Efficacy of combination therapy of interferon-α with ursodeoxycholic acid in chronic hepatitis C: A randomized controlled clinical trial

The efficacy of interferon- therapy in the treatment of chronic hepatitis C is still limited. A combination therapy of interferon- with ursodeoxycholic acid (UDCA) was tested for its efficacy in the treatment of chronic hepatitis C by a randomized controlled study. Eighty consecutive Japanese patients with chronic hepatitis C were randomly divided into two groups: one group was treated with interferon- (group A,n=40) and the other with a combination of interferon- and UDCA (group B,n=40). In both groups, human interferon- (6 million units per day) was intramuscularly injected daily for 2 weeks and then three times a week for 22 weeks: this 24-week period was followed by 24 weeks of observation. In group B, UDCA was also administered, daily at a dose of 600mg orally, from the beginning of the interferon therapy and administration was continued for 48 weeks. The rates for ALT normalization and clearance of hepatitis C virus (HCV) viremia at the end of the 24-week interferon therapy were similar for groups A and B (58% vs 60% and 55% vs 48%, respectively). At the end of the 24-week follow-up, the sustained normalization rates for ALT levels for the two groups were not different (35% vs 43%), while the rate of clearance was higher in group B (40%) than in group A (23%), but the difference was not significant (P=0.14). The sustained complete response, i.e., HCV RNA negativity at the end of the follow-up, as well as the maintenance of ALT normalization during the follow-up period, was more frequent in group B (38%) than in group A (18%) although the difference was not significantP=0.08). The rate of HCV reactivation after interferon was discontinued was significantly lower in group B (16%) than in group A (59%) (P<0.01). Although this combination therapy did not lead to a sufficiently sustained complete response, it could serve as adjuvant antiviral therapy when a suitable dosage and administration period are determined.     

Wellbeing,resilience, and coping: Are there differences between healthy older adults,adults with mild cognitive impairment,and adults with Alzheimer-type dementia?

The changes that occur with cognitive impairment and Alzheimer’s disease could affect psychological aspects unrelated to memory. The purpose of this study is to compare 32 healthy older adults, 31 amnestic mild cognitively impaired (aMCI) adults, and 32 patients diagnosed with Alzheimer's disease (AD), in order to determine whether there are differences in their psychological wellbeing, resilience, and coping strategies. Unifactorial MANOVAS and ANOVAS were performed to analyze the between-group differences. The results reveal that the AD group showed lower levels of resilience and orientation toward problem-solving and greater use of religious strategies. In addition, they had significantly lower wellbeing scores than the other groups. The worsening of the pathology impedes the capacity for adaptation and resilience and the application of strategies oriented toward the problem, and it increases the application of strategies based on magical thinking. Moreover, it also produces a reduction in wellbeing.     

A randomized controlled clinical trial on the treatment of Thymosin-a1 versus interferon-α in patients with hepatitis B

INTRODUCTIONChronic hepatitis B virus(HBV)infection is aserious problem because of its worldwidedistribution and possible adverse sequelae,such ascirrhosis and hepatocellular carcinoma(HCC).The World Health Organization estimates that HBVhas infected more than 350 million peopleworldwide,and up to 20% of those infected with     

Short-term trial of etanercept in Behçet's disease: a double blind, placebo controlled study

OBJECTIVE: To determine the effect of the tumor necrosis factor-alpha blocker etanercept on the pathergy and monosodium urate (MSU) status and on the mucocutaneous and articular manifestations of patients with Beh?et's disease (BD). METHODS: Forty male patients with BD, all with positive pathergy and MSU tests and mucocutaneous disease and/or arthritis, were randomized (20 patients to each study arm) to receive either etanercept 25 mg twice a week or placebo for 4 weeks. The pathergy and MSU responses and the frequencies of mucocutaneous and articular manifestations were compared between the 2 groups. RESULTS: There were no decreases in the pathergy and MSU responses in the etanercept group compared to the placebo group at any time. The mean numbers of oral ulcers, nodular lesions, and papulopustular lesions were less in the etanercept group compared to the placebo group at all weekly evaluations, except for the second week for papulopustular lesions. The probability of being free of oral ulcers and nodular lesions was also significantly higher in the former group (log-rank chi-square = 9.83, p = 0.0017; log-rank chi-square = 14.17, p = 0.0002, respectively). CONCLUSION: Etanercept did not affect the pathergy reaction and the cutaneous response to MSU crystals. However, the drug was effective in suppressing most of the mucocutaneous manifestations of BD.     

Pre-frail older adults show improved cognition with StayFitLonger computerized home–based training: a randomized controlled trial

GeroScience - Multidomain interventions have shown tremendous potential for improving cognition in older adults. It is unclear if multidomain interventions can be delivered remotely and whether...     

A randomized controlled clinical trial： Interruption of intrauterine transmission of hepatitis B virus infection with HBIG

AIM: To evaluate the efficacy of interruption of intrauterine infection of HBV with HBIG in pregnant women with positive HBeAg and HBsAg. METHODS: A prospective randomized controlled trial was adopted. Sixty cases with positive HBeAg and HBsAg were coincident with the criteria of inclusion, and 8 cases were excluded. Fifty-two cases were analyzed (28 cases in trial group and 24 in control group). All cases in trial group received 200 IU HBIG intravenously every 4 wk for 3 times from the 28th wk. The cases of control group received placebo in the same way. All pregnant women were detected for HBeAg and HBV-DNA at the beginning of the trial and end of the trial (delivery). The cord blood of all newborns were collected for detecting HBeAg and HBV-DNA simultaneously. RESULTS: For investigation of HBeAg of newborns in trial group, 6 of 28 cases of newborns had positive HBeAg, the HBeAg positive rate being 21.4%, the total rate of 95% CI being 8%-41%. In control group, 19 of 24 cases of newborns had positive HBeAg, HBeAg positive rate was 79.2%, the rate of 95%CI being 5%-93%. By statistical analysis, x2 = 17.26, P < 0.01, RR = 0.27, 95% CI (6.3×10-6, 8.6×10-5). For investigation of HBV-DNA of newborns in trial group, 7 of 28 cases of newborns had positive HBV-DNA, HBV-DNA positive rate being 25%, the total rate of 95% CI being ll%-45%. In control group, 20 of 24 cases of newborns had positive HBV-DNA, HBV-DNA positive rate was 83.3%, the total rate of 95% CI being 63%-95%. By statistical analysis, x2 = 17.62, P < 0.01, RR = 0.30, 95% CI (1.5×10-5, 1.7×10-4). The results indicated that there was significant difference in HBeAg positive rate and HBV-DNA positive rate of newborns between the two groups. In trial group, 7 of 28 newborns had HBV-DNA positive, but the HBV-DNA load of newborns was lower than that of their mothers. In control group, 20 of 24 newborns still had HBV-DNA positive, and the HBV-DNA load of newborns was close to those of their mothers. Statistical analysis indicated that there was no significant difference in HBV-DNA load between postnatal women without HBIG intervention and their filial generations (T = 81.5, P > 0.1). CONCLUSION: It is effective and safe to prevent in-trauterine infection of HBV with HBIG from the 28th wk in pregnant women with positive HBeAg and HBsAg. In clinical application, those pregnant women with negative HBeAg and positive HBV-DNA also need to be interrupted by HBIG.     

Activity in older adults: cause or consequence of cognitive functioning? A longitudinal study on everyday activities and cognitive performance in older adults

The impact of three types of everyday activities (i.e., social, experiential, and developmental) on four cognitive functions (i.e., immediate recall, learning, fluid intelligence, and information-processing speed) and one global indicator of cognitive functioning (Mini-Mental State Exam score) over a period of 6 years was studied in a large 55--85 year-old population-based sample (N = 2,076). A cross-lagged regression model with latent variables was applied to each combination of 1 cognitive function and 1 type of activity, resulting in 15 (3 x 5) different models. None of the activities were found to enhance cognitive functioning 6 years later when controlling for age, gender, level of education, and health, as well as for unknown confounding variables. Conversely, one cognitive function (i.e., information-processing speed) appeared to affect developmental activity. It is suggested that no specific activity, but rather socioeconomic status to which activities are closely connected, contributes to maintenance of cognitive functions.     

Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis:A randomized,double blind,placebo-controlled,multicenter clinical study

AIM:To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS:It was a randomized,double blind,placebo- controlled,multicenter clinical study.One hundred and forty- four patients were divided into oxymatrine capsule group (group A)and placebo group(group B).The course was 52 wk.Patients were visited once every 12 wk and the last visit was at 12 wk after cessation of the treatment.All patients had liver biopsy before treatment,part of them had a second biopsy at the end of therapy.Clinical symptoms,liver function test,serum markers of hepatic fibrosis were tested.Ultrasound evaluation was performed before,during and at the end of therapy. RESULTS:One hundred and forty-four patients enrolled in the study.Of them 132 patients completed the study according to the protocol,49 patients had liver biopsy twice(25 patients in group A and 24 in group B).At the end of therapy,significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system(SSS)were achieved in group A.The total effective rate of the treatment was 48.00%,much higher than that of 4.17% in group B (P<0.05).Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid(HA)and type Ⅲ procollagenic peptide(P Ⅲ P)in group A was seen(P<0.05).The total effective rate of serum markers at the end of therapy in group A was 68.19%,much higher than that of 34.85% in group B(P<0.05).The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%,much higher than that of 30.30% in group B(P<0.05).The rate of adverse events was similar in two groups. CONCLUSION:Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.     

Hemodynamic effects of propranolol with spironolactone in patients with variceal bleeds： A randomized controlled trial

AIM： To study the hemodynamic effects of spironolactone with propranolol vs propranolol alone in the secondary prophylaxis of variceal bleeding. METHODS： Thirty-five cirrhotics with variceal bleeding randomly received propranolol （n = 17： Group A） or spironolactone plus propranolol （n = 18： Group B）. Hemodynamic assessment was performed at baseline and on the eighth day. RESULTS： Spironolactone with propranolol caused a greater reduction in the hepatic venous pressure gradient than propranolol alone （26.94% vs 10.2%; P 〈 0.01）. Fourteen out of eighteen patients on the combination treatment had a reduction in hepatic venous pressure gradient to≤ 12 mmHg or a 20% reduction from baseline in contrast to only six out of seventeen （6/17） on propranolol alone （P 〈 0.05）. CONCLUSION： Spironolactone with propranolol results in a better response with a greater reduction in hepatic venous pressure gradient in the secondary prophylaxis of variceal bleeding. A greater number of patients may be protected by this combination therapy than by propranolol alone. Hence, this combination may be recommended for secondary prophylaxis in patients with variceal bleeding.     

Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria – A double blind randomized placebo-controlled crossover trial

AimsSodium glucose transport inhibitors (SGLT2i) can reduce risk of heart failure (HF) and cardiovascular death in people with type 2 diabetes (T2D) and existing cardiovascular disease. Our aim was to examine the effect of the SGLT2i dapagliflozin on cardiac function in people with T2D and albuminuria.MethodsA secondary analysis of a double-blind, randomized, cross-over study of 12 weeks treatment with dapagliflozin 10 mg versus placebo. Myocardial function was assessed by echocardiography and biomarkers of cardiac risk were measured. An exploratory diastolic composite of echocardiographic variables was computed.ResultsOf the 36 participants completing the study 89% were male, mean age 64 ± 8 years, diabetes duration 16.4 ± 4.7 years and HbA_1c 73 ± 15 mmol/mol (8.9 ± 1.4%), 30.6% had former cardiovascular events and 32% had macroalbuminuria. Mean left ventricular ejection fraction (LVEF) was 55.4% after placebo and 54.3% after dapagliflozin (p = 0.15), global longitudinal strain −16.1 vs. −15.9, (p = 0.64), E/e′ 7.6 vs. 7.6 (p = 0.082), and tissue Doppler velocity e′ 10.0 vs. 10.6 (p = 0.05). The composite score showed diastolic function improvement of 19.8% (p = 0.021). No other significant changes were observed.ConclusionsDapagliflozin may have minor effects on diastolic function in people with T2D, albuminuria and preserved LVEF.     

A phase III randomized,multicentre, double blind,active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia – the TEAM-ET 2·0 trial

Anagrelide is an established treatment option for essential thrombocythaemia (ET). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active-controlled, non-inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A-PR) over a reference product in high-risk ET patients, either anagrelide-naïve or -experienced. In a 6 to 12-week titration period the individual dose for the consecutive 4-week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822 × 10⁹/l (95% confidence interval (CI) 707–936 × 10⁹/l) and 797 × 10⁹/l (95% CI 708–883 × 10⁹/l) for A-PR and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281 × 10⁹/l for A-PR (95% CI 254–311) and 305 × 10⁹/l (95% CI 276–337) for the reference product (P < 0·0001, for non-inferiority). Safety and tolerability were comparable between both drugs. The novel prolonged-release formulation was equally effective and well tolerated compared to the reference product. A-PR provides a more convenient dosing schedule and will offer an alternative to licensed immediate-release anagrelide formulations.     

The effect of daily fortified yogurt consumption on weight loss in adults with metabolic syndrome: A 10-week randomized controlled trial

Background and Aims

Obesity is a complex and multifaceted condition. Thus, functional foods need investigation as novel adjunct treatments for obesity. The objective was to determine the effects of daily consumption of a fortified yogurt (FY) on weight loss in overweight and obese patients with metabolic syndrome on a caloric-restricted diet.

Exercise training in older adults,what effects on muscle force control? A systematic review of randomized clinical trials

AimTo determine the magnitude of the effects of different exercise training (ET) modalities on variables of muscle force control in older adults.MethodsRelevant articles were searched in PubMed, Web of Science, Science Direct and Scopus, using the keywords: Aged AND “Exercise Movement Techniques” AND (“Complexity of torque” OR “Complexity of force” OR “Variability of torque” OR “Variability of force” OR “Force Steadiness” OR “Force fluctuations”). To be included in the full analysis, the studies had to be randomized controlled trials in which older adults were submitted to ET programs and muscle force control assessment.ResultsThe searches resulted in 702 articles from which 6 met all the inclusion criteria. The trials involved 171 healthy and functionally limited older adults (71.64 ± 1.53 years). Studies included resistance, steadiness and functional training programs. Training sessions were 2–3 time per week, lasted 6–16 months with intensities determined as percentage of the one repetition maximum loads. There is a heterogeneity regarding experimental set-up and data analysis parameters between studies. The findings show an improved muscle force control in older adults after ET. Such response is better evidenced by the assessment of the coefficient of variation (CV) of the force signals. There is moderate evidence that resistance training programs are effective to decrease CV of knee extensor force signals at lower force targets.ConclusionsThe findings from this review suggest that ET programs are effective to improve muscle force control in older adults.     

Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis： A randomized, double blind, placebo-controlled, multicenter clinical study

AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebocontrolled, multicenter clinical study. One hundred and fortyfour patients were divided into oxymatrine capsule group (group A) and placebo group (group B). The course was 52wk. Patients were visited once every 12wk and the last visit was at 12wk after cessation of the treatment. All patients had liver biopsy before treatment, part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol, 49 patients had liver biopsy twice (25 patients in group A and 24 in group 13). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P&lt;0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type Ⅲ procollagenic peptide (PⅢ P) in group A was seen (P&lt;0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P&lt;0.05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P&lt;0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.     

Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C： A randomized controlled clinical trial

AIM: To study the therapeutic effect of interferon (IFN) and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection. METHODS: A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFN-alpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defined as negative HCV-RNA in the serum 6 mo after treatment. RESULTS: There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P<0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P=0.019). CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.     

Adiponectin,leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment

The aim of the study was to determine the serum levels of adiponectin, leptin and IL-1 β in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine the associations of these markers with clinical and cognitive parameters. A biochemical evaluation was performed of 62 seniors with type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI (controls). Serum leptin and IL-1 β levels were higher and adiponectin concentration was lower in MCI patients than controls. In MCI subjects, adiponectin level was negatively correlated with leptin, IL-1 β levels and BMI. Leptin concentration was correlated with IL-1 β level. Univariate logistic regression models revealed that the factors which increased the likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels of HbA1c, leptin, IL-1 β and triglycerides, as well as lower levels of adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension, hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of diabetes, increased number of co-morbidities, older age, fewer years of formal education were found to be associated with MCI. The multivariable model indicated fewer years of formal education, previous CVD, hypertension, increased number of co-morbidities, higher HbA1c and IL-1 β levels and lower adiponectin level. Elderly diabetic patients with MCI have higher levels of leptin and IL-1 β and lower levels of adiponectin. Further prospective studies are needed to determine the role of these markers in the progression to dementia.     

Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double-blind, randomized, controlled, emergency department trial

STUDY OBJECTIVE: This study was conducted to investigate the frequency and severity of adverse effects, specifically emergence phenomena, experienced by patients receiving intravenous ketamine with or without midazolam for sedation in a pediatric emergency department. METHODS: Patients aged 4.5 months to 16 years receiving ketamine sedation were prospectively enrolled in a double-blind, randomized, controlled study at a university-affiliated children's hospital-pediatric ED. All patients received ketamine (1 mg/kg) and glycopyrrolate (5 microgram/kg) intravenously. Patients were randomly assigned to receive midazolam (0.1 mg/kg) intravenously or no midazolam. Total time of sedation, sedation efficacy, and adverse effects were recorded. Adverse effects were compared between patients receiving ketamine versus those who received ketamine and midazolam. Additional comparisons were made based on age and number of ketamine doses administered. RESULTS: Two hundred sixty-six patients were studied; 129 received ketamine and 137 patients received ketamine and midazolam. Time of sedation and efficacy of sedation were equivalent between groups. Overall, adverse effects with ketamine sedation included respiratory events (12 [4.5%]), vomiting (50 [18.7%]), emergence phenomena in the pediatric ED (71 [26.7%]), and emergence phenomena at home (60 [22.4%]). Significant emergence phenomena in the pediatric ED (ie, nightmares, hallucinations, and severe agitation) occurred in 7.1% of the ketamine group and in 6.2% of the ketamine-midazolam group, a rate difference of 0.8 (95% confidence interval [CI] -5.3 to 7.0). The addition of midazolam led to an increased incidence of oxygen desaturation events (ketamine 1.6% versus ketamine-midazolam 7.3%; rate difference -5.7, 95% CI -10.6 to -0.9) but a decreased incidence of vomiting (ketamine 19.4%, ketamine-midazolam 9.6%, rate difference 9.8, 95% CI 1.4 to 18.2). The incidence of emergence phenomena and significant emergence phenomena was not affected by the addition of midazolam. However, the addition of midazolam was associated with more agitation in the pediatric ED in children 10 years or older (ketamine 5.7% versus ketamine-midazolam 35.7%; rate difference -30.0, 95% CI -10.7 to -49.3). Age breakdown further showed 6.3% (95% CI 0.9 to 11.6) more episodes of oxygen desaturation in the ketamine-midazolam group in children younger than 10 years, and 12.1% (95% CI 1.5 to 22.6) more vomiting episodes in the ketamine group in children younger than 10 years. CONCLUSION: Ketamine and combined ketamine and midazolam provided equally effective sedation. The addition of midazolam did not alter the incidence of emergence phenomena. Vomiting occurred more frequently in the ketamine only group, whereas oxygen desaturation occurred more frequently in the ketamine-midazolam group. These findings were more pronounced in patients younger than 10 years. Parental and physician satisfaction remained high for all patients receiving intravenous ketamine sedation.