nils-herrmann/clean_scirepeval huggingface dataset:
Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl

In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and Cmax of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t 1/2,z of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t max was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6.
Sudden Hearing Loss in Patients with Chronic Hepatitis C Treated with Pegylated Interferon/Ribavirin

Sudden hearing loss has been reported on standard interferon (IFN)-α2 therapy. This is the first report on the occurrence of sudden hearing loss in six cases of chronic hepatitis C in temporal relation to treatment with pegylated (PEG)-IFN alfa2a or b/ribavirin combination therapy. Three patients were treated in an ongoing randomized placebo–controlled trial comparing the addition of 200 mg amantadine or placebo to the combination of 180 μg PEG-IFN α2a (PEGASYS®, Roche, Basel, CH)/wk and 1–1.2 g ribavirin/d (COPEGUS®, Roche, Nutley, USA) in de novo patients infected with HCV genotype 1. Sudden hearing loss and tinnitus developed on day 1 and after 4, 23, 25, 36, and 40 wk of treatment, respectively.Sudden hearing loss may occur in about 1% of patients on PEG-IFN/ribavirin combination therapy. This rate was not different to that observed in an untreated population. Possible mechanisms involved include direct ototoxicity of IFN, autoimmunity, and hematological changes. In contrast to published cases on auditory disability due to standard IFN, hearing loss did not fully resolve after discontinuation of therapy with PEG-IFN. On the other hand, symptoms did not worsen on continued treatment. Therefore, the decision whether to continue or to stop the treatment when signs of ototoxicity appear is based on the clinical judgment of the treating physician.
Neutrophil superoxide anion--generating capacity, endothelial function and oxidative stress in chronic heart failure: effects of short- and long-term vitamin C therapy.

First, we sought to study the effects of short- and long-term vitamin C therapy on oxidative stress and endothelial dysfunction in chronic heart failure (CHF), and second, we sought to investigate the role of neutrophils as a cause of oxidative stress in CHF.



Oxidative stress may contribute to endothelial dysfunction in CHF. Vitamin C ameliorates endothelial dysfunction in CHF, presumably by reducing oxidative stress, but this is unproven.



We studied 55 patients with CHF (ischemic and nonischemic etiologies) and 15 control subjects. Flow-mediated dilation (FMD) in the brachial artery was measured by ultrasound wall-tracking, neutrophil superoxide anion (O2-) generation by lucigenin-enhanced chemiluminescence and oxidative stress by measurement of free radicals (FRs) in venous blood using electron paramagnetic resonance (EPR) spectroscopy and plasma thiobarbituric acid reactive substances (TBARS). Measurements were performed at baseline in all subjects. The effects of short-term (intravenous) and long-term (oral) vitamin C therapy versus placebo were tested in patients with nonischemic CHF.



At baseline, FRs were higher in patients with CHF than in control subjects (p < 0.01), TBARS were greater (p < 0.005), neutrophil O2- -generating capacity was enhanced (p < 0.005) and FMD was lower (p < 0.0001). Compared with placebo, short-term vitamin C therapy reduced FR levels (p < 0.05), tended to reduce TBARS and increased FMD (p < 0.05), but did not affect neutrophil O2- -generating capacity. Long-term vitamin C therapy reduced FR levels (p < 0.05), reduced TBARS (p < 0.05) and improved FMD (p < 0.05), but also reduced neutrophil O2- -generating capacity (p < 0.05). Endothelial dysfunction was not related to oxidative stress, and improvements in FMD with vitamin C therapy did not relate to reductions in oxidative stress.



Oxidative stress is increased in ischemic and nonischemic CHF, and neutrophils may be an important cause. Vitamin C reduces oxidative stress, increases FMD and, when given long term, decreases neutrophil O2- generation, but the lack of a correlation between changes in endothelial function and oxidative stress with vitamin C implies possible additional non-antioxidant benefits of vitamin C.
Yoga's impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial.

To evaluate yoga's impact on inflammation, mood, and fatigue.



A randomized controlled 3-month trial was conducted with two post-treatment assessments of 200 breast cancer survivors assigned to either 12 weeks of 90-minute twice per week hatha yoga classes or a wait-list control. The main outcome measures were lipopolysaccharide-stimulated production of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), and scores on the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), the vitality scale from the Medical Outcomes Study 36-item Short Form (SF-36), and the Center for Epidemiological Studies-Depression (CES-D) scale.



Immediately post-treatment, fatigue was not lower (P > .05) but vitality was higher (P = .01) in the yoga group compared with the control group. At 3 months post-treatment, fatigue was lower in the yoga group (P = .002), vitality was higher (P = .01), and IL-6 (P = .027), TNF-α (P = .027), and IL-1β (P = .037) were lower for yoga participants compared with the control group. Groups did not differ on depression at either time (P > .2). Planned secondary analyses showed that the frequency of yoga practice had stronger associations with fatigue at both post-treatment visits (P = .019; P < .001), as well as vitality (P = .016; P = .0045), but not depression (P > .05) than simple group assignment; more frequent practice produced larger changes. At 3 months post-treatment, increasing yoga practice also led to a decrease in IL-6 (P = .01) and IL-1β (P = .03) production but not in TNF-α production (P > .05).



Chronic inflammation may fuel declines in physical function leading to frailty and disability. If yoga dampens or limits both fatigue and inflammation, then regular practice could have substantial health benefits.
Cholesterol lowering therapy inhibits the low-flow mediated vasoconstriction of the brachial artery in hypercholesterolaemic subjects.

1. We tested whether lipid lowering treatment with HMG CoA reductase inhibitor modified the flow mediated large artery reactivity in primary pure hypercholesterolaemia. 2. Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state. 3. Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40 mg orally) in 13 subjects and placebo in 15 others. 4. The significant decrease (P < 0.01) in diameter induced by wrist occlusion before (0.34 +/- 0.08 mm) placebo and pravastatin (0.39 +/- 0.10 mm) persisted after placebo (0.26 +/- 0.07 mm) but was abolished after pravastatin (0.07 +/- 0.05 mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin (P < 0.01) and lower after pravastin than after placebo (P < 0.05). Diameter during the wrist occlusion was higher after pravastatin than after placebo (4.35 +/- 0.16 vs 3.89 +/- 0.09 mm); P < 0.01). 5. These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol.
Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness.

This study determined the relative efficacy of aerobic exercise (daily walking) and moderate dietary sodium restriction (sodium intake <100 mmol/day) for reducing systolic blood pressure (SBP) and pulse pressure (PP) in postmenopausal women with elevated initial levels, and the potential role of reductions in large artery stiffness in these changes.



Lifestyle behaviors are recommended for lowering blood pressure (BP) in adults with elevated baseline levels, but there is little information as to the relative efficacy of different interventions or the mechanisms underlying their potential beneficial effects.



After baseline measurements and random assignment, 35 nonmedicated healthy postmenopausal women with SBP between 130 and 159 mm Hg completed three months of either aerobic (walking) exercise (n = 18; 62 +/- 9 years, mean +/- SD) or moderate dietary sodium restriction (SR) (n = 17; 65 +/- 10 years, mean +/- SD).



Body mass and composition, plasma volume, and fasting concentrations of metabolic coronary risk factors did not differ between the groups at baseline or change with intervention. Systolic BP and PP at rest decreased with both exercise and SR (p < 0.05); however, the reductions were three- to fourfold greater with SR (p < 0.05). Sodium restriction, but not exercise, also reduced 24-h SBP and PP (p < 0.05). Aortic pulse wave velocity (PWV) and carotid augmentation index were reduced only with SR (p < 0.05). Changes in SBP and PP at rest and over 24 h correlated with the corresponding changes in aortic PWV (r = 0.53 to 0.61, p < 0.01).



Moderate SR lowers SBP and PP in postmenopausal women with elevated baseline levels more than does daily walking. The greater blood pressure reductions with SR may be mediated in part by a decrease in the stiffness of the large elastic arteries.
Effects of a selective aldosterone blocker and thiazide-type diuretic on blood pressure and organ damage in hypertensive patients.

The aim of the present study was to compare the effects of the aldosterone blocker eplerenone and thiazide-like diuretic indapamide on blood pressure (BP) and target organs with reference to salt intake in hypertensive outpatients. Twenty hypertensive patients (nine women and 11 men, mean age 71 ± 13 years) with inadequate BP control despite taking calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) were administered eplerenone (50 mg/day) or indapamide (1 mg/day) for 3 months each in a randomized crossover manner. Salt intake, BP and indices of organ damage were assessed at baseline and at the end of each treatment period. Eplerenone and indapamide were similarly effective in lowering office and home BPs. Both the treatments significantly reduced the estimated glomerular filtration rate (eGFR) and increased serum uric acid levels. The treatment with eplerenone significantly increased serum potassium levels, whereas the treatment with indapamide significantly decreased them. The treatment with eplerenone significantly decreased pulse wave velocity and urinary 8-hydroxydeoxyguanosine levels. These changes were not significantly affected by the treatment with indapamide. In conclusion, eplerenone and indapamide were similarly effective in lowering office and home BPs in hypertensive patients treated with CCBs and ARBs. Eplerenone may exert more favorable effects on arterial stiffness and oxidative stress.
Differences in motor recruitment and resulting kinematics between low back pain patients and asymptomatic participants during lifting exertions.

Low back disorders are a prevalent problem in society today and may lead to chronic debilitating low back pain. Developing our understanding of temporal muscle and kinematic patterns during manual material handling tasks may provide insight for preventing the cascading series of events leading to chronic low back pain.



Sixty-two low back pain patients and 61 asymptomatic participants performed a variety of lifting exertions that varied in lift origin horizontal and vertical distance, lift asymmetry, and weight. Electromyographic activity of 10 trunk muscles as well as trunk and pelvic kinematics was recorded during each exertion. Differences in muscle activation and kinematic parameters were compared between low back pain patients and asymptomatic participants as a function of experimental conditions.



Both the left and right erector spinae activated significantly earlier and were on significantly longer in low back pain patients compared to asymptomatic participants. The horizontal and vertical location of the lift influenced the EMG and kinematic differences between the low back pain patients and asymptomatic participants.



These finding indicate that low back pain patients would be exposed to increase muscle activity resulting in higher spine loads for a greater length of time compared to asymptomatic participants. The longer exposure time to increased spine load may lead to greater risk of future low back injury and cascading events leading to debilitating low back pain. The longer muscle activation time suggests that low back pain patients have changed their motor program from an open to a closed loop system.
Central role for ENaC in development of hypertension.

Na(+) reabsorption by the epithelial Na(+) channel (ENaC) in cortical collecting duct provides the final renal adjustment to Na(+) balance, there being no further downstream Na(+) transport system. This fact coupled with the responsiveness of ENaC to aldosterone, which conveys stimulation inversely proportional to the state of Na(+) balance, places ENaC in a pivotal position to influence the risk for hypertension. Although several molecular variants of ENaC subunits have been identified, there has been no consistent demonstration of an association of any of the variants with hypertension. More compelling is the notion that ENaC activity does not fully adjust to an increase in Na(+) reabsorption occurring elsewhere in the nephron, there being overstimulation by inappropriately elevated aldosterone levels. Additional evidence that the maintenance of hypertension can be dependent on ENaC is derived from the observed responses to the treatment of hypertensive individuals with inhibitors of ENaC. Described is a clinical trial in which black hypertensive individuals who did not fully respond to more traditional therapy were given amiloride, spironolactone, a combination of the two drugs, or placebo. Treatment with either of the active inhibitors of ENaC resulted in a substantial improvement in BP. In conclusion, evidence to date is supportive of the concept that an increase in Na(+) transport by ENaC may be a common and requisite component of salt-dependent forms of hypertension.
New strategies to detect alcohol use disorders in the preoperative assessment clinic of a German university hospital.

Although alcohol use disorders (AUDs) have enormous public health consequences, the rate of diagnosis of AUDs remains unsatisfactorily low. The primary aim of this study was to compare the detection of AUDs by anesthesiologists in a large preoperative assessment clinic to that by computerized self-assessment of the Alcohol Use Disorder Identification Test. Secondary outcome measures were to compare the actions taken by anesthesiologists upon a finding of an AUD.



One thousand five hundred fifty-six patients were included. Before preoperative assessment, patients were asked to complete the Alcohol Use Disorder Identification Test (positive scores: men > or = 8, women > or = 5) using a computer. The authors performed a retrospective chart analysis of the anesthesiologists' actions upon a finding of an AUD. The anesthesiologists were blinded to the results of the computer-based assessment and to the subsequent chart analysis.



The prevalence rate of AUDs determined by the anesthesiologists was 6.9% (107 of 1,556), whereas the proportion of patients positive for an AUD using the computerised Alcohol Use Disorder Identification Test was 18.1% (282 of 1,556) (P < 0.001). The detection rate by the anesthesiologists of AUDs among men was significantly higher than among women (P < 0.001) as well as in the elderly compared with younger patients (P < 0.001). Action taken by anesthesiologists was mainly based on evaluating quantity of alcohol consumption.



The computer-based self-assessment increases detection rates of AUDs in busy settings such as a preoperative assessment clinic. Prevalence rates of AUDs are underestimated. Best-practice guidelines for detection of AUDs are not implemented in the daily clinical routine. Barrier analysis is urgently required.
Clozapine eligibility among state hospital patients.

State Hospital's entire resident population (n = 1,300) was screened on an arbitrary target day to determine eligibility for clozapine. Sixty percent of 803 patients with schizophrenia or schizoaffective disorder diagnoses met Food and Drug Administration (FDA)- approved criteria for clozapine use as judged by review of past medication trial records and by the responsible physicians. Eighty-eight percent of these patients were medically cleared, and of those cleared, 63 percent agreed to clozapine treatment. Of the patients who began a clozapine trial, 76 percent were still taking the drug 12 months later. Preliminary findings from a randomized trial of clozapine versus usual care (n = 227) indicate that discharge rates associated with clozapine and usual care do not differ. Once discharged, however, patients assigned to clozapine are less likely to be readmitted. Hence, clozapine may be more cost-effective than usual care. However, before savings can be realized, State governments will have to make up-front investments of approximately $140 million simply to give patients hospitalized on a single day a year's access to clozapine.
Epidural lysis of adhesions for failed back surgery and spinal stenosis: factors associated with treatment outcome.

Failed back surgery syndrome (FBSS) is a challenging problem. One treatment advocated to treat FBSS is epidural lysis of adhesions (LOA). The results of studies examining LOA for FBSS have been mixed, but are limited because no study has ever sought to identify factors associated with outcomes.



We performed this multicenter, retrospective study in 115 patients who underwent LOA for FBSS (n = 104) or spinal stenosis (n = 11) between 2004 and 2007. Twenty-seven demographic, clinical, and procedural variables were extracted from medical records and correlated with the outcome, defined as ≥50% pain relief lasting ≥1 month. Univariable analysis was performed, followed by multivariable logistic regression.



Overall, 48.7% (95% confidence interval [CI], 39.3%-58.1%) of patients experienced a positive outcome. In univariable analysis, those who had a positive outcome were older (mean age 64.1 years; 95% CI, 59.7-68.6 vs 57.2; 95% CI, 53.0-61.4 years; P = 0.02), while higher baseline numerical rating scale pain scores were associated with a negative outcome (mean 6.7 years; 95% CI, 6.0-7.3 vs 7.5; 95% CI, 6.9-8.0; P = 0.07). Use of hyaluronidase did not correlate with outcomes in univariable analysis (odds ratio [OR], 1.2; 95% CI, 0.6-2.5; P = 0.65). In multivariable analysis, age ≥81 years (OR, 7.8; 95% CI, 1.4-53.7), baseline numerical rating scale score ≤9 (OR, 4.4; 95% CI, 1.4-16.3, P = 0.02), and patients on or seeking disability or worker's compensation (OR, 4.4; 95% CI, 1.1-19.5, P = 0.04) were significantly more likely to experience a positive outcome.



Considering our modest success rate, selecting patients for epidural LOA based on demographic and clinical factors may help better select treatment candidates. Procedural factors such as the use of hyaluronidase that increase risks and costs did not improve outcomes, so further research is needed before these become standard practice.
Spanish version of the Parkinson’s Disease Questionnaire–Carer (PDQ-Carer)

Parkinson's caregivers are frequently affected by a range of physical and psychological factors affecting to the quality of life (QoL) of patients and caregivers. However, while there are well-validated QoL instruments for patients, few specific measures has been developed for caregivers of patients with PD. This study examined the psychometric properties of the Spanish version of the Parkinson Disease Questionnaire-Carer (PDQ-Carer) for use in PD caregivers.



The PDQ-Carer and the Short Form-36 Health Survey (SF-36) were completed by sample of 73 caregivers of patients with PD in Spain (71.8 % females; 63.6 ± 12.3 years old).



Psychometric analysis confirmed the reliability and validity of the Spanish version of the PDQ-Carer. The internal consistency was found to be satisfactory for the four PDQ-Carer domains: Personal and Social Activities, Depression and Anxiety, Self-care and Stress with Cronbach's alpha values ranging 0.80 to 0.95. The PDQ-Carer was significantly correlated with the eight SF-36 domains (r = -0.31 to -0.59, p < 0.001) supporting the concurrent validity of the instrument.



Overall, these results provide preliminary evidence of the utility of the Spanish version of the PDQ-Carer in non-professionals caregivers.
The feasibility of patient-controlled paravertebral analgesia for major breast cancer surgery: a prospective, randomized, double-blind comparison of two regimens.

Paravertebral analgesia is useful for breast surgery. Patient controlled analgesia by IV or epidural routes is well established for delivering postoperative analgesia. Our objective was to apply patient control to paravertebral analgesia and evaluate the efficacy and tolerability of two distinct dosing regimens.



Patients undergoing major breast cancer surgery were recruited for this prospective, double-blind, randomized trial of two patient-controlled paravertebral analgesia regimens: 19 patients received levobupivacaine 0.2% at 8 mL/h with 3-mL bolus and 15-min lockout (15-min lockout group); 18 received levobupivacaine 0.2% at 4 mL/h with 8-mL bolus and 30-min lockout (30-min lockout group). Our primary outcome was dynamic pain scores (visual analog scale) at 4-hourly intervals for 36 h. Secondary outcomes were resting pain scores, rescue analgesia requirements, volume of levobupivacaine administered, demands for levobupivacaine, levobupivacaine boluses received, and patient satisfaction.



Resting and dynamic pain scores were comparable in the groups. Two 15-min lockout patients and five 30-min lockout patients required rescue analgesia (P = 0.23). Patients received 400 +/- 95 mL and 330 +/- 130 mL levobupivacaine in 15-min and 30-min lockout groups, respectively (P = 0.012). The 15-min lockout group requested a bolus 75 +/- 16 times; the 30-min lockout group requested it 69 +/- 14 times (P = 0.40). However, the 15-min lockout group received 39 +/- 22 boluses and the 30-min lockout group only 24 +/- 16 (P = 0.02). Systolic pressure, heart rate, respiratory rate, sedation scores, nausea, antiemetic requirement, and satisfaction scores were similar in each group.



Patient-controlled paravertebral analgesia for breast cancer surgery, with either regimen, provided satisfactory analgesia and was well tolerated.