Effect of 3-Hydroxy-3-Methylglutaric Acid Administration on Bile Lipid Composition in Humans

The effects of the lipid-lowering agent 3-hydroxy-3-methylglutaric acid (HMGA) on serum lipids and on biliary lipid composition were evaluated in a double-blind, placebo-controlled study in normolipidemic volunteers. After 4 weeks of HMGA administration (1 g three times a day orally) serum total cholesterol showed a significant decrease with regard to both pretreatment values and corresponding values of controls. The bile lipid molar percentage composition and the cholesterol saturation index showed no modification after HMGA and did not differ from the values obtained in the placebo group. These findings indicate that HMGA exerts no adverse effects on bile lipid composition in humans, differing from other hypolipidemic drugs currently in clinical use, which increase the bile cholesterol saturation index.     

Effect of Ursodeoxycholic Acid Administration after Liver Transplantation on Serum Liver Tests and Biliary Complications: A Randomized Clinical Trial

Background/Aims: Endogenous hydrophobic bile acids are suspected to be one of the pathogenetic factors of biliary complications after orthotopic liver transplantation (OLT). This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA) administration early after OLT on serum liver tests and the incidence of biliary complications. Methods: 112 adult patients undergoing OLT from donation after cardiac death (DCD) were randomized to UDCA (13-15 mg/kg/day for 4 weeks; 56 patients) or placebo (56 patients). Serum liver tests and serum bile acids of all patients and biliary bile acids in patients with T-tube drainage were determined during the 4 weeks after OLT. Biliary complications as well as patient and graft survival were analyzed during a mean follow-up of 41.6 months. Results: UDCA treatment decreased ALT, AST and GGT (p < 0.05) during the 4 weeks after OLT and the incidence of biliary sludge and casts within the 1st year (p < 0.05). However, no differences in the incidence of other biliary complications as well as 1-, 3- and 5-year graft and patient survival were observed. Conclusions: UDCA administration early after DCD-OLT improves serum liver tests and decreases the incidence of biliary sludge and casts within the 1st postoperative year but does not affect overall outcome up to 5 years after OLT.     

Effect of Profound Acid Suppression in Functional Dyspepsia: a Double-Blind,Randomized, Placebo-Controlled Trial

Background: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. Methods: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d ( n = 100) or placebo ( n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. Results: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% CI of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. Conclusion: A subset of patients with FD will respond to therapy with omeprazole.     

Comparison of Three Bile Acid Provocation Tests: Intravenous Cholecystokinin,a Standard Test Meal,and an Oral Bile Acid Load in Healthy Subjects

Three different bile acid provocation tests—an intravenous stimulation with cholecystokinin (CCK), a test meal, and an oral bile acid load of 500 mg chenodeoxycholic acid (CDAF—were compared in 12 healthy subjects. Blood samples were drawn every 30min for 3 h, and serum bile acids (SBA) were measured by an enzymatic method (Enzabile®). The CCK stimulation gave significant SB A elevations only at 30 min. After the test meal and the CDA loading tests SB A elevations were observed from 30 min and throughout the observation period. Maximal increases were obtained at 120 min after the test meal but already at 30 min after the CDA loading test. We conclude that among these three bile acid provocation tests the oral CDA loading test is to be preferred because it gives marked and rapid elevation of SBA in all subjects and is independent of bile acid pool size and normal function of the gallbladder.     

Effect of Amiloride and Spironolactone on Renal Tubular Function,Ambulatory Blood Pressure,and Pulse Wave Velocity in Healthy Participants in a Double-Blinded,Randomized, Placebo-Controlled,Crossover Trial

We wanted to test the hypothesis that treatment with amiloride or spironolactone reduced ambulatory (ABP) and central blood pressure (CBP) and that tubular transport via ENaCγ and AQP2 was increased after furosemide treatment. During baseline conditions, there were no differences in ABP, CBP, renal tubular function, or plasma concentrations of vasoactive hormones. After furosemide treatment, an increase in CBP, CH₂o, FE_Na, FE_K, u-AQP2/min, u-ENaCγ/min, PRC, p-Ang II, and p-Aldo was observed. The increases in water and sodium absorption via AQP2 and ENaC after furosemide treatment most likely are compensatory phenomena to antagonize water and sodium depletion.     

Synergistic Effect by Co‐Administration of Tamsulosin and Solifenacin on Bladder Activity in Rats

Objectives: We examined the effects of alpha1‐adrenoceptor antagonist (tamsulosin hydrochloride) and antimuscarinic agent (solifenacin succinate) alone or in combination on the urinary adenosine triphosphate (ATP) level and cystometric parameters before and after bladder stimulation. Methods: Female rats were administered tamsulosin hydrochloride (0.5 or 3 µg/kg/h) and/or solifenacin succinate (20 or 100 µg/kg/h) via a subcutaneously implanted osmotic minipump. Rats receiving distilled water were used as control. After 2 weeks, continuous cystometry with physiological saline or 0.1% acetic acid solution was performed. Urinary ATP level was also measured before and after stimulation by 0.1% acetic acid solution. Results: During cystometry with bladder stimulation, the interval between voiding became shorter and the maximum voiding pressure (MVP) became higher in the control group. In the high‐dose tamsulosin and solifenacin groups, the inhibition of urinary frequency was observed. The MVP also became higher in the high‐dose tamsulosin group, but such a change was not seen in the high‐dose solifenacin group. In case of low‐dose administration, either agent alone did not inhibit the increase of urinary frequency and MVP due to bladder stimulation. However, co‐administration of these ineffective low doses of tamsulosin and solifenacin resulted in the inhibition of urinary frequency. The high‐dose or low‐dose solifenacin group and the co‐administration group showed similar inhibition of the increase of urinary ATP after bladder stimulation. Conclusion: Tamsulosin may have a different effect on the bladder and/or the neuronal pathways that is unrelated to ATP, so the combination of tamsulosin and solifenacin may synergistically inhibit urinary frequency after bladder stimulation.     

Effects of a Multicomponent Cognitive Behavioral Group Intervention on Fear of Falling and Activity Avoidance in Community-Dwelling Older Adults: Results of a Randomized Controlled Trial

OBJECTIVES: To evaluate the effects of a multicomponent cognitive behavioral intervention on fear of falling and activity avoidance in older adults.
DESIGN: Randomized controlled trial.
SETTING: Community-dwelling adults in the Netherlands.
PARTICIPANTS: Five hundred forty adults aged 70 and older who reported fear of falling and fear-induced activity avoidance (280 intervention, 260 control).
INTERVENTION: A multicomponent cognitive behavioral group intervention consisting of eight weekly sessions and a booster session. The sessions were aimed at instilling adaptive and realistic views on falls, reducing fall risk, and increasing activity and safe behavior.
MEASUREMENTS: Data on fear of falling, activity avoidance, concerns about falling, perceived control over falling, and daily activity were collected at baseline and at 2, 8, and 14 months.
RESULTS: At 2 months, there were significant between-group differences in fear of falling (odds ratio (OR)=0.11; P <.001), activity avoidance (OR=0.26; P <.001), concerns about falling (adjusted mean difference=−1.51; P =.02), and daily activity (adjusted mean difference=0.95; P =.01). At 8 months, there were significant between-group differences in all outcomes and at 14 months in fear of falling ( P =.001), perceived control over falling ( P =.001), and recurrent fallers ( P =.02) but not in activity avoidance ( P =.07), concerns about falling ( P =.07), daily activity ( P =.24), or fallers ( P =.08).
CONCLUSION: This multicomponent cognitive behavioral intervention showed positive and durable effects on fear of falling and associated activity avoidance in community-dwelling older adults. Future research should focus on improving intervention uptake and adherence, reaching frailer populations, and determining potential intervention effects on functional outcomes.     

Long-Term Effect on Mortality of a Home Intervention that Reduces Functional Difficulties in Older Adults: Results from a Randomized Trial

OBJECTIVES: To evaluate the long-term mortality effect of a home-based intervention previously shown to reduce functional difficulties and whether survivorship benefits differ according to initial mortality risk level.
DESIGN: Two-group randomized trial with survivorship followed up to 4 years from study entry.
SETTING: Homes of urban community-living elderly people.
PARTICIPANTS: Three hundred nineteen adults aged 70 and older with difficulties performing daily activities.
INTERVENTION: Occupational and physical therapy sessions to instruct participants in compensatory strategies, home modifications, home safety, fall recovery techniques, and balance and muscle strength exercises.
MEASUREMENTS: Survival time was number of days between baseline interview and date of death, as determined using data from the National Death Index or December 31, 2005. Participants were stratified according to baseline mortality risk (low, moderate, high) using a prognostic indicator.
RESULTS: At 2 years, intervention participants (n=160) had a 5.6% mortality rate (n=9 deaths) and controls (n=159) a 13.2% rate (n=21 deaths; P =.02). Mortality rates remained lower for intervention participants up to 3.5 years from study entry. At 2 years, intervention participants with moderate mortality risk had a 16.7% mortality rate (n=16 deaths/96), compared with 28.2% for equivalent control group participants (n=24 deaths/85; P =.02). By 3 years, mortality rates were not statistically significantly different between the experimental and control groups.
CONCLUSIONS: The intervention extended survivorship up to 3.5 years and maintained statistically significant differences for 2 years. Subjects at moderate mortality risk derived the most intervention benefit. Findings suggest that the intervention could be a low-cost clinical tool to delay functional decline and mortality.     

Effect of Fish Oil Supplementation on Quality of Life in a General Population of Older Dutch Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVES: To investigate the effect of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation on quality of life (QOL).
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: Independently living individuals from the general older Dutch population.
PARTICIPANTS: Three hundred two individuals aged 65 and older without depression or dementia.
INTERVENTION: 1,800 mg/d EPA-DHA (n=96), 400 mg/d EPA-DHA (n=100), or placebo capsules (n=106) for 26 weeks.
MEASUREMENTS: QOL was assessed using the short version of the World Health Organization QOL questionnaire (WHOQOL-BREF). The WHOQOL-BREF covers four domains: physical health, psychological health, social relationships, and satisfaction with environment. The total score range is 26 to 130, with higher scores indicating a more favorable condition.
RESULTS: Mean age of the participants was 70, and 55% were male. Plasma concentrations of EPA-DHA increased 238% in the high-dose and 51% in the low-dose EPA-DHA group, reflecting excellent adherence. Median baseline total WHOQOL scores ranged from 107 to 110 in the three groups and were not significantly different from each other. After 26 weeks, the mean difference from placebo was −1.42 (95% confidence interval (CI)=−3.40–0.57) for the high-dose and 0.02 (95% CI=−1.95–1.99) for the low-dose fish oil group. Treatment with 1,800 mg or 400 mg EPA-DHA did not affect total QOL or any of the separate domains after 13 or 26 weeks of intervention.
CONCLUSION: Supplementation with high or low doses of fish oil for 26 weeks did not influence the QOL of healthy older individuals.     

Effect of Using a Wheeled Walker on Physical Activity and Sedentary Time in People with Chronic Obstructive Pulmonary Disease: A Randomised Cross-Over Trial

Purpose

To determine the effects of providing a wheeled walker (WW) for use in the home and community, on daily physical activity (PA) and sedentary time (ST) in people with chronic obstructive pulmonary disease (COPD).

Methods

A randomised cross-over study in which participants with COPD characterised by a 6-min walk distance ≤ 450 m, who had recently finished pulmonary rehabilitation, completed two 5-week phases. During one phase, participants were provided a WW to use, whereas during the other phase, the WW was not available. The order of the phases was randomised. For the final week of each phase, measures of PA and ST were collected using wearable devices and health-related quality of life was measured using the Chronic Respiratory Disease Questionnaire (CRDQ). Wheeled walker use was also measured using an odometer attached to the device.

Results

17 participants [FEV₁ = median (interquartile range) 33 (25) % pred; ten males] aged mean (SD) 73 (9) years completed the study. Comparing the data collected when the WW was not available for use, the daily step count was greater (mean difference [MD] 707 steps/day (95% confidence interval [CI] 75 to 1340) and participants tended to report less dyspnoea during daily life (MD 0.5 points per item, 95% CI − 0.1 to 1.0) when WW was available. No differences were observed for ST, upright time or stepping time. The WW was used over 4504 m/week (95% CI 2746 to 6262).

Conclusion

These data demonstrated that, when provided to selected patients with COPD, WWs increased daily step count.

Clinical trial registration number: ACTRN12609000332224.

     

Improving Effect of Ellagic Acid on Sleep Quality and Gastrointestinal Symptoms in Patient With Irritable Bowel Syndrome: Randomized Double-Blind Clinical Trial

Background: The quality of sleep in people with irritable bowel syndrome (IBS) is reduced by increased oxidative stress and clinical problems. Assessing the effects of ellagic acid (EA) on sleep quality and gastrointestinal symptoms in patients with IBS was the aim of this study. Methods: In this research that was conducted as a randomized, double-blind, placebo-controlled clinical trial, 44 patients with IBS were enlisted. Individuals approved by the project clinical counselor were divided into two intervention groups to receive 180 mg of EA per day (n = 22) and a placebo group (n = 22) for 2 months. Petersburg’s Sleep Quality (PSQI) questionnaire and IBS severity score system (IBSSS) were assessed at the beginning and end of the study. Statistical analysis was performed using SPSS software.Results: At the end of the study, changes in mean PSQI and scores related to sleep subgroups were significant between the two groups (P < .05). Also, the significant changes were not seen in sleep and sleep subgroups scores in the placebo group at the end of the study (P > .05). EA consumption reduced IBSSS score and IBS symptoms in the intervention group after 2 months (P < .05).Discussion: The results arisen from this study indicated that receiving EA had a beneficial effect on sleep quality and gastrointestinal symptoms in IBS patients. The antioxidant and anti-inflammatory properties of EA may be responsible for these beneficial effects.     

Effect of Amiloride and Spironolactone on Renal Tubular Function and Central Blood Pressure in Patients with Arterial Hypertension during Baseline Conditions and after Furosemide: A Double-Blinded,Randomized, Placebo-Controlled Crossover Trial

This study demonstrates that the increased potassium content in the body seems to change both the blood pressure and renal tubular function. We wanted to test the hypotheses that amiloride and spironolactone induced potassium retention reduces ambulatory blood pressure (ABP) and central blood pressure (CBP) during baseline conditions and after furosemide and that the tubular transport via the epithelial sodium channels (ENaCs) and aquaporin-2 (AQP2) water channels was increased by furosemide in arterial hypertension. Each of three 28-day treatment periods (placebo, amiloride, and spironolactone) was completed by a 4-day period with standardized diet regarding calories and sodium and water intake. At the end of each period, we measured pulse wave velocity (PWV), central systolic blood pressure (CSBP), central diastolic blood pressure (CDBP), glomerular filtration rate (GFR), free water clearance (C_H2O), fractional excretion of sodium (FE_Na) and potassium (FE_K), urinary excretion of AQP2 (u-AQP2), urinary excretion of γ-fraction of the ENaC (u-ENaCγ), and plasma concentrations of renin (PRC), angiotensin II (p-Ang II), and aldosterone (p-Aldo) at baseline conditions and after furosemide bolus. Ambulatory blood pressure and CBP were significantly lowered by amiloride and spironolactone. During 24-hour urine collection and at baseline, GFR, C_H2O, FE_Na, FE_K, u-AQP2 and u-ENaCγ were the same. After furosemide, C_H2O, FE_Na, FE_K, u-AQP2, u-ENaCγ, PRC, p-Ang II, p-Aldo, PWV and CDBP increased after all treatments. However, during amiloride treatment, FE_K increased to a larger extent than after spironolactone and during placebo after furosemide, and CSBP was not significantly reduced. The increases in water and sodium absorption via AQP2 and ENaC after furosemide most likely are compensatory phenomena to antagonize water and sodium depletion. Amiloride is less effective than spironolactone to reduce renal potassium excretion.

Trial registration: ClinicalTrials.gov identifier: NCT0138088.     

Patient Anxiety and Depression Moderate the Effects of Increased Self-management Knowledge on Physical Activity: A Secondary Analysis of a Randomised Controlled Trial on Health-Mentoring in COPD

Objective. Anxiety and depression are common comorbidities in people with chronic obstructive pulmonary disease (COPD). While these comorbidities could potentially lead to a higher motivation to learn about self-management, they could also inhibit patients from translating this knowledge into appropriate self-management behaviours. This paper explores the moderating effects of anxiety and depression on a health-mentoring intervention, focusing on mechanisms of change (mediation). Methods. 182 COPD patients participated in an RCT, with anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HADS), self-management knowledge by the Partners in Health Scale, and spontaneous physical activity using accelerometers, all measured at baseline, 6 and 12 months. The moderated mediation model tested the intervention's effect on physical activity, mediated via changes in self-management knowledge, at different levels of anxiety and depression. Results. Knowledge mediated the effect of the intervention on changes in physical activity only for participants reporting low levels of anxiety or depression. Both acted as moderators: Increased knowledge led to more physical activity among participants reporting low anxiety or depression and to less activity among highly anxious or depressed participants. Conclusion. Although health-mentoring interventions can be an effective tool to increase knowledge and physical activity among COPD patients, it is essential to take anxiety and depression into account, as increased knowledge may have detrimental effects in highly anxious or depressed participants. This suggests that patients with elevated anxiety or depression may need to be treated appropriately before engaging in chronic disease self-management interventions.