrations and thus could modify the LDL profile.Objective: The aim of this study was to compare the effects of fenofi brate and atorvastatin on standard lipid concentrations and the LDL profile.Methods: In this randomized, open-label, parallel-group study, men and women aged 18 to 79 years with type II primary dyslipidemia, defined as LDL-C ≥160 and TG 150 to 400 mg/dL, after a 4- to 6-week washout period while eating an appropriate diet, were randomized to receive either atorvastatin 10 mg once daily or fenofi-brate 200 mg once daily. Plasma lipid concentrations and cholesterol and apolipoprotein (apo) B (reflecting the LDL particle number) in each LDL subfraction prepared by ultracentrifiigation were determined at baseline and after 12 weeks of treatment. Tolerability was assessed using adverse events (AEs) obtained on laboratory analysis and vital sign measurement. Adherence was assessed by counting unused drug supplies.Results: A total of 165 patients (117 men, 48 women; mean [SD] age, 50.1 [10.7] years; mean TC concentration, 289 mg/dL) were randomized to receive atorvastatin (n = 81) or fenofibrate (n = 84). Compared with fenofibrate, atorvastatin was associated with a significantly greater mean (SD) percentage decrease in TC (27.0% [12.3%] vs 16.5% [12.9%]; P < 0.001), calculated LDL-C (35.4% [15.8%] vs 17.3% [17.2%]; P < 0.001), TC/high-density lipoprotein cholesterol (HDL-C) ratio (29.1% [16.3%] vs 22.9% [15.9%]; P = 0.001), and apoB (30.3% [12.7%] vs 19.6% [15.5%]; P < 0.001). Compared with atorvastatin, fenofibrate was associated with a significantly greater decrease in TG (37.2% [25.9%] vs 20.2% [27.3%]; P < 0.001) and a significantly greater increase in HDL-C concentration (10.4% [15.7%] vs 4.6% [12.1%]; P = 0.017). Fibrinogen concentration was significantly different between the 2 groups (P = 0.002); it was decreased with fenofibrate use (4.6% [23.7%]) and was increased with atorvastatin use (5.7% [23.5%]). Atorvastatin did not markedly affect the LDL distribution; it was associated with a homogeneous decrease in cholesterol and apoB concentrations in all subfractions, whereas fenofibrate was associated with a marked movement toward a normalized LDL profile, shifting the sdLDL subfractions toward larger and less atherogenic particles, particularly in those patients with baseline TG ≥200 mg/dL. No serious AEs related to the study treatments were reported. A total of 5 AEs were observed in 8 patients, including: abdominal pain, 3 patients (2 in the atorvastatin group and 1 in the fenofibrate group); abnormal liver function test results, 1 (fenofibrate); increased creatine Phosphokinase activity, 2 (atorvastatin); gastrointestinal disorders, 1 (fenofibrate); and vertigo, 1 (fenofibrate).Conclusion: In these dyslipidemic patients, fenofibrate treatment was associated with an improved LDL subfraction profile beyond reduction in LDL-C, particularly in patients with elevated TG concentration, whereas atorvastatin was associated with equally reduced concentrations of cholesterol and apoB in all LDL subfractions independent of TG concentrations.     

Value of GRACE and SYNTAX scores for predicting the prognosis of patients with non-ST elevation acute coronary syndrome

BACKGROUNDGRACE and SYNTAX scores are important tools to assess prognosis in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, there have been few studies on their value in patients receiving different types of therapies.AIMTo explore the value of GRACE and SYNTAX scores in predicting the prognosis of patients with NSTE-ACS receiving different types of therapies. METHODSThe data of 386 patients with NSTE-ACS were retrospectively analyzed and categorized into different groups. A total of 195 patients who received agents alone comprised the medication group, 156 who received medical therapy combined with stents comprised the stent group, and 35 patients who were given agents and underwent coronary artery bypass grafting (CABG) comprised the CABG group. General information was compared among the three groups. GRACE and SYNTAX scores were calculated. The association between the relationship between GRACE and SYNTAX scores and the occurrence of major adverse cardiovascular events (MACEs) was analyzed. Pearson’s correlation analysis was used to determine the factors influencing prognosis in patients with NSTE-ACS. Univariate and multivariate analyses were conducted to analyze the predictive value of GRACE and SYNTAX scores for predicting prognosis in patients with NSTE-ACS using the Cox proportional-hazards model. RESULTSThe incidence of MACE increased with the elevation of GRACE and SYNTAX scores (all P < 0.05). The incidence of MACE was 18.5%, 36.5%, and 42.9% in the medication group, stent group, and CABG group, respectively. By comparison, the incidence of MACE was significantly lower in the medication group than in the stent and CABG groups (all P < 0.05). The incidence of MACE was 6.2%, 28.0% and 40.0% in patients with a low GRACE score in the medication group, stent group, and CABG group, respectively (P < 0.05). The incidence of MACE was 31.0%, 30.3% and 42.9% in patients with a medium GRACE score in the medication group, stent group, and CABG group, respectively (P > 0.05). The incidence of MACE was 16.9%, 46.2%, and 43.8% in patients with a high GRACE score in the medication group, stent group, and CABG group, respectively (P < 0.05). The incidence of MACE was 16.2%, 35.4% and 60.0% in patients with a low SYNTAX score in the medication group, stent group, and CABG group, respectively (P < 0.05). The incidence of MACE was 37.5%, 40.9%, and 41.7% in patients with a medium SYNTAX score in the medication group, stent group, and CABG group, respectively (P > 0.05). MACE incidence was 50.0%, 75.0%, and 25.0% in patients with a high SYNTAX score in the medication group, stent group, and CABG group, respectively (P < 0.05). Univariate Cox regression analyses showed that both GRACE score (hazard ratio [HR] = 1.212, 95% confidence interval [CI]: 1.083 to 1.176; P < 0.05) and SYNTAX score (HR = 1.160, 95%CI: 1.104 to 1.192; P < 0.05) were factors influencing MACE (all P < 0.05). Multivariate Cox regression analyses showed that GRACE (HR = 1.091, 95%CI: 1.015 to 1.037; P < 0.05) and SYNTAX scores (HR = 1.031, 95%CI: 1.076 to 1.143; P < 0.05) were independent predictors of MACE (all P < 0.05). CONCLUSIONGRACE and SYNTAX scores are of great value for evaluating the prognosis of NSTE-ACS patients, and prevention and early intervention strategies should be used in clinical practice targeting different risk scores.     

Can acupuncture combined with SSRIs improve clinical symptoms and quality of life in patients with depression? Secondary outcomes of a pragmatic randomized controlled trial

ObjectivesTo explore the effects of acupuncture (manual acupuncture or electroacupuncture) combined with SSRIs for moderate to severe depression improving major clinical symptoms and life quality of the patients on secondary outcomes.DesignPragmatic, parallel, randomized controlled trial.Setting6 hospitals in China.Interventions6 weeks of manual acupuncture (MA)+selective serotonin reuptake inhibitors (SSRIs), electroacupuncture (EA)+SSRIs, and SSRIs alone.Main outcome measuresThe primary outcome was response rate of 17-item Hamilton Depression Scale (HAMD-17) total score at 6^th week. The secondary outcomes reported in this analysis were HAMD-17 factor scores at 1^st, 2^nd, 4^th, 6^th, 10^th week and WHO Quality of Life-BREF (WHOQOL-BREF) scores at 6^th week.Results477 patients were randomly assigned into MA + SSRIs (n = 161), EA + SSRIs (n = 160), or SSRIs alone (n = 156) groups. For HAMD-17 (at 6^th week), the MA + SSRIs group was significantly better than the SSRIs alone group in retardation factor (p = 0.008), while the EA+SSRIs group was significantly better than the SSRIs alone group in anxiety/somatization factor (p<0.001) and sleep disturbance factor (p = 0.002). For WHOQOL-BREF (at 6^th week), the EA + SSRIs group, compared with the SSRIs alone group, produced a more significant improvement in the overall quality of life, general health, physical health, and psychological health (p<0.05). While, the MA + SSRIs group, compared to the SSRIs alone group, showed significant advantage only in psychological health (p = 0.023).ConclusionsEither MA or EA combined SSRIs treatment could improve symptoms and quality of life for patients with moderate to severe depression. The main limitation of this trial was not using a sham control therefore the placebo effect could not be excluded.     

A pilot controlled trial of a combination of electroacupuncture and psychological intervention for post-stroke depression

ObjectiveThis study was to investigate effects of a combination of electroacupuncture (EA) and psychological intervention (PI) for post-stroke depression (PSD) and provide treatment suggestionsMethodsIn a single-blind, randomized controlled trial, 49 patients with PSD were randomly divided into two groups, PI group (n = 23) and PI+EA group (n = 26). PI group received PI 2 times a week by a professional psychologist. In addition to PI treatment, PI+EA group was treated with EA at GB13 and HT7, 30 min, 5 times a week, 4 weeks as a course of treatment, a total of 12 weeks. The 17-item Hamilton Rating Scale for Depression (HAMD-17) and Lo Knapp Ron J's sleep score table were measured before treatment, 4 weeks, 8 weeks and 12 weeks after treatment.ResultsAfter 12 weeks of PI or PI+EA therapy, 42 of 49 patients were effective and 7 were ineffective, with an effective rate of 85.7 %. Among them, the effective rate of PI group alone was 78.3 %, and the effective rate of PI+EA group was 92.3 %. Compared with values of PI, HAMD-17 values at 8 weeks of PI+EA treatment were significantly decreased (P < 0.01). At the same time, Sleep Score table was significantly decreased after PI+EA treatment (P < 0.05). Incidence of adverse events was not different in the two groupsConclusionA combination of EA and PI maybe an effective and safe treatment option for PSD, which is statistically more significant than PI treatment alone. Due to small samples involved in this pilot study, further research is needed to see whether a combination of EA and PI will match the results of this pilot study.     

The safety of tai chi: A meta-analysis of adverse events in randomized controlled trials

ObjectivesTo review current publications to examine safety of tai chi (TC).DesignCochrane Library, EBSCO host and MEDLINE/PubMed were searched for randomized controlled trials (RCTs) including TC as the core intervention and reporting adverse events (AEs). Data were extracted considering active vs. inactive control group comparisons and presence of an AE monitoring protocol. Meta-analyses were conducted for overall results as well as control group and reporting specific conditions.ResultsIn 256 RCTs of TC, 24 met eligibility criteria (1794 participants) and were assessed using the Cochrane Risk of Bias tool. The frequency of non-serious, serious and intervention-related AEs were not found to be significantly different between TC and inactive or active control conditions. In studies with an AE monitoring protocol, more non-serious adverse events (RD = 0.05; 95% CI: 0.00, 0.10; P = 0.05) were reported for TC compared to inactive interventions. Given the higher overall AE risks related to studies of participants with heart failure, additional analyses examined this set separately. More serious AEs were found for inactive interventions compared with TC in studies with heart failure participants (RD = −0.11; 95% CI: −0.20, −0.03; P = 0.01).ConclusionFindings indicate that TC does not result in more AEs than active and inactive control conditions, and produces fewer AEs than inactive control conditions for heart failure patients.     

抑郁症及抑郁高血压共病患者脑部基于体素的磁共振扩散峰度成像研究

目的 探讨磁共振扩散峰度成像(DKI)在评价抑郁症及抑郁高血压共病患者脑部微观结构损害中的应用价值。方法 收集20例抑郁症患者(抑郁症组)、26例抑郁高血压共病患者(共病组)、26例高血压患者(高血压组)、23名健康志愿者(正常对照组),采用3.0T磁共振仪进行DKI扫描,使用DKE软件计算平均扩散峰度(MK)值;比较4组间MK值的差异;比较差异脑区平均MK值与17项汉密尔顿抑郁量表(HAMD-17)评分的相关性。结果 相对于正常对照组,抑郁症组MK值减低的脑区包括右额中回、右梭状回、右前扣带回、左中扣带回、左后扣带回、右岛叶、右海马、右枕下回及左枕中回、双侧楔前叶、双侧壳核、两侧颞下回和颞中回(P<0.05),共病组MK值减低的脑区包括右额上回、右梭状回、右前扣带回、右中扣带回、左后扣带回、双侧海马、双侧海马旁回、左枕中下回、双侧楔前叶、右壳核、左舌回、双侧颞中回及颞下回及左侧丘脑(P<0.05),高血压组无MK减低区。相对于抑郁症组,共病组MK下降脑区为右额下回、右梭状回、右岛叶、右扣带前回(P<0.05)。右侧海马(r=0.421,P<0.001)及右侧额中回(r=0.400,P=0.001)的平均MK值与HAMD-17评分呈负相关。结论 抑郁症和抑郁共病患者存在广泛的额叶-皮层下-边缘系统脑白质微观结构损害和功能异常;高血压可能对抑郁症有协同作用。     

Influence of volar margin of the lunate fossa fragment fixation on distal radius fracture outcomes: A retrospective series

BACKGROUNDDistal radius fractures accompanied by the volar margin of the lunate fossa (VMLF) lesions are often overlooked or inadequately reduced in clinical practice. AIMTo investigate the impact of VMLF fragment in distal radius fractures on the stability and function of the wrist joint.METHODSThis was a retrospective study of patients with distal radius fractures who underwent surgical treatment between January 2013 and December 2017. The patients were divided into two groups according to whether the VMLF fragments were fixed or not. X-rays and computed tomography were performed before surgery, immediately postoperatively, and at 1, 3, and 6 mo to measure the scapholunate angle, radiolunate angle, capitolunate angle, and effective radiolunate flexion (ERLF). The Mayo wrist score and disabilities of the arm, shoulder, and hand (DASH) score were determined at 1 year. RESULTSThirty-five patients were included. There were 15 males and 20 females. Their mean age was 52.5 ± 14.3 (range: 19-70) years. There were 38 wrists (17 on the left side, 15 on the right, and three bilateral; 16 in the fixed group, and 22 in the unfixed group). The interval between trauma and surgery was from 1 h to 1 mo. The incidence of postoperative wrist instability in the unfixed group (86.4%) was higher than in the fixed group (25.0%) (P ≤ 0.001). Ten patients had ERLF > 25° in the unfixed group and none in the fixed group (P = 0.019). The Mayo wrist score was 94 ± 5.7 in the fixed group and 68 ± 15.1 in the unfixed group (P < 0.001). The DASH score was 4.6 ± 2.5 in the fixed group and 28.5 ± 19.5 in the unfixed group (P < 0.001). CONCLUSIONInjuries of VMLF, even small fractures, might damage the radial-lunar ligament, leading to postoperative wrist instability, sagittal force line imbalance, and poor recovery of wrist joint function.