Attenuated nicotine‐like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily

PubMed Central

Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

2016-01-01

Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

Short daily hemodialysis is associated with lower plasma FGF23 levels when compared with conventional hemodialysis

PubMed Central

Zaritsky, Joshua; Rastogi, Anjay; Fischmann, George; Yan, Jieshi; Kleinman, Kenneth; Chow, Georgina; Gales, Barbara; Salusky, Isidro B.; Wesseling-Perry, Katherine

2014-01-01

Background The utilization of short-term daily hemodialysis has increased over the last few years, but little is known on its effects on the control of serum phosphate and fibroblast growth factor 23 (FGF23) levels. Methods We therefore performed a cross-sectional study to compare FGF23 levels as well as other biochemical variables between 24 patients undergoing short daily hemodialysis using the NxStage System® and 54 patients treated with conventional in-center hemodialysis. FGF23 levels were measured using the second-generation Immutopics® C-terminal assay. Results Short daily hemodialysis patients were younger than patients on conventional hemodialysis but there were no differences between groups in the duration of end-stage renal disease nor in the number of patients with residual renal function. A greater number of short daily hemodialysis patients received vitamin D sterol therapy than did conventional in-center hemodialysis patients while there were no differences in the use of different phosphate binders and calcimimetic therapy between groups. Overall serum calcium, phosphorus and intact parathyroid hormone levels were similar between groups. While serum phosphorus levels correlated with FGF23 concentrations in each group separately [r = 0.522 (P < 0.01) and r = 0.42 (P < 0.01) in short daily and conventional in-center hemodialysis, respectively], FGF23 levels were lower [823 RU/mL (263, 2169)] in the patients receiving short daily hemodialysis than in patients treated with conventional hemodialysis [2521 RU/mL (909, 5556)] (P < 0.01 between groups). Conclusions These findings demonstrate that FGF23 levels are significantly lower in short daily hemodialysis patients and suggest that FGF23 levels may be a more sensitive biomarker of cumulative phosphate burden than single or multiple serum phosphorus determinations in patients treated with hemodialysis. PMID:24009282

Short daily hemodialysis is associated with lower plasma FGF23 levels when compared with conventional hemodialysis.

PubMed

Zaritsky, Joshua; Rastogi, Anjay; Fischmann, George; Yan, Jieshi; Kleinman, Kenneth; Chow, Georgina; Gales, Barbara; Salusky, Isidro B; Wesseling-Perry, Katherine

2014-02-01

The utilization of short-term daily hemodialysis has increased over the last few years, but little is known on its effects on the control of serum phosphate and fibroblast growth factor 23 (FGF23) levels. We therefore performed a cross-sectional study to compare FGF23 levels as well as other biochemical variables between 24 patients undergoing short daily hemodialysis using the NxStage System® and 54 patients treated with conventional in-center hemodialysis. FGF23 levels were measured using the second-generation Immutopics® C-terminal assay. Short daily hemodialysis patients were younger than patients on conventional hemodialysis but there were no differences between groups in the duration of end-stage renal disease nor in the number of patients with residual renal function. A greater number of short daily hemodialysis patients received vitamin D sterol therapy than did conventional in-center hemodialysis patients while there were no differences in the use of different phosphate binders and calcimimetic therapy between groups. Overall serum calcium, phosphorus and intact parathyroid hormone levels were similar between groups. While serum phosphorus levels correlated with FGF23 concentrations in each group separately [r=0.522 (P<0.01) and r=0.42 (P<0.01) in short daily and conventional in-center hemodialysis, respectively], FGF23 levels were lower [823 RU/mL (263, 2169)] in the patients receiving short daily hemodialysis than in patients treated with conventional hemodialysis [2521 RU/mL (909, 5556)] (P<0.01 between groups). These findings demonstrate that FGF23 levels are significantly lower in short daily hemodialysis patients and suggest that FGF23 levels may be a more sensitive biomarker of cumulative phosphate burden than single or multiple serum phosphorus determinations in patients treated with hemodialysis.

Effect of lacosamide on the steady-state pharmacokinetics of digoxin: results from a phase I, multiple-dose, double-blind, randomised, placebo-controlled, crossover trial.

PubMed

Cawello, Willi; Mueller-Voessing, Christa; Andreas, Jens-Otto

2014-05-01

Recent data suggest that P-glycoprotein may be involved in cellular transport of lacosamide. To investigate potential drug-drug interactions (DDIs) between lacosamide and digoxin, this phase I, multiple-dose, randomised, double-blind, placebo-controlled, crossover trial assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of digoxin administered in combination with lacosamide or placebo. Twenty healthy White male volunteers were randomised. After receiving digoxin 0.25 mg three times daily on day 1 (loading dose), participants received digoxin 0.25 mg once daily on days 2-22. Participants received either lacosamide (200 mg twice daily) or placebo on days 8-11 and vice versa on days 18-21, after a 6-day washout. The steady-state area under concentration-time curve over the dosing interval (AUC(24,ss)) and maximum steady-state plasma concentration (C(max,ss)) of digoxin were measured; ratios of these parameters for co-administration of digoxin + lacosamide versus digoxin alone were used to evaluate potential DDIs. Interaction was excluded if the 90 % confidence interval (CI) for the geometric mean ratio of AUC24,ss and C max,ss fell within the acceptance range for bioequivalence (0.8-1.25). The point estimates (90 % CI) of the geometric mean ratios for co-administration of digoxin with lacosamide versus digoxin alone for AUC(24,ss) [1.024 (0.979-1.071)] and C(max,ss) [1.049 (0.959-1.147)] were within the acceptance range for bioequivalence. Digoxin and lacosamide co-administration was generally well-tolerated. A small numerical increase in the mean PR interval following co-administered digoxin + lacosamide was observed versus digoxin alone and versus pre-treatment baseline values (178.5 vs. 170.4 or 166.8 ms, respectively). The RR interval increased in parallel. The change was not considered clinically relevant. Co-administration of steady-state digoxin (0.25 mg/day) with multiple-dose lacosamide (400 mg/day) versus digoxin alone revealed no differences in digoxin disposition.

Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects

PubMed Central

Frost, Charles; Nepal, Sunil; Wang, Jessie; Schuster, Alan; Byon, Wonkyung; Boyd, Rebecca A; Yu, Zhigang; Shenker, Andrew; Barrett, Yu Chen; Mosqueda-Garcia, Rogelio; LaCreta, Frank

2013-01-01

Aim Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban. Method This double-blind, randomized, placebo-controlled, parallel group, multiple dose escalation study was conducted in six sequential dose panels – apixaban 2.5, 5, 10 and 25 mg twice daily and 10 and 25 mg once daily– with eight healthy subjects per panel. Within each panel, subjects were randomized (3:1) to oral apixaban or placebo for 7 days. Subjects underwent safety assessments and were monitored for adverse events (AEs). Blood samples were taken to measure apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and modified prothrombin time (mPT). Results Forty-eight subjects were randomized and treated (apixaban, n = 36; placebo, n = 12); one subject receiving 2.5 mg twice daily discontinued due to AEs (headache and nausea). No dose limiting AEs were observed. Apixaban maximum plasma concentration was achieved ∼3 h post-dose. Exposure increased approximately in proportion to dose. Apixaban steady-state concentrations were reached by day 3, with an accumulation index of 1.3–1.9. Peak : trough ratios were lower for twice daily vs. once daily regimens. Clotting times showed dose-related increases tracking the plasma concentration–time profile. Conclusion Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures. PMID:23451769

Influence of Fractionation Scheme and Tumor Location on Toxicities After Stereotactic Body Radiation Therapy for Large (≥5 cm) Non-Small Cell Lung Cancer: A Multi-institutional Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, Vivek; Shostrom, Valerie K.; Zhen, Weining

Purpose: To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. Methods: Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. Results: Ninety-two patients from 12 institutionsmore » were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). Conclusions: From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities.« less

Influence of Fractionation Scheme and Tumor Location on Toxicities After Stereotactic Body Radiation Therapy for Large (≥5 cm) Non-Small Cell Lung Cancer: A Multi-institutional Analysis.

PubMed

Verma, Vivek; Shostrom, Valerie K; Zhen, Weining; Zhang, Mutian; Braunstein, Steve E; Holland, John; Hallemeier, Christopher L; Harkenrider, Matthew M; Iskhanian, Adrian; Jabbour, Salma K; Attia, Albert; Lee, Percy; Wang, Kyle; Decker, Roy H; McGarry, Ronald C; Simone, Charles B

2017-03-15

To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. Ninety-two patients from 12 institutions were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities. Copyright © 2016 Elsevier Inc. All rights reserved.

Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection-embryo transfer cycle.

PubMed

Kahraman, Korhan; Berker, Bulent; Atabekoglu, Cem Somer; Sonmezer, Murat; Cetinkaya, Esra; Aytac, Rusen; Satiroglu, Hakan

2009-06-01

To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. Prospective, randomized, clinical study. University hospital. Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.

Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease.

PubMed

Yun, Ji Young; Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon; Jeon, Beomseok

2017-01-01

This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

PubMed Central

Cui, Yimin; Song, Yan; Wang, Jessie; Yu, Zhigang; Schuster, Alan; Barrett, Yu Chen; Frost, Charles

2013-01-01

Background The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. PMID:24353445

Transgenerational effects of adolescent nicotine exposure in rats: Evidence for cognitive deficits in adult female offspring.

PubMed

Renaud, Samantha M; Fountain, Stephen B

2016-01-01

This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0mg/kg nicotine or an equivalent volume of saline for 35days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment. Half of the offspring of F0 nicotine-exposed breeders and half of the offspring of F0 saline control rats received twice-daily i.p. injections of 1.0mg/kg nicotine during adolescence on P25-59. The remainder of the rats received twice-daily saline injections for the same period. To evaluate transgenerational effects of nicotine exposure on complex cognitive learning abilities, F1 generation rats were trained to perform a highly structured serial pattern in a serial multiple choice (SMC) task. Beginning on P95, rats in the F1 generation were given either 4days of massed training (20patterns/day) followed by spaced training (10 patterns/day) or only spaced training. Transgenerational effects of adolescent nicotine exposure were observed as greater difficulty in learning a "violation element" of the pattern, which indicated that rats were impaired in the ability to encode and remember multiple sequential elements as compound or configural cues. The results indicated that for rats that received massed training, F1 generation rats with adolescent nicotine exposure whose F0 generation parents also experienced adolescent nicotine exposure showed poorer learning of the violation element than rats that experienced adolescent nicotine exposure only in the F1 generation. Thus, adolescent nicotine exposure in one generation of rats produced a cognitive impairment in the next generation. Copyright © 2016 Elsevier Inc. All rights reserved.

Parecoxib sodium in the treatment of postoperative pain after Lichtenstein tension-free mesh inguinal hernia repair.

PubMed

Kyriakidis, A V; Perysinakis, I; Alexandris, I; Athanasiou, K; Papadopoulos, Ch; Mpesikos, I

2011-02-01

This prospective, randomized, double-blind study compared the analgesic efficacy and safety of parecoxib sodium versus lornoxicam and diclofenac, after Lichtenstein tension-free mesh inguinal hernia repair. Patients were randomly assigned to receive parecoxib 80 mg daily i.v. (Group A), lornoxicam 16 mg daily i.v. (Group B) or diclofenac 150 mg daily i.m. (Group C). Rescue analgesia in all groups consisted of pethidine 25 mg i.m. Pain was measured with an analogue scale (pain intensity score). Patients treated with parecoxib 80 mg reported significantly lower summed pain intensity scores compared with lornoxicam and diclofenac-treated patients. Duration of analgesia was also significantly longer with parecoxib than with lornoxicam and diclofenac. Adverse events were significantly less common in the parecoxib and lornoxicam group, compared with diclofenac group. Multiple-day administration of parecoxib 40 mg twice daily is more effective than equivalent doses of lornoxicam and diclofenac, and generally better tolerated than diclofenac after Lichtenstein tension-free mesh inguinal hernia repair.

Dextromethorphan/quinidine: in pseudobulbar affect.

PubMed

Garnock-Jones, Karly P

2011-05-01

Pseudobulbar affect is characterized by uncontrollable, inappropriate laughing and/or crying that is either unrelated or out of proportion to the emotions felt by the patient and occurs in patients with neurological disorders, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis or traumatic brain injury. Dextromethorphan/quinidine is indicated in the US for the treatment of pseudobulbar affect. Dextromethorphan, when its metabolism is inhibited by the coadministration of quinidine, has been shown to have a positive effect on the symptoms of pseudobulbar affect. Dextromethorphan/quinidine 20 mg/10 mg twice daily was associated with a significantly greater decrease in the rate of pseudobulbar affect episodes per day (primary endpoint) than placebo in the 12-week, randomized, double-blind, placebo-controlled, multicentre STAR trial (Safety, Tolerability, And efficacy Results trial of AVP-923 in PBA [pseudobulbar affect]) involving patients with pseudobulbar affect and ALS or multiple sclerosis. Moreover, the mean change from baseline in Center for Neurologic Study-Lability Scale score at 12 weeks was significantly greater among recipients of dextromethorphan/quinidine 20 mg/10 mg twice daily than those receiving placebo. Dextromethorphan/quinidine 20 mg/10 mg twice daily was generally well tolerated. The drug has been shown to cause dosage-dependent corrected QT interval (QTc) prolongation; however, in the STAR trial, dextromethorphan/quinidine 20 mg/10 mg twice daily appeared to be well tolerated with regard to QTc prolongation.

Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.

PubMed

Kremenchutzky, Marcelo; O'Connor, Paul; Hohlfeld, Reinhard; Zhang-Auberson, Lixin; von Rosenstiel, Philipp; Meng, Xiangyi; Grinspan, Augusto; Hashmonay, Ron; Kappos, Ludwig

2014-05-01

Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis. This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history. Annualized relapse rate and safety profile of treatment with fingolimod 0.5mg, 1.25mg, or placebo once-daily for 24 months were analyzed in 1272 relapsing multiple sclerosis patients, by subgroups based on disease-modifying therapy history (treatment-naive; prior interferon-β or glatiramer acetate), reason for discontinuation of prior disease-modifying therapy (unsatisfactory therapeutic response or adverse events), and prior disease-modifying therapy duration. Both fingolimod doses significantly reduced annualized relapse rate in patients that received prior interferon-β or glatiramer acetate, discontinued prior disease-modifying therapy owing to unsatisfactory therapeutic effect, were treatment-naive, or had prior disease-modifying therapy duration of >1-3 years (P≤0.0301 for all comparisons vs placebo). Fingolimod 1.25mg resulted in greater reductions in annualized relapse rate in patients that discontinued prior disease-modifying therapy for adverse events or had prior disease-modifying therapy duration of ≤1 year or >3 years (P≤0.0194 vs placebo). Fingolimod demonstrated similar efficacy in relapsing multiple sclerosis patients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of low-dose versus higher-dose antenatal iron supplementation on child health outcomes at 36 months of age in Viet Nam: longitudinal follow-up of a cluster randomised controlled trial.

PubMed

Hanieh, Sarah; Ha, Tran T; Simpson, Julie A; Braat, Sabine; Thuy, Tran T; Tran, Thach D; King, Janet; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

2017-01-01

Intermittent iron-folic acid supplementation (IFA) is currently recommended for pregnant women in populations where anaemia prevalence among pregnant women is <20% or if daily iron is not acceptable. The effect of providing lower doses of antenatal elemental iron through intermittent regimes on longer-term health outcomes in childhood is unclear. A prospective cohort study conducted between May 2012 and May 2014 in Viet Nam among children of 36 months of age, born to women previously enrolled in a cluster randomised controlled trial of antenatal micronutrient supplementation (daily IFA (60 mg elemental iron) vs twice-weekly IFA (60 mg elemental iron) vs twice-weekly multiple micronutrient (MMN) supplementation (60 mg elemental iron)). Primary outcomes were height-for-age z-scores (HAZ), according to WHO growth standards and cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) at 36 months of age. A total of 1017 children born to mothers enrolled in the cluster randomised trial were assessed at 36 months of age. Adjusted mean differences (MDs) in HAZ were -0.14 (95% CI -0.28 to -0.01) and -0.15 (95% CI -0.29 to -0.01) in children born to mothers who received twice-weekly IFA or MMN compared with those who received daily IFA. Children born to mothers who received twice-weekly MMN had lower composite motor scores compared with those who received daily IFA (MD -2.07, 95% CI -4.11 to -0.03). There were no differences in composite cognitive scores in the twice-weekly compared with daily regimens. Low-dose antenatal IFA supplementation (120 mg elemental iron per week) resulted in lower HAZ and motor composite scores in children compared with higher-dose antenatal IFA supplementation (420 mg elemental iron per week). This highlights the importance of adequate iron stores during pregnancy and the need for careful monitoring when lower-dose antenatal iron regimens are used. Australia New Zealand Clinical Trials Registry: 12610000944033.

BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma.

PubMed

Rossi, Adriana; Mark, Tomer; Jayabalan, David; Christos, Paul; Zafar, Faiza; Pekle, Karen; Pearse, Roger; Chen-Kiang, Selina; Coleman, Morton; Niesvizky, Ruben

2013-03-14

The combination of clarithromycin, lenalidomide, and dexamethasone (BiRd) was evaluated as therapy for treatment-naive symptomatic multiple myeloma (MM), with overall response at 2 years of 90%. We reviewed the long-term follow-up of initial BiRd therapy. Seventy-two patients were given dexamethasone 40 mg weekly, clarithromycin 500 mg twice daily, and lenalidomide 25 mg daily on days 1 to 21 of a 28-day cycle. After a median follow-up of 6.6 years, overall response rates were 93%, with a very good partial response or better of 68%. Median progression-free survival was 49 months. Evaluation for the development of second primary malignancies (SPMs) was conducted, and no increase in incidence was noted in our cohort of patients who received frontline immunomodulatory therapy. BiRd remains a highly potent and safe regimen for frontline therapy in patients with MM without apparent increase in risk of SPMs. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma

PubMed Central

Rossi, Adriana; Mark, Tomer; Jayabalan, David; Christos, Paul; Zafar, Faiza; Pekle, Karen; Pearse, Roger; Chen-Kiang, Selina; Coleman, Morton

2013-01-01

The combination of clarithromycin, lenalidomide, and dexamethasone (BiRd) was evaluated as therapy for treatment-naive symptomatic multiple myeloma (MM), with overall response at 2 years of 90%. We reviewed the long-term follow-up of initial BiRd therapy. Seventy-two patients were given dexamethasone 40 mg weekly, clarithromycin 500 mg twice daily, and lenalidomide 25 mg daily on days 1 to 21 of a 28-day cycle. After a median follow-up of 6.6 years, overall response rates were 93%, with a very good partial response or better of 68%. Median progression-free survival was 49 months. Evaluation for the development of second primary malignancies (SPMs) was conducted, and no increase in incidence was noted in our cohort of patients who received frontline immunomodulatory therapy. BiRd remains a highly potent and safe regimen for frontline therapy in patients with MM without apparent increase in risk of SPMs. This trial was registered at www.clinicaltrials.gov as #NCT00151203. PMID:23299315

Hypnosis as an adjunct therapy for asthma: case report.

PubMed

Neinstein, L S; Dash, J

1982-08-01

This study reports the effect of hypnotherapy in an asthmatic. The patient had moderately severe asthma with frequent attacks despite multiple medications. He received four weekly hypnosis sessions, and was then followed bimonthly for a year. The patient's course was followed by subjective daily scoring of wheezing severity, daily recording of peak expiratory flow rate by a Wright minispirometer, and once a month recording of his Forced Vital Capacity (FVC), Forced Expiratory Volume in one second/Forced Rate (MMRF). The severity rating showed improvement at one year when the start of therapy was compared to pretherapy (P less than .005). The daily peak flow rate averaged 486 liter/min before starting hypnotherapy and 502 liter/min after one year. There was no charge in the FEV1/FVC and MMFR before and after therapy. School attendance and academic performance may be a helpful adjunct in asthma therapy during adolescence.

Effects of frequent hemodialysis on perceived caregiver burden in the Frequent Hemodialysis Network trials.

PubMed

Suri, Rita S; Larive, Brett; Hall, Yoshio; Kimmel, Paul L; Kliger, Alan S; Levin, Nathan; Tamura, Manjula Kurella; Chertow, Glenn M

2014-05-01

Patients receiving hemodialysis often perceive their caregivers are overburdened. We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers. In two separate trials, 245 patients were randomized to receive in-center daily hemodialysis (6 days/week) or conventional hemodialysis (3 days/week) while 87 patients were randomized to receive home nocturnal hemodialysis (6 nights/week) or home conventional hemodialysis for 12 months. Changes in overall mean scores over time in the 10-question Cousineau perceived burden scale were compared. In total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline or during follow-up. Relative to in-center conventional dialysis, the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional dialysis, the 12-month change in mean perceived burden score with home nocturnal dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After multiple imputation for missing data in the Nocturnal Trial, the relative difference between home nocturnal and home conventional hemodialysis was +9.4 (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial, changes in perceived burden were inversely correlated with adherence to dialysis treatments (Pearson r=-0.35; P=0.02). Relative to conventional hemodialysis, in-center daily hemodialysis did not result in higher perceptions of caregiver burden. There was a trend to higher perceived caregiver burden among patients randomized to home nocturnal hemodialysis. These findings may have implications for the adoption of and adherence to frequent nocturnal hemodialysis.

Efficacy of multiple micronutrient supplementation for improving anemia, micronutrient status, growth, and morbidity of Peruvian infants.

PubMed

López de Romaña, Guillermo; Cusirramos, Sandra; López de Romaña, Daniel; Gross, Rainer

2005-03-01

Anemia, micronutrient deficiencies, and growth faltering are still common in Peru. The study objective was to determine the efficacy of different micronutrient supplements in preventing growth failure, anemia, and micronutrient deficiencies in Peruvian infants. Three hundred and thirteen infants aged 6 to 12 mo participated in a double-blind, masked, controlled trial in which they were randomly assigned to receive either a daily dose of iron (DI), a daily dose of multiple micronutrients (DMM), a weekly dose of multiple micronutrients, or a placebo (P) for 6 mo. None of the supplements tested prevented growth faltering or the morbidities common during infancy. Anemia and plasma homocysteine concentrations fell significantly in all groups during the study, but the mean change of plasma homocysteine during the trial period was significantly smaller in the DI group than in other groups, and the increase in hemoglobin concentrations was smaller in the P group than the micronutrient treatment groups. Plasma ferritin concentrations decreased least in the groups taking daily micronutrient supplements containing iron (DI and DMM). There were no significant differences among groups in mean final values or changes in plasma zinc, retinol, tocopherol, or riboflavin. Although the DMM intervention was the most efficacious for preventing anemia, iron, and zinc deficiencies, 15%, 20%, and 50% of this group still remained anemic, zinc deficient, and iron deficient, respectively, at the end of the study. Further research thus should investigate whether higher doses of iron and zinc, together with infection control measures, are more efficacious.

Salicylate-induced enzymuria: comparison with other anti-inflammatory agents.

PubMed

Proctor, R A; Kunin, C M

1978-12-01

N-acetyl-beta glucosaminidase (NAG) enzymuria was used as a marker of renal injury in patients with rheumatic disease. An elevated NAG level was particularly common in patients receiving gold or aspirin therapy. The multiplicity of drugs received and the unknown role of underlying disease in these patients led to a study in healthy volunteers. Customary therapeutic doses of aspirin, choline salicylate, ibuprofen, indomethacin and acetaminophen did not produce enzymuria. Large single doses of salicylates equivalent to 6 tablets of aspirin consistently did produce enzymuria. The size of the individual dose in relation to body weight was more important than the total daily dose. NAG enzymuria appears to be a sensitive tool for identifying potentially nephrotoxic drugs.

Intrathecal Baclofen Dosing Regimens: A Retrospective Chart Review.

PubMed

Clearfield, Jacob S; Nelson, Mary Elizabeth S; McGuire, John; Rein, Lisa E; Tarima, Sergey

2016-08-01

To examine dosing patterns in patients receiving baclofen via intrathecal baclofen pumps to assess for common patterns by diagnosis, ambulation ability, and affected limbs distribution. This trial study included 25 patients with baclofen pumps selected from the 356 patients enrolled in our center's baclofen pump program. Selection was done by splitting all patients into diagnostic categories of stroke, multiple sclerosis, traumatic/anoxic brain injury, cerebral palsy, and spinal cord injury, and then, five patients were randomly selected from each diagnosis.A systematic chart review was then conducted for each patient from Jan 1, 2008, through September 16, 2013, to look at factors including mean daily dose at end of study, and among those implanted during the study mean initial stable dose and time to initial stable dose. Analysis of mean daily dose across diagnoses found significant differences, with brain injury, cerebral palsy, and spinal cord injury patients having higher doses while multiple sclerosis and stroke patients required lower doses. Nonambulatory patients strongly trended to have higher daily doses than ambulatory patients. Similar trends of mean initial stable dose being higher in a similar pattern as that of end mean daily dose were seen according to diagnoses and ambulatory status, although statistical significance could not be achieved with the small sample size. Significant differences in dosing were found between diagnoses and trended to differ by ambulatory status at the end of the study, and similar trends could be observed in achieving initial stable dose. © 2015 International Neuromodulation Society.

Plants remember past weather: a study for atmospheric pollen concentrations of Ambrosia, Poaceae and Populus

NASA Astrophysics Data System (ADS)

Matyasovszky, István; Makra, László; Csépe, Zoltán; Sümeghy, Zoltán; Deák, Áron József; Pál-Molnár, Elemér; Tusnády, Gábor

2015-10-01

After extreme dry (wet) summers or years, pollen production of different taxa may decrease (increase) substantially. Accordingly, studying effects of current and past meteorological conditions on current pollen concentrations for different taxa have of major importance. The purpose of this study is separating the weight of current and past weather conditions influencing current pollen productions of three taxa. Two procedures, namely multiple correlations and factor analysis with special transformation are used. The 11-year (1997-2007) data sets include daily pollen counts of Ambrosia (ragweed), Poaceae (grasses) and Populus (poplar), as well as daily values of four climate variables (temperature, relative humidity, global solar flux and precipitation). Multiple correlations of daily pollen counts with simultaneous values of daily meteorological variables do not show annual course for Ambrosia, but do show definite trends for Populus and Poaceae. Results received using the two methods revealed characteristic similarities. For all the three taxa, the continental rainfall peak and additional local showers in the growing season can strengthen the weight of the current meteorological elements. However, due to the precipitation, big amount of water can be stored in the soil contributing to the effect of the past climate elements during dry periods. Higher climate sensitivity (especially water sensitivity) of the herbaceous taxa ( Ambrosia and Poaceae) can be definitely established compared to the arboreal Populus. Separation of the weight of the current and past weather conditions for different taxa involves practical importance both for health care and agricultural production.

Inverse Relationship between Coffee Consumption and Cerebral Microbleeds in Men, but Not Women.

PubMed

Shinoda, Masaki; Fujii, Motoharu; Takahashi, Osamu; Kawatsu, Akiko; Uemura, Akihiro; Niimi, Yasunari

2015-10-01

Studies evaluating the association between coffee consumption and neurovascular diseases have frequently yielded contradictory results. The aim of this study was to investigate the association of coffee consumption with small-vessel disease (SVD) incidence in a healthy urban population while accounting for multiple demographic and lifestyle risk factors. This prospective study conducted from May 2013 through March 2014 included 455 participants (314 men and 141 women) aged 25 to 92 years. All subjects completed a questionnaire on coffee consumption and received a comprehensive neurologic examination, including magnetic resonance imaging, at St. Luke's International Hospital (Tokyo, Japan). Incidence of SVD was lower in male daily coffee drinkers than male nondrinkers and occasional drinkers, whereas incidence of white matter lesions was lower in female daily coffee drinkers than female nondrinkers or occasional drinkers. In multivariate analyses including age, sex, smoking status, and BMI, as well as coffee consumption, incidence of microbleeds was significantly lower in male daily coffee drinkers compared to nondrinkers. Daily coffee consumption is associated with reduced risk of cerebral microbleeds in men. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Topical administration of regorafenib eye drops: phase I dose‐escalation study in healthy volunteers

PubMed Central

Höchel, Joachim; Becka, Michael; Boettger, Michael K.; Rohde, Beate; Schug, Barbara; Kunert, Kathleen S.; Donath, Frank

2018-01-01

Aim Regorafenib is a multikinase inhibitor under investigation for use in neovascular age‐related macular degeneration. In this phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure. Methods This was a single‐centre, randomized, double‐masked, parallel‐group, dose‐escalation, placebo‐controlled study. Subjects received regorafenib eye drops (30 mg ml−1, 25 μl) as a 0.75 mg single dose (Cohort 1), 0.75 mg twice daily (bid) or thrice daily (tid) over 14 days (Cohorts 2 and 3, respectively), 1.5 mg tid unilaterally for 3 days, then bilaterally for up to 14 days (Cohort 4), or placebo. Plasma samples were taken to estimate systemic exposure. Safety and functional assessments were performed throughout the study. Results Thirty‐six subjects received regorafenib and 12 received placebo. Regorafenib was safe and well tolerated over the dose range. No pathological changes occurred in the anterior, vitreous or posterior eye compartments. Mild eyelid redness, oedema and conjunctival hyperaemia were observed across all regorafenib cohorts; these were comparable with the effects seen with placebo. Predominant symptoms were blurred vision in the active and placebo groups. Systemic safety evaluations showed no clinically relevant findings. Absolute systemic exposure after multiple administrations of regorafenib eye drops at a dose of 0.75 mg was 600–700‐fold lower than after multiple oral administration of 160 mg day−1, the dose approved in cancer indications. Conclusion These results indicate a favourable safety and tolerability profile of regorafenib eye drops up to 30 mg ml−1 tid for use in clinical studies. PMID:29315699

Correction of anemia in a transfusion-dependent patient with primary myelofibrosis receiving iron chelation therapy with deferasirox (Exjade®, ICL670)

PubMed Central

Di Tucci, Anna Angela; Murru, Roberta; Alberti, Daniele; Rabault, Bertrand; Deplano, Simona; Angelucci, Emanuele

2007-01-01

Transfusional iron overload in patients with chronic anemias can result in multiple organ failure. Experience in the management of iron overload in patients with myelodysplastic syndromes is limited, as many do not receive chelation therapy due to short-life expectancy and the difficulties associated with the administration of the current reference standard chelator, deferoxamine. There have, however, been some reports of reduced transfusion requirement associated with chelation therapy in patients with myelodysplastic syndromes and myelofibrosis. Here, we discuss a patient with primary myelofibrosis and related transfusion-dependent anemia who received chelation therapy with the once-daily oral iron chelator, deferasirox. In addition to the reduced iron levels, the patient demonstrated an unexpected reduction in blood transfusion requirement, ultimately resulting in long-lasting transfusion-free survival. PMID:17391307

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

PubMed

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or 150 IU once daily [QD], or 150 IU every other day [QAD], 10 subjects each) and 27 subjects received 150 IU Gonal-f, 150 IU Bravelle, or placebo for 7 days (11/10/6 subjects). Blood samples for measuring PK as well as PD parameters were collected systematically before, during and after dosing. Adverse events (AEs) and other relevant safety parameters were recorded. Data were summarized using descriptive statistics. The single- and multiple-dose PK parameters maximum concentration (Cmax) and area under the concentration-time curve (AUC0-last) increased in a linear fashion with increasing dose levels of follitropin epsilon. Follitropin epsilon showed PK characteristics comparable to the comparators indicating that well established treatment schemes could be applied. There was a dose-response effect of single and multiple doses of follitropin epsilon on follicular growth, which was shown for the biomarker inhibin B as well as for the mean number and size of follicles. Multiple doses of 75 IU follitropin epsilon given daily, as well as 150 IU follitropin epsilon every second day, showed a follicle growth comparable with 150 IU Gonal-f given daily, while in case of daily administration of 150 IU Bravelle only weak follicle stimulation was observed. Multiple doses of 150 IU follitropin epsilon induced a much higher follicle growth compared to the same dose of Gonal-f. All single and multiple follitropin epsilon doses tested were safe and well tolerated, and overall there were no relevant differences between follitropin epsilon and the comparators in terms of safety. The average number of AEs increased with increasing dose levels. No clinically relevant abnormalities were reported for any of the other safety parameters assessed. No follitropin epsilon anti-drug antibodies were observed. The studies were conducted as a single-blind design. Hormone levels or other parameters assessed in serum are generally not considered as being subject to bias. Other assessments directly performed by the investigators, such as transvaginal ultrasound assessments, may have been subject to personal bias. No prospective calculations of statistical power had been made, as is common practice for first in human and early phase I studies in healthy volunteers. These early development studies showed that follitropin epsilon exhibits comparable PK characteristics, as well as inducing stronger PD effects in terms of follicle growth and serum inhibin B, than the comparators. Follitropin epsilon induced a dose-dependent increase in follicular growth. The results warrant further studies with this new fully human recombinant FSH. The studies were sponsored by GLYCOTOPE GmbH, Berlin, Germany. K.A-E. is an employee of QPS-Netherlands, B.V., which received funding for the studies from Glycotope GmbH; I.D. and C.K. are employees of Dinox B.V., which received funding for the studies from Glycotope GmbH; L.S. and S.G. are employees and shareholders of Glycotope GmbH; B.D. and K.E. are employees of Glycotope GmbH. www.clinicaltrials.gov: NCT01354886 (single-dose); NCT01477073 (multiple-dose). The single-dose trial was registered on 11 May 2011 while the multiple-dose trial was registered on 09 November 2011. First subject was enroled in the single-dose trial in 27 April 2011 and in the multiple-dose trial in 02 October 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Novel therapy in multiple myeloma.

PubMed

Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Cleto, Sergio; Castañeda, Claudia; González, Martha; Talavera, Alejandra; Huerta-Guzmán, Judith

2005-10-01

Treatment in patients with multiple myeloma remain to be defined. Younger patients (defined as a cut-off level < 65 years old) will be treated with chemotherapy and transplant procedures. However, most patients > 65 years old are not candidates for this therapeutic approach and the use of intensive chemotherapy could be associated to severe toxicity. We developed an new, not-cytotoxic regimen with dexamethasone 30 mg/m(2), iv, days 1 to 4, all trans retinoic acid 45 mg/m(2), po, days 5 to 14 and interferon alfa 2a 4.5 MU, sc, daily, days 5 to 14 (DAI regimen) administered every 28 days in number of 6 cycles, at this point patients were restaging, if they showed complete response, objective response or partial response they were conducted to received thalidomide 100-200 mg po, daily and dexamethasone 10 mg/2, po days 1 to 4 at monthly intervals, for 18 months. Forty one patients were enrolled in an Phase II study. In an intent to treat analysis all patients were evaluable. Complete response was observed in 18 cases (43%), objective response in 10 patients (24%) and partial response in 5 patients (12%), overall response rate was 80%. Eight patients were considered failures. At an median of 36 months, no relapse of progression disease has been observed, thus actuarial curves at 3-years showed that event free survival is 100% and overall survival is 91%. Toxicity was mild, all patients received the planned dose in time. This regimen appear to be useful in older patients with multiple myeloma, the response rate is higher and toxicity was mild. Controlled clinical trials comparing with conventional chemotherapy will be conducted to define the role of this therapeutic approach.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.

PubMed

Rapoport, Bernardo; Schwartzberg, Lee; Chasen, Martin; Powers, Dan; Arora, Sujata; Navari, Rudolph; Schnadig, Ian

2016-04-01

Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021). Over cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p < 0.001). The incidence of treatment-related adverse events during cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma.

PubMed

Mark, Tomer M; Bowman, Isaac A; Rossi, Adriana C; Shah, Manan; Rodriguez, Melissa; Quinn, Ryann; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Jayabalan, David; Ely, Scott; Coleman, Morton; Chen-Kiang, Selina; Niesvizky, Ruben

2014-12-01

We studied T-BiRD (thalidomide [Thalomid(®)], clarithromycin [Biaxin(®)], lenalidomide [Revlimid(®)] and dexamethasone) in symptomatic, newly diagnosed multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide 25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11 patients who underwent autologous stem cell transplantation as part of first-line therapy. The 4-year overall survival rate was 74.9%, and the median progression-free survival was 35.6 months. Eight patients discontinued due to regimen toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD is a highly active regimen with potential toxicity limitations. ClinicalTrials.gov identifier: NCT00538733.

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.

PubMed

Karschner, Erin L; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deanna L; Gorelick, David A; Huestis, Marilyn A

2012-10-01

Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively. Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. Published by Elsevier Ireland Ltd.

Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk of falling in ambulatory women aged 65-71 years? A 3-year randomized population-based trial (OSTPRE-FPS).

PubMed

Kärkkäinen, Matti K; Tuppurainen, Marjo; Salovaara, Kari; Sandini, Lorenzo; Rikkonen, Toni; Sirola, Joonas; Honkanen, Risto; Arokoski, Jari; Alhava, Esko; Kröger, Heikki

2010-04-01

The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level. The OSTPRE-FPS was a randomized population-based open-trial with 3-year follow-up. The supplementation group (n=1566) received daily cholecalciferol 800IU+calcium carbonate 1000mg, while the control group (n=1573) received no supplementation or placebo. A randomly selected subsample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements. The occurrence of falls was the primary outcome of the study. The participants in the subsample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year. In the entire trial population (ETP), there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group (risk ratio was 0.98, 95% CI 0.92-1.05, P=0.160). The supplementation was not associated with single or multiple falls in the ETP. However, in the subsample, multiple fall incidence decreased by 30% (odds ratio (OR) 0.70, 95% CI 0.50-0.97, P=0.034) in the supplementation group. Further, the supplementation decreased the incidence of multiple falls requiring medical attention (OR 0.72, 95% CI 0.53-0.97, P=0.031) in the ETP. The mean compliance in the entire trial population was 78% and in the subsample 79%. Overall, the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls. However, the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention: this finding requires confirmation. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

PubMed

Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

2015-01-01

Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily dosing. Doravirine at steady state slightly reduced the exposure of coadministered midazolam, to a clinically unimportant extent.

First-in-human testing of a wirelessly controlled drug delivery microchip.

PubMed

Farra, Robert; Sheppard, Norman F; McCabe, Laura; Neer, Robert M; Anderson, James M; Santini, John T; Cima, Michael J; Langer, Robert

2012-02-22

The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1-34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1-34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1-34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1-34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.

Habitat selection by green turtles in a spatially heterogeneous benthic landscape in Dry Tortugas National Park, Florida

USGS Publications Warehouse

Fujisaki, Ikuko; Hart, Kristen M.; Sartain-Iverson, Autumn R.

2016-01-01

We examined habitat selection by green turtles Chelonia mydas at Dry Tortugas National Park, Florida, USA. We tracked 15 turtles (6 females and 9 males) using platform transmitter terminals (PTTs); 13 of these turtles were equipped with additional acoustic transmitters. Location data by PTTs comprised periods of 40 to 226 d in varying months from 2009 to 2012. Core areas were concentrated in shallow water (mean bathymetry depth of 7.7 m) with a comparably dense coverage of seagrass; however, the utilization distribution overlap index indicated a low degree of habitat sharing. The probability of detecting a turtle on an acoustic receiver was inversely associated with the distance from the receiver to turtle capture sites and was lower in shallower water. The estimated daily detection probability of a single turtle at a given acoustic station throughout the acoustic array was small (<0.1 in any year), and that of multiple turtle detections was even smaller. However, the conditional probability of multiple turtle detections, given at least one turtle detection at a receiver, was much higher despite the small number of tagged turtles in each year (n = 1 to 5). Also, multiple detections of different turtles at a receiver frequently occurred within a few minutes (40%, or 164 of 415, occurred within 1 min). Our numerical estimates of core area overlap, co-occupancy probabilities, and habitat characterization for green turtles could be used to guide conservation of the area to sustain the population of this species.

The Effect of Combining Business Training, Microfinance, and Support Group Participation on Economic Status and Intimate Partner Violence in an Unplanned Settlement of Nairobi, Kenya.

PubMed

Sarnquist, Clea C; Ouma, Linda; Lang'at, Nickson; Lubanga, Chrisanthus; Sinclair, Jake; Baiocchi, Michael T; Cornfield, David N

2018-06-01

Intimate partner violence (IPV) has myriad negative health and economic consequences for women and families. We hypothesized that empowering women through a combination of formal business training, microfinance, and IPV support groups would decrease IPV and improve women's economic status. The study included adult female survivors of severe IPV. Women living in Korogocho received the intervention and women in Dandora served as a standard of care (SOC) group, but received the intervention at the end of the follow-up period. Women in the intervention groups ( n = 82, SOC group, n = 81) received 8 weeks of business training, assistance creating a business plan, a small initial loan (about US$60), and weekly business and social support meetings. The two primary outcome measures included change in: (a) average daily profit margin, and (b) incidence of severe IPV. Exploratory analysis also looked at incidence of violence against children and women's self-efficacy. Average daily profit margin in the intervention group increased by 351 Kenyan Shillings (about US$3.5) daily (95% CI = [172, 485]). IPV directed against participating women decreased from a baseline of 2.1 to 0.26 incidents, a difference of 1.84 incidents (95% CI = [1.32, 2.36]). Violence against children in the household in the prior 3 months decreased from 1.1 to 0.55 incidents, a difference of 0.55 incidents (95% CI = [0.16, 1.03]). Finally, the intervention appears to have increased self-efficacy scores by 0.42 points (95% CIs 0.13, 0.71). In a low-resource urban environment, employing three complementary interventions resulted in higher daily profit margins and lower IPV in the intervention compared with the SOC group. These data support the notion that employing multiple interventions concomitantly might possess synergistic, beneficial effects, and hold promise to address profound poverty and interrupt the devastating cycle of IPV.

Continuous Glucose Monitoring vs Conventional Therapy for Glycemic Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections: The GOLD Randomized Clinical Trial.

PubMed

Lind, Marcus; Polonsky, William; Hirsch, Irl B; Heise, Tim; Bolinder, Jan; Dahlqvist, Sofia; Schwarz, Erik; Ólafsdóttir, Arndís Finna; Frid, Anders; Wedel, Hans; Ahlén, Elsa; Nyström, Thomas; Hellman, Jarl

2017-01-24

The majority of individuals with type 1 diabetes do not meet recommended glycemic targets. To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections. Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5% (58 mmol/mol) treated with multiple daily insulin injections. Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks. Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied. Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA1c was 8.6% (70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92% (63 mmol/mol) during continuous glucose monitoring use and 8.35% (68 mmol/mol) during conventional treatment (mean difference, -0.43% [95% CI, -0.57% to -0.29%] or -4.7 [-6.3 to -3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia. Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Further research is needed to assess clinical outcomes and longer-term adverse effects. clinicaltrials.gov Identifier: NCT02092051.

A Combined Intervention of Zinc, Multiple Micronutrients, and Albendazole Does Not Ameliorate Environmental Enteric Dysfunction or Stunting in Rural Malawian Children in a Double-Blind Randomized Controlled Trial.

PubMed

Wang, Alfred Z; Shulman, Robert J; Crocker, Audrey H; Thakwalakwa, Chrissie; Maleta, Kenneth M; Devaraj, Sridevi; Manary, Mark J; Trehan, Indi

2017-01-01

Environmental enteric dysfunction (EED) and linear growth stunting affect many rural agrarian children in the developing world and contribute to the persistently high rates of stunting that are observed worldwide. Effective interventions to consistently ameliorate EED are lacking. We tested whether a bundle of safe and affordable interventions would decrease EED and stunting over 12-24 wk in a cohort of rural Malawian children 12-35 mo old. This was a randomized, double-blind, placebo-controlled clinical trial in which the intervention group received a single dose of albendazole and 14 d of zinc at enrollment and after 20 wk. The intervention group also received a daily multiple micronutrient powder throughout the 24 wk of study. The primary outcomes were improvements in EED, as measured by the urinary lactulose-to-mannitol ratio (L:M ratio) from dual-sugar absorption testing, and linear growth. Urinary L:M ratios and anthropometric measurements were evaluated after 12 and 24 wk of intervention and compared with a placebo group that did not receive any of these interventions. A total of 254 children were enrolled at a mean age of 24 mo; 55% were female. Their mean weight-for-age z score was -1.5, and their mean length-for-age z score was -0.9. After 12 and 24 wk of study, increases in the L:M ratio did not differ between the intervention group (0.071 and 0.088 units, respectively) and the placebo group (0.073 and 0.080 units, respectively) (P = 0.87 and 0.19, respectively). Relative changes in length and weight also did not differ significantly between groups at any time point. The combined usage of albendazole, zinc, and a daily multiple micronutrient powder did not decrease EED or stunting in this population of agrarian children 12-35 mo old in rural Malawi. Alternative interventions to improve these diseases should be investigated. This trial was registered at clinicaltrials.gov as NCT02253095. © 2017 American Society for Nutrition.

Behavioral and neurochemical consequences of multiple MDMA administrations in the rat: role of individual differences in anxiety-related behavior.

PubMed

Ludwig, V; Mihov, Y; Schwarting, R K W

2008-05-16

Using the elevated plus-maze (EPM), Wistar rats can be distinguished into high (HA) or low anxiety (LA) subjects. These differences seem to reflect traits, since HA and LA rats vary also in other anxiety-dependent tasks, neurochemical mechanisms, and psychopharmacological reactivity, including lasting consequences after single treatment with 3,4-methylenedioxymethamphetamine (MDMA). Here, we tested whether multiple MDMA treatments also have subject-dependent effects. Based on routine EPM screening, male Wistar rats were divided into HA and LA sub-groups, which received five (i.e. multiple) daily injections of MDMA (5 mg/kg) or saline, followed by a test battery, including a challenge test with MDMA, a retest in the EPM, a novel-object test, and a final neurochemical analysis. Acutely, MDMA led to comparable hyperactivity in HA and LA rats. After multiple MDMA, behavioral sensitization was observed, especially in LA rats. Open arm time during the EPM retest (min 0-5) correlated with that of the initial one only in those rats, which had received a single injection of MDMA. Rats with multiple MDMA, especially LA-rats, showed more open-arm time and locomotion during the subsequent 5-10 min of the retest. In a novel-object test, rats with multiple MDMA, again especially LA subjects, showed more exploratory bouts towards the novel object. Neurochemically, multiple MDMA led to moderately lower serotonin in the ventral striatum, and higher dopamine levels in the frontal cortex as compared to single MDMA; these effects were also moderated by subject-dependent factors. Our data show that low-dosed multiple MDMA can lead to behavioral sensitization and outlasting consequences, which affect behavior in the EPM and a novel object task. Detecting such sequels partly requires consideration of individual differences.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buckley, L; Lambert, C; Nyiri, B

Purpose: To standardize the tube calibration for Elekta XVI cone beam CT (CBCT) systems in order to provide a meaningful estimate of the daily imaging dose and reduce the variation between units in a large centre with multiple treatment units. Methods: Initial measurements of the output from the CBCT systems were made using a Farmer chamber and standard CTDI phantom. The correlation between the measured CTDI and the tube current was confirmed using an Unfors Xi detector which was then used to perform a tube current calibration on each unit. Results: Initial measurements showed measured tube current variations of upmore » to 25% between units for scans with the same image settings. In order to reasonably estimate the imaging dose, a systematic approach to x-ray generator calibration was adopted to ensure that the imaging dose was consistent across all units at the centre and was adopted as part of the routine quality assurance program. Subsequent measurements show that the variation in measured dose across nine units is on the order of 5%. Conclusion: Increasingly, patients receiving radiation therapy have extended life expectancies and therefore the cumulative dose from daily imaging should not be ignored. In theory, an estimate of imaging dose can be made from the imaging parameters. However, measurements have shown that there are large differences in the x-ray generator calibration as installed at the clinic. Current protocols recommend routine checks of dose to ensure constancy. The present study suggests that in addition to constancy checks on a single machine, a tube current calibration should be performed on every unit to ensure agreement across multiple machines. This is crucial at a large centre with multiple units in order to provide physicians with a meaningful estimate of the daily imaging dose.« less

A HIERARCHIAL STOCHASTIC MODEL OF LARGE SCALE ATMOSPHERIC CIRCULATION PATTERNS AND MULTIPLE STATION DAILY PRECIPITATION

EPA Science Inventory

A stochastic model of weather states and concurrent daily precipitation at multiple precipitation stations is described. our algorithms are invested for classification of daily weather states; k means, fuzzy clustering, principal components, and principal components coupled with ...

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

PubMed

Richardson, Paul G; Bensinger, William I; Huff, Carol Ann; Costello, Caitlin L; Lendvai, Nikoletta; Berdeja, Jesus G; Anderson, Larry D; Siegel, David S; Lebovic, Daniel; Jagannath, Sundar; Laubach, Jacob P; Stockerl-Goldstein, Keith E; Kwei, Long; Clow, Fong; Elias, Laurence; Salman, Zeena; Graef, Thorsten; Bilotti, Elizabeth; Vij, Ravi

2018-03-01

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0-14·7). Progression-free survival was 4·6 months (range, 0·4-17·3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

PubMed

Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

2017-09-01

Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Impact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics.

PubMed

Freise, Kevin J; Hu, Beibei; Salem, Ahmed Hamed

2018-04-01

Venetoclax is a selective BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). It is predominately metabolized by cytochrome P450 (CYP) 3A. The study objective was to determine the effect of different dosage regimens of ritonavir, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax in 20 healthy subjects. In cohorts 1 and 2, subjects received single 10 mg doses of venetoclax in periods 1 and 2 and a single 50- or 100-mg dose of ritonavir in period 2. In cohort 3, subjects received 10-mg venetoclax doses on day 1 of period 1 and days 1 and 11 of period 2, and 50 mg ritonavir daily on days 1 to 14 of period 2. Single doses of 50 and 100 mg ritonavir increased the venetoclax maximum concentration (C max ) 2.3- to 2.4-fold compared to venetoclax alone and the area under the curve (AUC) 6.1- and 8.1-fold, respectively. Daily 50 mg ritonavir resulted in a 2.4- and 7.9-fold increase in venetoclax C max and AUC, respectively. Administration of 50 mg ritonavir daily saturated CYP3A inhibition and completely inhibited the formation of the major venetoclax metabolite M27. Time-dependent CYP3A inhibition with daily 50 mg ritonavir was offset by ritonavir CYP3A induction, resulting in a limited net increase in CYP3A inhibition with multiple doses. After completion of the dose ramp-up, venetoclax dose reductions of at least 75% are recommended when administered concomitantly with strong CYP3A inhibitors to maintain venetoclax exposures within the established therapeutic window for CLL treatment.

Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

PubMed Central

Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P.

2009-01-01

Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Objective: Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. Design: This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Participants: Fifty-five healthy, regularly cycling premenopausal women participated. Interventions: Subjects were administered a single oral dose of 25–400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (±1) after onset of menses. Main Outcome Measures: Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Results: Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50–200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 ± 3 to 68 ± 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Conclusions: Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states. PMID:19033369

Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix.

PubMed

Struthers, R Scott; Nicholls, Andrew J; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S C; Bozigian, Haig P

2009-02-01

Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Fifty-five healthy, regularly cycling premenopausal women participated. Subjects were administered a single oral dose of 25-400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (+/-1) after onset of menses. Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50-200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 +/- 3 to 68 +/- 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states.

Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

NASA Astrophysics Data System (ADS)

Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

2015-08-01

Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.

PubMed

Panitch, Hillel S; Thisted, Ronald A; Smith, Richard A; Wynn, Daniel R; Wymer, James P; Achiron, Anat; Vollmer, Timothy L; Mandler, Raul N; Dietrich, Dennis W; Fletcher, Malcolm; Pope, Laura E; Berg, James E; Miller, Ariel

2006-05-01

To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients. A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess pseudobulbar affect with the validated Center for Neurologic Study-Lability Scale. Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale. Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85). All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p

Timed instrumental activities of daily living in multiple sclerosis: The test of everyday cognitive ability (TECA).

PubMed

Charvet, Leigh E; Shaw, Michael T; Sherman, Kathleen; Haas, Shannon; Krupp, Lauren B

2018-05-03

Cognitive impairment is a common symptom of multiple sclerosis (MS) that can lead to declines in daily functioning. Timed instrumental activities of daily living (TIADLs) have been useful to bridge between cognitive testing and real-world functioning in disorders such as Alzheimer's disease and other dementias. However, these have not been standardized for general use, and the tasks that are typically employed have not been sensitive to the detection of milder forms of cognitive deficits. We developed a test of ten TIADLs tasks to measure a broader range of functioning, entitled the "Test of Everyday Cognitive Ability" or TECA, and tested its utility in a diverse sample of participants with MS. TECA performance was characterized in n = 177 participants with MS and compared to healthy controls (n = 49). A subset from each group received repeated administration. In addition, all participants completed a standard battery of neuropsychological measures. TECA performances were significantly different between MS and control participants. Further, MS participants with cognitive impairment performed significantly slower relative to those MS participants without impairment. The TECA is a TIADLs assessment appropriate for use in those with MS as it includes a broad range of task difficulties, requires minimum motor involvement, and is sensitive to MS-related cognitive impairment. The TECA is a brief and repeatable test of TIADLs and its ease of administration makes it suitable for both clinical practice and research settings. Copyright © 2018 Elsevier B.V. All rights reserved.

The Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE): study protocol for a cluster randomised controlled trial.

PubMed

White, David; Waugh, Norman; Elliott, Jackie; Lawton, Julia; Barnard, Katharine; Campbell, Michael J; Dixon, Simon; Heller, Simon

2014-09-03

People with type 1 diabetes (T1DM) require insulin therapy to sustain life, and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications. Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump (continuous subcutaneous insulin infusion), a more costly option with benefits for some patients. The UK National Institute for Health and Care Excellence (NICE) recommend the use of pumps for patients with the greatest need, citing insufficient evidence to approve extension to a wider population. Far fewer UK adults use pumps than in comparable countries. Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment. This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections, where both groups are provided with high-quality structured education. A multicentre, parallel group, cluster randomised controlled trial among 280 adults with T1DM. All participants attended the week-long dose adjustment for normal eating (DAFNE) structured education course, and receive either multiple daily injections or pump therapy for 2 years. The trial incorporates a detailed mixed-methods psychosocial evaluation and cost-effectiveness analysis. The primary outcome will be the change in glycosylated haemoglobin (HbA1c) at 24 months in those participants whose baseline HbA1c is at or above 7.5% (58 mmol/mol). The key secondary outcome will be the proportion of participants reaching the NICE target of an HbA1c of 7.5% (58 mmol/mol) or less at 24 months. The protocol was approved by the Research Ethics Committee North West, Liverpool East and received Medicines and Healthcare products Regulatory Agency (MHRA) clinical trials authorisation. Each participating centre gave National Health Service R&D approval. We shall disseminate study findings to study participants and through peer reviewed publications and conference presentations, including lay user groups. ISRCTN 61215213. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type 2 diabetes mellitus.

PubMed

Vajda, Eric G; Logan, Douglas; Lasseter, Kenneth; Armas, Danielle; Plotkin, Diane J; Pipkin, J D; Li, Yong-Xi; Zhou, Rong; Klein, David; Wei, Xiaoxiong; Dilzer, Stacy; Zhi, Lin; Marschke, Keith B

2017-01-01

To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of a novel, oral glucagon receptor antagonist, LGD-6972, in healthy subjects and subjects with type 2 diabetes (T2DM). In the single ascending dose study, LGD-6972 (2-480 mg) was administered to healthy subjects (n = 48) and T2DM subjects (n = 8). In the multiple ascending dose study, healthy subjects (n = 12) received a dose of 15 mg LGD-6972 and T2DM subjects (n = 36) received doses of 5, 10 or 15 mg of LGD-6972 daily for 14 days. LGD-6972 had linear plasma pharmacokinetics consistent with once-daily dosing that was comparable in healthy and T2DM subjects. Dose-dependent decreases in fasting plasma glucose were observed in all groups with a maximum of 3.15 mmol/L (56.8 mg/dL) on day 14 in T2DM subjects. LGD-6972 also reduced plasma glucose in the postprandial state. Dose-dependent increases in fasting plasma glucagon were observed, but glucagon levels decreased and insulin levels increased after an oral glucose load in T2DM subjects. LGD-6972 was well tolerated at the doses tested without dose-related or clinically meaningful changes in clinical laboratory parameters. No subject experienced hypoglycaemia. Inhibition of glucagon action by LGD-6972 was associated with decreases in glucose in both healthy and T2DM subjects, the magnitude of which was sufficient to predict improvement in glycaemic control with longer treatment duration in T2DM patients. The safety and pharmacological profile of LGD-6972 after 14 days of dosing supports continued clinical development. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC*

PubMed Central

Karschner, Erin L.; Schwope, David M.; Schwilke, Eugene W.; Goodwin, Robert S.; Kelly, Deanna L.; Gorelick, David A.; Huestis, Marilyn A.

2012-01-01

Background Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Methods Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Results Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5 h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5 h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5 h after the last THC dose, respectively. Conclusions Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. PMID:22464363

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study

PubMed Central

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-01-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. PMID:25533447

A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

PubMed

Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

1989-12-01

Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

Activities of daily living in nursing home and home care settings: a retrospective 1-year cohort study.

PubMed

Lee, Tae Wha; Cho, Eunhee; Yim, Eun Shil; Lee, Hye Sun; Ko, Yu Kyung; Kim, Bok Nam; Kim, Sinhye

2015-02-01

Korea introduced universal long-term care insurance (LTCI) for physically dependent older adults in 2008. Older adults, their family members, and policy makers in Korea want to know patient outcomes in different care modalities because older adults who have a similar functional status and LTC needs can choose either nursing home care or home care. The aim of this study was to compare activities of daily living (ADLs) in nursing home care and home care settings for physically dependent older adults in Korea. A retrospective 1-year cohort study using national LTCI data. This study used the LTCI dataset from the National Health Insurance Service in Korea. Participants were identified from among those in the LTCI dataset who enrolled from July 2008 to June 2010. We extracted a sample consisting of 22,557 older adults who consistently received either nursing home care (n = 11,678) or home care (n = 10,879) for 1 year. The outcome variable was change in ADLs after 1 year. Covariates were an older adult's home geographical region, LTC level, age, sex, primary caregiver, Medicaid beneficiary status, bedridden status, medical diagnosis, baseline ADLs, cognitive function, behavioral problems, nursing and special treatment, and rehabilitation needs. Multiple regression analysis of all participants unmatched and a paired t-test with a propensity-score-matched cohort were performed to explain the association of changes in ADLs with the types of LTC. Multiple regression analysis with all participants (n = 22,557) unmatched showed that compared with older adults who received home care, those who received nursing home care had deteriorated further in terms of ADLs after 1 year (β = 0.44108, P < .0001). After propensity-score matching, paired t-test analysis also found that the ADLs of older adults had deteriorated less in the home care group compared with the nursing home group after 1 year (P < .0001). The ADLs of older adults who received home care showed significantly less deterioration than those of the older adults in nursing home care after 1 year. The ADLs of older adults could differ according to the type of LTC they receive, and home care could result in better maintenance of ADLs than nursing home care. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.

PubMed

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-05-01

A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects. Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing. Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated. Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration. With increasing single and multiple doses of THC/CBD spray, the mean peak plasma concentration (Cmax) increased for all analytes. There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration (Tmax) was longest for all analytes in the eight spray group, but was similar in the two and four spray groups. THC/CBD spray was well-tolerated in this study and no serious adverse events were reported. The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity. There was also no evidence of accumulation on repeated dosing.

Impact of dental pain on daily living of five-year-old Brazilian preschool children: prevalence and associated factors.

PubMed

Moure-Leite, F R; Ramos-Jorge, J; Ramos-Jorge, M L; Paiva, S M; Vale, M P; Pordeus, I A

2011-12-01

To assess the impact of dental pain on the daily living of 5-year-old preschool children using reports from parents/guardians. A cross-sectional study was carried out involving 549 five-year-old children randomly selected from preschools in the city of Belo Horizonte, Brazil. Data were collected using a previously validated parent-reported questionnaire. The children received dental examinations from a single calibrated examiner. The following outcome variables were selected: age, gender, dental caries, filled teeth, missing teeth, caries involving pulp and social class. Simple and multiple logistic regression analyses were performed on the data. According to parents' reports, 11.1% of children were affected by dental pain in the previous 4 months and of these 72.6% had their daily activities hampered by pain. The majority of these children had difficulty in eating, brushing teeth, sleeping, playing and going to school. The impact of dental pain had a statistically significant association with gender (p=0.001), social class (p=0.009), dental caries (p<0.001), missing teeth (p<0.001), filled teeth (p<0.001) and caries involving pulp (p<0.001). The prevalence of difficulties performing tasks of daily living due to dental pain was relatively high among the children studied.

Determinants of complications after multiple transrectal core biopsies of the prostate.

PubMed

Norberg, M; Holmberg, L; Häggman, M; Magnusson, A

1996-01-01

Transrectal ultrasound-guided biopsies of the prostate were performed on 347 consecutive men. All patients were given prophylactic antibiotics. The first 199 patients received 400 mg norfloxacin immediately after the biopsies were performed and 400 mg the same evening. The second group of 148 patients received 400 mg of norfloxacin 1 h before the examination followed by five doses administered twice daily. A total of 15 major complications were noted. In the first group the complication rate was 6.5% and in the second group 1.4%. The different regimes of prophylactic antibiotic treatment were the only parameters shown to have a statistically significant impact on the complication rate. The number of complications decreased, but were not eliminated, when prophylactic treatment with norfloxacin was given before the biopsies were taken and continued for a total of 3 days.

Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial.

PubMed

Reznik, Yves; Cohen, Ohad; Aronson, Ronnie; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; Lee, Scott W

2014-10-04

Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise). We did this multicentre, controlled trial at 36 hospitals, tertiary care centres, and referal centres in Canada, Europe, Israel, South Africa, and the USA. Patients with type 2 diabetes who had poor glycaemic control despite multiple daily injections with insulin analogues were enrolled into a 2-month dose-optimisation run-in period. After the run-in period, patients with glycated haemoglobin of 8·0-12·0% (64-108 mmol/mol) were randomly assigned (1:1) by a computer-generated randomisation sequence (block size 2 with probability 0·75 and size 4 with probability 0·25) to pump treatment or to continue with multiple daily injections. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was change in mean glycated haemoglobin between baseline and end of the randomised phase for the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01182493. 495 of 590 screened patients entered the run-in phase and 331 were randomised (168 to pump treatment, 163 to multiple daily injections). Mean glycated haemoglobin at baseline was 9% (75 mmol/mol) in both groups. At 6 months, mean glycated haemoglobin had decreased by 1·1% (SD 1·2; 12 mmol/mol, SD 13) in the pump treatment group and 0·4% (SD 1·1; 4 mmol/mol, SD 12) in the multiple daily injection group, resulting in a between-group treatment difference of -0·7% (95% CI -0·9 to -0·4; -8 mmol/mol, 95% CI -10 to -4, p<0·0001). At the end of the study, the mean total daily insulin dose was 97 units (SD 56) with pump treatment versus 122 units (SD 68) for multiple daily injections (p<0·0001), with no significant difference in bodyweight change between the two groups (1·5 kg [SD 3·5] vs 1·1 kg [3·6], p=0·322). Two diabetes-related serious adverse events (hyperglycaemia or ketosis without acidosis) resulting in hospital admission occurred in the pump treatment group compared with one in the multiple daily injection group. No ketoacidosis occurred in either group and one episode of severe hypoglycaemia occurred in the multiple daily injection group. In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option. Medtronic. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of stress-induced diabetes on outcomes in severely burned children.

PubMed

Finnerty, Celeste C; Ali, Arham; McLean, Josef; Benjamin, Nicole; Clayton, Robert P; Andersen, Clark R; Mlcak, Ronald P; Suman, Oscar E; Meyer, Walter; Herndon, David N

2014-04-01

Post-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60 and 110 mg/dL. Because of frequent hypoglycemic episodes, a less-stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80 and 160 mg/dL after elevations >180 mg/dL. We randomized pediatric patients with massive burns into 2 groups, patients receiving sliding scale insulin to lower blood glucose levels (n = 145) and those receiving no insulin (n = 98), to determine the differences in morbidity and mortality. Patients 0 to 18 years old with burns covering ≥ 30% of the total body surface area and not randomized to receive anabolic agents were included in this study. End points included glucose levels, infections, resting energy expenditure, lean body mass, bone mineral content, fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes. Maximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent, with older children requiring more insulin (p < 0.05). Daily maximum and daily minimum, but not 6 am, glucose levels were significantly different based on treatment group (p < 0.05). Insulin significantly increased resting energy expenditure and improved bone mineral content (p < 0.05). Each additional wound infection increased incidence of hyperglycemia (p = 0.004). There was no mortality in patients not receiving insulin, only in patients who received insulin (p < 0.004). Muscle strength was increased in patients receiving insulin (p < 0.05). Burn-induced hyperglycemia develops in a subset of severely burned children. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted bone mineral content and muscle strength, but increased resting energy expenditure, hypoglycemic episodes, and mortality. New glucose-lowering strategies might be needed. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

PubMed

Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

2015-11-01

On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

Factors Affecting Employment Among Informal Caregivers Assisting People with Multiple Sclerosis

PubMed Central

Huang, Chunfeng; Zheng, Zhida

2013-01-01

The objective of this study was to identify characteristics of informal caregivers, caregiving, and the people with multiple sclerosis (MS) receiving assistance that are associated with reduced caregiver employment. Data were collected during telephone interviews with 530 MS caregivers, including 215 employed caregivers, with these survey data analyzed using logistic regression. Poorer cognitive ability by the care recipient to make decisions about daily tasks and more caregiving hours per week predicted reduced caregiver employment. Better physical health domains of caregiver quality of life were associated with significantly lower odds of reduced employment. Health professionals treating informal caregivers, as well as those treating people with MS, need to be aware of respite, support, and intervention programs available to MS caregivers and refer them to these programs, which could reduce the negative impact of caregiving on employment. PMID:24453784

The Experience of Persons With Multiple Sclerosis Using MS INFoRm: An Interactive Fatigue Management Resource.

PubMed

Pétrin, Julie; Akbar, Nadine; Turpin, Karen; Smyth, Penelope; Finlayson, Marcia

2018-04-01

We aimed to understand participants' experiences with a self-guided fatigue management resource, Multiple Sclerosis: An Interactive Fatigue Management Resource ( MS INFoRm), and the extent to which they found its contents relevant and useful to their daily lives. We recruited 35 persons with MS experiencing mild to moderate fatigue, provided them with MS INFoRm, and then conducted semistructured interviews 3 weeks and 3 months after they received the resource. Interpretive description guided the analysis process. Findings indicate that participants' experience of using MS INFoRm could be understood as a process of change, influenced by their initial reactions to the resource. They reported experiencing a shift in knowledge, expectations, and behaviors with respect to fatigue self-management. These shifts led to multiple positive outcomes, including increased levels of self-confidence and improved quality of life. These findings suggest that MS INFoRm may have a place in the continuum of fatigue management interventions for people with MS.

Daily Bathing with Chlorhexidine and Its Effects on Nosocomial Infection Rates in Pediatric Oncology Patients.

PubMed

Raulji, Chittalsinh M; Clay, Kristin; Velasco, Cruz; Yu, Lolie C

2015-01-01

Infections remain a serious complication in pediatric oncology patients. To determine if daily bathing with Chlorhexidine gluconate can decrease the rate of nosocomial infection in pediatric oncology patients, we reviewed rates of infections in pediatric oncology patients over a 14-month span. Intervention group received daily bath with Chlorhexidine, while the control group did not receive daily bath. The results showed that daily bath with antiseptic chlorhexidine as daily prophylactic antiseptic topical wash leads to decreased infection density amongst the pediatric oncology patients, especially in patients older than 12 years of age. Furthermore, daily chlorhexidine bathing significantly reduced the rate of hospital acquired infection in patients older than 12 years of age. The findings of this study suggest that daily bathing with chlorhexidine may be an effective measure of reducing nosocomial infection in pediatric oncology patients.

Continuous subcutaneous insulin infusion preserves axonal function in type 1 diabetes mellitus.

PubMed

Kwai, Natalie; Arnold, Ria; Poynten, Ann M; Lin, Cindy S-Y; Kiernan, Matthew C; Krishnan, Arun V

2015-02-01

Diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. Although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown. In the present study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical neurological assessment. Subsequently, 41 non-neuropathic patients, 24 of whom were receiving multiple daily insulin injections (MDII) and 17 receiving continuous subcutaneous insulin infusion (CSII), underwent nerve excitability testing, a technique that assesses axonal ion channel function and membrane potential in human nerves. Treatment groups were matched for glycaemic control, body mass index, disease duration and gender. Neurophysiological parameters were compared between treatment groups and those taken from age and sex-matched normal controls. Prominent differences in axonal function were noted between MDII-treated and CSII-treated patients. Specifically, MDII patients manifested prominent abnormalities when compared with normal controls in threshold electrotonus (TE) parameters including depolarizing TE(10-20ms), undershoot and hyperpolarizing TE (90-100 ms) (P < 0.05). Additionally, recovery cycle parameters superexcitability and subexcitability were also abnormal (P < 0.05). In contrast, axonal function in CSII-treated patients was within normal limits when compared with age-matched controls. The differences between the groups were noted in cross-sectional analysis and remained at longitudinal follow-up. Axonal function in type 1 diabetes is maintained within normal limits in patients treated with continuous subcutaneous insulin infusion and not with multiple daily insulin injections. This raises the possibility that CSII therapy may have neuroprotective potential in patients with type 1 diabetes. Copyright © 2014 John Wiley & Sons, Ltd.

Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin tumor response and neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, J.L.; Biol, F.I.; Patterson, I.C.M.

1982-03-01

In 1978, a pilot study began of 29 patients with advanced tumors of the head and neck. The study showed an initial peripheral neuropathy rate of 55%, despite a dose limitation of 12 g/m/sup 2/ of misonidazole. Tumor response at 9 months was most encouraging. We are now able to examine tumor response and persistence of neuropathy in these patients 2 1/2 years after radical radiotherapy. The results are comparable with those obtained with hyperbaric oxygen in a clinical trial at this center during the 1970's. Neuropathy was a serious side effect but the drug phenytoin has been shown tomore » shorten the half-life of misonidazole. We have examined the effect of phenytoin on the pharmacokinetics of misonidazole in 13 patients who received radical radiotherapy for advanced head and neck tumors or oesophageal tumors. Misonidazole was given in multiple doses, i.e. daily or weekly as it would be used in conventional therapy. Phenytoin was given either daily throughout treatment, or it was withdrawn during treatment. There were dramatic changes in the half-life of misonidazole, but the concentration at the time of irradiation was little affected. The significant changes in the half-life of misonidazole and the increased concentration of the metabolite desmethylmisonidazole are discussed.« less

[Treatment of chronic postinfectious fatigue: randomized double-blind study of two doses of sulbutiamine (400-600 mg/day) versus placebo].

PubMed

Tiev, K P; Cabane, J; Imbert, J C

1999-10-01

Chronic fatigue remains a medical mystery and a therapeutic failure. The subgroup of chronic fatigue postinfectious fatigue (CPIF) is an interesting one since it is quite frequent in general practice. We studied sulbutiamine (Su), isobutyryl-thiamine disulfide in this context. We included 326 general-practice patients suffering from CPIF: they received randomly either Su, 400 mg daily (n = 106), or Su, 600 mg daily (n = 111), or placebo (n = 109) for 28 days in a double-blind, parallel-group study. 315 patients completed the study. The evaluation of fatigue, by multiple means including mainly MFI, a validated multidimensional fatigue scale, showed overall no significant difference between the groups. On the 7th day, however, women receiving Su, 600 mg had less fatigue (P < 0.01), but the figures were quite diverse and no persistent effect was noted at the 28th day. Thus, we showed for the first time that a high level general-practice study of fatigue is feasible using specific tools. Whether the effect observed after 1 week in women represents a true finding needs additional research. Further studies are in progress in order to characterize better the potential usefulness of Su in chronic fatigue.

Mission Planning and Scheduling System for NASA's Lunar Reconnaissance Mission

NASA Technical Reports Server (NTRS)

Garcia, Gonzalo; Barnoy, Assaf; Beech, Theresa; Saylor, Rick; Cosgrove, Jennifer Sager; Ritter, Sheila

2009-01-01

In the framework of NASA's return to the Moon efforts, the Lunar Reconnaissance Orbiter (LRO) is the first step. It is an unmanned mission to create a comprehensive atlas of the Moon's features and resources necessary to design and build a lunar outpost. LRO is scheduled for launch in April, 2009. LRO carries a payload comprised of six instruments and one technology demonstration. In addition to its scientific mission LRO will use new technologies, systems and flight operations concepts to reduce risk and increase productivity of future missions. As part of the effort to achieve robust and efficient operations, the LRO Mission Operations Team (MOT) will use its Mission Planning System (MPS) to manage the operational activities of the mission during the Lunar Orbit Insertion (LOI) and operational phases of the mission. The MPS, based on GMV's flexplan tool and developed for NASA with Honeywell Technology Solutions (prime contractor), will receive activity and slew maneuver requests from multiple science operations centers (SOC), as well as from the spacecraft engineers. flexplan will apply scheduling rules to all the requests received and will generate conflict free command schedules in the form of daily stored command loads for the orbiter and a set of daily pass scripts that help automate nominal real-time operations.

Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats

PubMed Central

Noor, Neveen A; Fahmy, Heba M; Mohammed, Faten F; Elsayed, Anwar A; Radwan, Nasr M

2015-01-01

Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE-induced rats were divided into: 1- EAE-induced rats (“EAE” group). 2- “N. sativa + EAE” group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- “EAE + N. sativa” group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF β1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE. PMID:26261504

Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

PubMed

Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

2017-11-01

To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (C_max), and plasma concentrations at the end of the dosing interval (C_τ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80.00 - 125.00%. Bioavailability of OOD was not influenced by concomitant food intake. OOD and OTD were generally well tolerated, a difference between the two products could not be observed. The new 10-mg OOD formulation provides sustained oxycodone plasma concentrations over the dosing interval of 24 hours and is suitable for once-daily administration. Bioavailability of OOD could be classified as comparable to the twice-daily administration of the OTD reference formulation. The new formulation widens and optimizes the range of strong opioid drug products in patient-centered therapy of chronic pain with simplified dosing and better compliance.
.

Fingolimod in relapsing multiple sclerosis: An integrated analysis of safety findings.

PubMed

Kappos, Ludwig; Cohen, Jeffrey; Collins, William; de Vera, Ana; Zhang-Auberson, Lixin; Ritter, Shannon; von Rosenstiel, Philipp; Francis, Gordon

2014-07-01

Fingolimod 0.5mg once daily is the first approved oral therapy for relapsing multiple sclerosis (MS). To report integrated long-term safety data from phase 2/3 fingolimod studies. Descriptive safety data are reported from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study, a 24-month, randomized, double-blind study comparing fingolimod 0.5mg and 1.25mg with placebo, and an All Studies group (patients who received fingolimod 0.5mg (n=1640) or 1.25-0.5mg (n=1776) in phase 2/3 studies and associated extensions). Relevant post-marketing experience, up to December 2011, is included. The incidence of adverse events (AEs) and serious AEs (SAEs) was similar with fingolimod and placebo in FREEDOMS. In the All Studies group, fingolimod 0.5mg was associated with transient, rarely symptomatic (0.5%), bradycardia and second-degree atrioventricular block on treatment initiation, minor blood pressure increases, frequent (9%) but generally asymptomatic liver enzyme elevations, and macular oedema (0.4%). The incidences of infections (including serious and herpes infections), malignancies, SAEs and treatment discontinuations due to AEs were similar with fingolimod 0.5mg and placebo. The safety profile of fingolimod has been well characterized in this large combined trial population. Although infrequent SAEs can occur, there is no increased risk of infections, malignancies or serious cardiovascular events versus placebo. Copyright © 2014. Published by Elsevier B.V.

Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

PubMed

Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

2017-01-01

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Effect of a randomised exclusive breastfeeding counselling intervention nested into the MINIMat prenatal nutrition trial in Bangladesh.

PubMed

Khan, Ashraful Islam; Kabir, Iqbal; Eneroth, Hanna; El Arifeen, Shams; Ekström, Eva-Charlotte; Frongillo, Edward A; Persson, Lars Åke

2017-01-01

It is unknown whether maternal malnutrition reduces the effect of counselling on exclusive breastfeeding. This study evaluated the effect of breastfeeding counselling on the duration of exclusive breastfeeding, and whether the timing of prenatal food and different micronutrient supplements further prolonged this duration. Pregnant women in Matlab, Bangladesh, were randomised to receive daily food supplements of 600 kcal at nine weeks of gestation or at the standard 20 weeks. They also were allocated to either 30 mg of iron and 400 μg folic acid, or the standard programme 60 mg of iron and folic acid or multiple micronutrients. At 30 weeks of gestation, 3188 women were randomised to receive either eight breastfeeding counselling sessions or the usual health messages. The median duration of exclusive breastfeeding was 135 days in the counselling group and 75 days in the usual health message group (p < 0.001). Prenatal supplements did not modify the effects of counselling. Women in the usual health message group who were randomised to multiple micronutrients exclusively breastfed for 12 days longer than mothers receiving the standard iron-folate combination (p = 0.003). Breastfeeding counselling increased the duration of exclusive breastfeeding by 60 days. This duration was not influenced by the supplements. ©2016 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

The influence of parenteral glutamine supplementation on glucose homeostasis in critically ill polytrauma patients--A randomized-controlled clinical study.

PubMed

Grintescu, Ioana Marina; Luca Vasiliu, Irina; Cucereanu Badica, Ioana; Mirea, Liliana; Pavelescu, Daniela; Balanescu, Andreea; Grintescu, Ioana Cristina

2015-06-01

Rapid onset of resistance to insulin is a prominent component of stress metabolism in multiple trauma patients. Recent studies have clarified the role of amino acids (especially glutamine) in glucose transportation and the benefits of parenteral alanyl-glutamine supplementation (0.3-0.6 g/kg/day) in glucose homeostasis. The aims of this study are to evaluate the incidence of hyperglycemic episodes and the need for exogenous insulin to maintain stable glucose levels in critically ill polytrauma patients supplemented with parenteral glutamine dipeptide (Dipeptiven(®)) versus standard nutritional support. This was an open-label randomized-controlled trial of 82 polytrauma patients aged 20-60 years old, randomly assigned into two equal groups independent of sex, age and Injury Severity Score. We excluded patients with diabetes mellitus, or renal or hepatic failure. One group received parenteral Dipeptiven(®) supplementation of 0.5 g/kg/day and the other received standard isocaloric isoproteinic nutritional support. We found that 63% of patients in the glutamine-supplemented group had no hyperglycemic episodes; only 37% required exogenous insulin (mean daily requirement of 44 units/day). In the control group, 51% of patients required insulin (mean daily requirement 63 unit/day; p = 0.0407). The effect of glutamine supplementation on glucose homeostasis is associated with a lower incidence of hyperglycemia among critically ill polytrauma patients, and leads to a lower mean daily dose of insulin. Controlled-trials.com Identifier: ISRCTN71592366 (http://www.controlled-trials.com/ISRCTN71592366/ISRCTN71592366). Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Dalfampridine in Parkinson's disease related gait dysfunction: A randomized double blind trial.

PubMed

Luca, Corneliu C; Nadayil, Gloria; Dong, Chuanhui; Nahab, Fatta B; Field-Fote, Edelle; Singer, Carlos

2017-08-15

Disease-related gait dysfunction causes extensive disability for persons with Parkinson's disease (PD), with no effective therapies currently available. The potassium channel blocker dalfampridine has been used in multiple neurological conditions and improves walking in persons with multiple sclerosis. We aimed to evaluate the effect of dalfampridine extended release (D-ER) 10mg tablets twice daily on different domains of walking in participants with PD. Twenty-two participants with PD and gait dysfunction were randomized to receive D-ER 10mg twice daily or placebo for 4weeks in a crossover design with a 2-week washout period. The primary outcomes were change in the gait velocity and stride length. At 4weeks, gait velocity was not significantly different between D-ER (0.89m/s±0.33) and placebo (0.93m/s±0.27) conditions. The stride length was also similar between conditions: 0.96m±0.38 for D-ER versus 1.06m±0.33 for placebo. D-ER was generally well tolerated with the most frequent side effects being dizziness, nausea and balance problems. D-ER is well tolerated in PD patients, however it did not show significant benefit for gait impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

Power-law scaling in daily rainfall patterns and consequences in urban stream discharges

NASA Astrophysics Data System (ADS)

Park, Jeryang; Krueger, Elisabeth H.; Kim, Dongkyun; Rao, Suresh C.

2016-04-01

Poissonian rainfall has been frequently used for modelling stream discharge in a catchment at the daily scale. Generally, it is assumed that the daily rainfall depth is described by memoryless exponential distribution which is transformed to stream discharge, resulting in an analytical pdf for discharge [Gamma distribution]. While it is true that catchment hydrological filtering processes (censored by constant rate ET losses, and first-order recession) increases "memory", reflected in 1/f noise in discharge time series. Here, we show that for urban watersheds in South Korea: (1) the observation of daily rainfall depths follow power-law pdfs, and spectral slopes range between 0.2 ~ 0.4; and (2) the stream discharge pdfs have power-law tails. These observation results suggest that multiple hydro-climatic factors (e.g., non-stationarity of rainfall patterns) and hydrologic filtering (increasing impervious area; more complex urban drainage networks) influence the catchment hydrologic responses. We test the role of such factors using a parsimonious model, using different types of daily rainfall patterns (e.g., power-law distributed rainfall depth with Poisson distribution in its frequency) and urban settings to reproduce patterns similar to those observed in empirical records. Our results indicate that fractality in temporally up-scaled rainfall, and the consequences of large extreme events are preserved as high discharge events in urbanizing catchments. Implications of these results to modeling urban hydrologic responses and impacts on receiving waters are discussed.

Modeling spray drift and runoff-related inputs of pesticides to receiving water.

PubMed

Zhang, Xuyang; Luo, Yuzhou; Goh, Kean S

2018-03-01

Pesticides move to surface water via various pathways including surface runoff, spray drift and subsurface flow. Little is known about the relative contributions of surface runoff and spray drift in agricultural watersheds. This study develops a modeling framework to address the contribution of spray drift to the total loadings of pesticides in receiving water bodies. The modeling framework consists of a GIS module for identifying drift potential, the AgDRIFT model for simulating spray drift, and the Soil and Water Assessment Tool (SWAT) for simulating various hydrological and landscape processes including surface runoff and transport of pesticides. The modeling framework was applied on the Orestimba Creek Watershed, California. Monitoring data collected from daily samples were used for model evaluation. Pesticide mass deposition on the Orestimba Creek ranged from 0.08 to 6.09% of applied mass. Monitoring data suggests that surface runoff was the major pathway for pesticide entering water bodies, accounting for 76% of the annual loading; the rest 24% from spray drift. The results from the modeling framework showed 81 and 19%, respectively, for runoff and spray drift. Spray drift contributed over half of the mass loading during summer months. The slightly lower spray drift contribution as predicted by the modeling framework was mainly due to SWAT's under-prediction of pesticide mass loading during summer and over-prediction of the loading during winter. Although model simulations were associated with various sources of uncertainties, the overall performance of the modeling framework was satisfactory as evaluated by multiple statistics: for simulation of daily flow, the Nash-Sutcliffe Efficiency Coefficient (NSE) ranged from 0.61 to 0.74 and the percent bias (PBIAS) < 28%; for daily pesticide loading, NSE = 0.18 and PBIAS = -1.6%. This modeling framework will be useful for assessing the relative exposure from pesticides related to spray drift and runoff in receiving waters and the design of management practices for mitigating pesticide exposure within a watershed. Published by Elsevier Ltd.

Uncertainties in endocrine substitution therapy for central hypocortisolism.

PubMed

Swords, Francesca M

2014-01-01

Central hypocortisolism is common, and has multiple potential causes. However, the treatment aims remain the same whatever the cause: to maximize quality of life, while minimizing treatment-related adverse effects. The majority of patients with central hypocortisolism now receive hydrocortisone in two to three divided doses with a total daily dose of 10-20mg, or a weight-based regimen of 8.1mg/m(2)/day. However, various areas of controversy remain: how to assess the patient with suspected hypocortisolism, which is the optimal agent to use, what is the optimal total daily dose, how to administer divided daily doses, how to monitor therapy and individually tailor doses, whether to replace other adrenal androgens, how to approach the patient with adrenal suppression, and how to best educate patients with hypocortisolism and treat them in emergency situations. This chapter will discuss the evidence behind each of these controversial areas in turn. The evidence for newer agents such as prolonged- and delayed-release preparations of hydrocortisone will also be explored, with a discussion on their potential role in the future management of this major clinical problem. © 2014 Elsevier B.V. All rights reserved.

Effect of the cooling suit method applied to individuals with multiple sclerosis on fatigue and activities of daily living.

PubMed

Özkan Tuncay, Fatma; Mollaoğlu, Mukadder

2017-12-01

To determine the effects of cooling suit on fatigue and activities of daily living of individuals with multiple sclerosis. Fatigue is one of the most common symptoms in people with multiple sclerosis and adversely affects their activities of daily living. Studies evaluating fatigue associated with multiple sclerosis have reported that most of the fatigue cases are related to the increase in body temperature and that cooling therapy is effective in coping with fatigue. This study used a two sample, control group design. The study sample comprised 75 individuals who met the inclusion criteria. Data were collected with study forms. After the study data were collected, cooling suit treatment was administered to the experimental group. During home visits paid at the fourth and eighth weeks after the intervention, the aforementioned scales were re-administered to the participants in the experimental and control groups. The analyses performed demonstrated that the severity levels of fatigue experienced by the participants in the experimental group wearing cooling suit decreased. The experimental group also exhibited a significant improvement in the participants' levels of independence in activities of daily living. The cooling suit worn by individuals with multiple sclerosis was determined to significantly improve the participants' levels of fatigue and independence in activities of daily living. The cooling suit therapy was found to be an effective intervention for the debilitating fatigue suffered by many multiple sclerosis patients, thus significantly improving their level of independence in activities of daily living. © 2017 John Wiley & Sons Ltd.

Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds.

PubMed

Chang, Yung-Yee; Liu, Jia-Shou; Lai, Shung-Lon; Wu, Hsiu-Shan; Lan, Min-Yu

2008-01-01

Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinolytic activity. Cerebral microbleed is remnant of blood extravasations from the damaged vessels related to cerebral microangiopathies. We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time.

Genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid in multiples organs of Wistar rats.

PubMed

Larangeira, Paula Martins; de Rosso, Veridiana Vera; da Silva, Victor Hugo Pereira; de Moura, Carolina Foot Gomes; Ribeiro, Daniel Araki

2016-11-01

The ionic liquid or melted salt 1-Butyl-3-methylimidazolium is an alternative process to extract natural pigments, such as carotenoids. Lycopene represents 80-90% of total of carotenoids presents in tomatoes and it has been widely studied due its potent antioxidant action. The aim of this study was to evaluate genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid using experimental model in vivo. For this purpose, a total of 20 male Wistar rats were distributed into four groups (n=5), as follows: control group; received a corresponding amount of corn oil for 7days by intragastric gavage (i.g.), ionic liquid group, received 10mgkg -1 body weight for 7days by gavage; 10mg carotenoids group, received 10mgkg -1 bw dissolved in corn oil for 7days by gavage and 500mg carotenoids group, received 500mgkg -1 bw dissolved in corn oil for 7days by gavage. Rat liver treated with ionic liquid exhibited moderate histopathological changes randomly distributed in the parenchyma, such as cytoplasmic eosinophilia, apoptotic bodies, inflammatory infiltrate and focal necrosis. DNA damage was found in peripheral blood and liver cells of rats treated with ionic liquid or carotenoids at 500mg. An increase of micronucleated cells and 8-OhDG immunopositive cells were also detected in rats treated with carotenoids at 500mg. In summary, our results demonstrate that recommended dose for human daily intake of carotenoids extracted by ionic liquid did not induce genotoxicity, mutagenicity and cytotoxicity in multiple organs of rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

Minimal Clinically Important Difference of Berg Balance Scale in People With Multiple Sclerosis.

PubMed

Gervasoni, Elisa; Jonsdottir, Johanna; Montesano, Angelo; Cattaneo, Davide

2017-02-01

To identify the minimal clinically important difference (MCID) to define clinically meaningful patient's improvement on the Berg Balance Scale (BBS) in people with multiple sclerosis (PwMS) in response to rehabilitation. Cohort study. Neurorehabilitation institute. PwMS (N=110). This study comprised inpatients and outpatients who participated in research on balance and gait rehabilitation. All received 20 rehabilitation sessions with different intensities. Inpatients received daily treatments over a period of 4 weeks, while outpatients received 2 to 3 treatments per week for 10 weeks. An anchor-based approach using clinical global impression of improvement in balance (Activities-specific Balance Confidence [ABC] Scale) was used to determine the MCID of the BBS. The MCID was defined as the minimum change in the BBS total score (postintervention - preintervention) that was needed to perceive at least a 10% improvement on the ABC Scale. Receiver operating characteristic curves were used to define the cutoff of the optimal MCID of the BBS discriminating between improved and not improved subjects. The MCID for change on the BBS was 3 points for the whole sample, 3 points for the inpatients, and 2 points for the outpatients. The area under the curve was .65 for the whole sample, .64 for inpatients, and .68 for outpatients. The MCID for improvement in balance as measured by the BBS was 3 points, meaning that PwMS are likely to perceive that as a reproducible and clinically important change in their balance performance. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Successful treatment with a combination of lenalidomide and dexamethasone for cryoglobulinemia associated with multiple myeloma].

PubMed

Taniguchi, Hiroaki; Imaizumi, Yoshitaka; Makiyama, Junya; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Tsushima, Hideki; Hata, Tomoko; Miyazaki, Yasushi

2014-08-01

Cryoglobulinemia (Cg) in multiple myeloma (MM) is rare and no standard treatment has yet been established. Herein, we report a case of MM with Cg, successfully treated with a combination of lenalidomide and dexamethasone. A 76-year-old woman suffering from skin ulcerations, extremity pain and peripheral neuropathy was diagnosed as having IgG-kappa MM with Cg in 1992. She intermittently received conventional chemotherapy, immunosuppressant therapy and plasma exchange. Despite these treatments, Cg-related symptoms eventually became uncontrollable. She was admitted to our hospital in 2012 because of worsening skin symptoms involving both ankles. Plasmapheresis proved ineffective. Improvement of skin ulcerations and numbness was achieved with administration of lenalidomide at 25 mg daily with weekly dexamethasone, which also decreased the cryoglobulin level. The course of this patient suggests that lenalidomide plus dexamethasone is a promising treatment for MM with Cg.

Acceptability Among Community Healthcare Nurses of Intelligent Wireless Sensor-system Technology for the Rapid Detection of Health Issues in Home-dwelling Older Adults.

PubMed

Cohen, Christine; Kampel, Thomas; Verloo, Henk

2017-01-01

The effective care and support of community healthcare nurses (CHNs) contribute greatly to the healthy aging of older adults living at home. Integrating innovative technologies into CHNs' daily practice offers new opportunities and perspectives for early detection of health issues and interventions among home-dwelling older adults. To explore the perception of acceptability among CHNs of an intelligent wireless sensor system (IWSS) for use in daily practice for the detection of health issues in home-dwelling older adults receiving home healthcare. Descriptive and qualitative data were sourced from a pilot randomized controlled trial involving 17 CHNs using an IWSS in their daily practice to rapidly detect falls and other health issues in patients' homes. IWSS alerts indicating behavior changes were sent to CHNs. Their perceived usefulness (PU) and perceived ease of use (PEOU) were assessed. The acceptability of IWSS technology was explored using a questionnaire and focus group discussions. The PU and PEOU of the IWSS technology were low to moderate. A majority of the CHNs were dissatisfied with its performance and intrusiveness; they reported multiple obstacles in the usefulness and ease of use of the IWSS technology in daily practice. To improve the IWSS technology's low to moderate acceptability among CHNs, we recommend a more user-centered implementation strategy and an embedded model of nursing care.

Evaluating the Benefits of Aphasia Intervention Delivered in Virtual Reality: Results of a Quasi-Randomised Study.

PubMed

Marshall, Jane; Booth, Tracey; Devane, Niamh; Galliers, Julia; Greenwood, Helen; Hilari, Katerina; Talbot, Richard; Wilson, Stephanie; Woolf, Celia

2016-01-01

This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks' intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings.

Evaluating the Benefits of Aphasia Intervention Delivered in Virtual Reality: Results of a Quasi-Randomised Study

PubMed Central

Marshall, Jane; Booth, Tracey; Devane, Niamh; Galliers, Julia; Greenwood, Helen; Hilari, Katerina; Talbot, Richard; Wilson, Stephanie; Woolf, Celia

2016-01-01

Introduction This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks’ intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. Results There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings. PMID:27518188

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

PubMed

Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

2016-01-01

Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

A Comparison of Daily Average Consumption Of Oxycodone Controlled Release (OxyContin CR) And Oxymorphone Extended Release (Opana ER) In Patients With Low Back Pain.

PubMed

Berner, Todd; Thomson, Heather; Hartry, Ann; Puenpatom, R Amy; Ben-Joseph, Rami; Szeinbach, Sheryl L

2011-03-01

Our goal was to examine the daily average consumption (DACON) of oxycodone controlled-release tablets (OxyContin CR)and oxymorphone extended-release tablets (Opana ER) in patients with low back pain. An observational, retrospective cohort study enrolled patients with multiple prescriptions for oxycodone CR or oxymorphone ER tablets. These patients also had International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for low back pain. Pharmacy prescription medication claims data were obtained from a large commercially insured health plan in the U.S. Mean daily consumption was calculated for a 90-day period. We used descriptive statistics to evaluate patient demographics and health plan characteristics. Univariate analyses were used to examine the data as observed. A generalized linear model with a gamma distribution and log-link function provided a sensitivity measure, adjusting for heterogeneity among patients and the skewed nature of the DACON variable. A total of 4,023 patients received oxycodone CR, and 374 patients received oxymorphone ER. The mean age of patients (standard deviation, SD) was 49.0 (11.6) years for oxycodone CR and 47.3 (10.6) years for oxymorphone ER. DACON of oxycodone CR was 3.2 tablets per day, and DACON of oxymorphone ER was 2.7 tablets per day (P < 0.01). Utilization of maximum-strength tablets of oxycodone CR 80 mg was 3.9 tablets per day, which was significantly higher, by one tablet per day, than the utilization of equipotent oxymorphone ER maximum-strength tablets of 40 mg at 2.9 tablets per day (P < 0.01). The use of oxycodone CR, measured as mean daily consumption over a 90-day period, was significantly higher than that for oxymorphone ER in these patients, a finding that could have financial implications for health care systems.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

PubMed

Metz, Luanne M; Li, David K B; Traboulsee, Anthony L; Duquette, Pierre; Eliasziw, Misha; Cerchiaro, Graziela; Greenfield, Jamie; Riddehough, Andrew; Yeung, Michael; Kremenchutzky, Marcelo; Vorobeychik, Galina; Freedman, Mark S; Bhan, Virender; Blevins, Gregg; Marriott, James J; Grand'Maison, Francois; Lee, Liesly; Thibault, Manon; Hill, Michael D; Yong, V Wee

2017-06-01

On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T 2 -weighted MRI, cumulative number of new lesions enhanced on T 1 -weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T 1 -weighted MRI plus new and newly enlarged lesions on T 2 -weighted MRI]). A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo. The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial.

PubMed

Karakochuk, Crystal D; Barker, Mikaela K; Whitfield, Kyly C; Barr, Susan I; Vercauteren, Suzanne M; Devlin, Angela M; Hutcheon, Jennifer A; Houghton, Lisa A; Prak, Sophonneary; Hou, Kroeun; Chai, Tze Lin; Stormer, Ame; Ly, Sokhoing; Devenish, Robyn; Oberkanins, Christian; Pühringer, Helene; Harding, Kimberly B; De-Regil, Luz M; Kraemer, Klaus; Green, Tim J

2017-07-01

Background: Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy. Objective: We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic. Design: In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. Results: In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction ( P = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) ( P < 0.001) among women who received iron ( n = 407) and 1.2 g/L (-0.6, 3.0 g/L) ( P = 0.18) among women who received MMNs ( n = 407). The predicted proportions (95% CIs) of women with a hemoglobin response (≥10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively. Conclusions: Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at clinicaltrials.gov as NCT02481375. © 2017 American Society for Nutrition.

Supplementation of suckling beef calves with different levels of crude protein on tropical pasture.

PubMed

Lopes, Sidnei Antonio; Paulino, Mário Fonseca; Detmann, Edenio; de Campos Valadares Filho, Sebastião; Valente, Eriton Egídio Lisboa; Barros, Lívia Vieira; Cardenas, Javier Enrique Garces; Almeida, Daniel Mageste; Martins, Leandro Soares; Silva, Aline Gomes

2014-02-01

The effects of supplementation with different levels of crude protein on performance, intake and nutrient digestibility and efficiency of microbial protein synthesis in suckling beef calves on pasture were assessed. Fifty-five calves, with an average age of 100 days and an initial average body weight of 110 ± 7.5 kg and their respective dams, were used. The experimental design was completely randomised with five treatments and 11 replications. The experimental treatments for calves were as follows: control = calves received only mineral mixture; supplementation levels = calves received supplement containing 8, 19, 30 or 41% of crude protein (CP, at a rate of 0.5% of body weight (BW)). The cows received only mineral mixture ad libitum. Supplemented calves had higher (P < 0.1) average daily gain (ADG). Protein levels showed a quadratic effect (P < 0.1) on average daily gain (ADG) of calves. There was no difference in total dry matter (DM) intake (P > 0.1). However, intake of dry matter forage (DMF) presented cubic profiles (P < 0.1), with CP levels in the supplements. Supplementation increased (P < 0.1) the digestibility of nutrients, except for the digestibility of neutral detergent fibre. Supplementation increased (P < 0.1) the production of microbial nitrogen and N losses in urine. It can be concluded that multiple supplementations optimise the performance of beef calves on creep feeding. The intake of supplements with CP levels between 8 and 30% partially replaces of the pasture ingested by calves and increases the digestibility of the diet.

Short daily-, nocturnal- and conventional-home hemodialysis have similar patient and treatment survival.

PubMed

Tennankore, Karthik K; Na, Yingbo; Wald, Ron; Chan, Christopher T; Perl, Jeffrey

2018-01-01

Home hemodialysis (HHD) has many benefits, but less is known about relative outcomes when comparing different home-based hemodialysis modalities. Here, we compare patient and treatment survival for patients receiving short daily HHD (2-3 hours/5 plus sessions per week), nocturnal HHD (6-8 hours/5 plus sessions per week) and conventional HHD (3-6 hours/2-4 sessions per week). A nationally representative cohort of Canadian HHD patients from 1996-2012 was studied. The primary outcome was death or treatment failure (defined as a permanent return to in-center hemodialysis or peritoneal dialysis) using an intention to treat analysis and death-censored treatment failure as a secondary outcome. The cohort consisted of 600, 508 and 202 patients receiving conventional, nocturnal, and short daily HHD, respectively. Conventional-HHD patients were more likely to use dialysis catheter access (43%) versus nocturnal or short daily HHD (32% and 31%, respectively). Although point estimates were in favor of both therapies, after multivariable adjustment for patient and center factors, there was no statistically significant reduction in the relative hazard for the death/treatment failure composite comparing nocturnal to conventional HHD (hazard ratio 0.83 [95% confidence interval 0.66-1.03]) or short daily to conventional HHD (0.84, 0.63-1.12). Among those with information on vascular access, patients receiving nocturnal HHD had a relative improvement in death-censored treatment survival (0.75, 0.57-0.98). Thus, in this national cohort of HHD patients, those receiving short daily and nocturnal HHD had similar patient/treatment survival compared with patients receiving conventional HHD. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Andrographis paniculata extract (HMPL-004) for active ulcerative colitis.

PubMed

Sandborn, William J; Targan, Stephan R; Byers, Vera S; Rutty, Dean A; Mu, Hua; Zhang, Xun; Tang, Tom

2013-01-01

Andrographis paniculata has in vitro inhibitory activity against TNF-α, IL-1β and NF-κB. A pilot study of A. paniculata extract (HMPL-004) suggested similar efficacy to mesalamine for ulcerative colitis. A randomized, double-blind, placebo-controlled trial evaluated the efficacy of A. paniculata extract (HMPL-004) in 224 adults with mild-to-moderate ulcerative colitis. Patients were randomized to A. paniculata extract (HMPL-004) 1,200 mg or 1,800 mg daily or placebo for 8 weeks. In total, 45 and 60% of patients receiving A. paniculata 1,200 mg and 1,800 mg daily, respectively, were in clinical response at week 8, compared with 40% of those who received placebo (P=0.5924 for 1,200 mg vs. placebo and P=0.0183 for 1,800 mg vs. placebo). In all, 34 and 38% of patients receiving A. paniculata 1,200 mg and 1,800 mg daily, respectively, were in clinical remission at week 8, compared with 25% of those who received placebo (P=0.2582 for 1,200 mg vs. placebo and P=0.1011 for 1,800 mg vs. placebo). Adverse events developed in 60 and 53% of patients in the A. paniculata 1,200 mg and 1,800 mg daily groups, respectively, and 60% in the placebo group. Patients with mildly to moderately active ulcerative colitis treated with A. paniculata extract (HMPL-004) at a dose of 1,800 mg daily were more likely to achieve clinical response than those receiving placebo.

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

PubMed

Mathias, C J; Senard, J M; Braune, S; Watson, L; Aragishi, A; Keeling, J E; Taylor, M D

2001-08-01

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Accounting for the sedative and analgesic effects of medication changes during patient participation in clinical research studies: measurement development and application to a sample of institutionalized geriatric patients.

PubMed

Sloane, Philip; Ivey, Jena; Roth, Mary; Roederer, Mary; Williams, Christianna S

2008-03-01

To date, no system has been published that allows investigators to adjust for the overall sedative and/or analgesic effects of medications, or changes in medications, in clinical trial participants for whom medication use cannot be controlled. This is common in clinical trials of behavioral and complementary/alternative therapies, and in research involving elderly or chronically ill patients for whom ongoing medical care continues during the trial. This paper describes the development, and illustrates the use, of a method we developed to address this issue, in which we generate single continuous variables to represent the daily sedative and analgesic loads of multiple medications. Medications for 90 study participants in a clinical trial of a nonpharmacological intervention were abstracted from medication administration records across multiple treatment periods. An expert panel of three academic clinical pharmacists and a geriatrician met to develop a system by which each study medication could be assigned a sedative and analgesic effect rating. The two measures, when applied to data on 90 institutionalized persons with Alzheimer's disease, resulted in variables with moderately skewed distributions that are consistent with the clinical profile of analgesia and sedation use in long-term care populations. The average study participant received 1.89 analgesic medications per day and had a daily analgesic load of 2.96; the corresponding figures for sedation were 2.07 daily medications and an average daily load of 11.41. A system of classifying the sedative and analgesic effects of non-study medications was created that divides drugs into categories based on the strength of their effects and assigns a rating to express overall sedative and analgesic effects. These variables may be useful in comparing patients and populations, and to control for drug effects in future studies.

Validation of a contemporary adherence measure for children with Type 1 diabetes: the Diabetes Management Questionnaire

PubMed Central

Mehta, S. N.; Nansel, T. R.; Volkening, L. K.; Butler, D. A.; Haynie, D. L.; Laffel, L. M. B.

2016-01-01

Aims To evaluate the psychometric properties of the Diabetes Management Questionnaire, a brief, self-report measure of adherence to contemporary diabetes management for young people with Type 1 diabetes and their caregivers. Methods A total of 273 parent-child dyads completed parallel versions of the Diabetes Management Questionnaire. Eligible children (aged 8–18 years) had Type 1 diabetes for ≥1 year. A multidisciplinary team designed the Diabetes Management Questionnaire as a brief, self-administered measure of adherence to Type 1 diabetes management over the preceding month; higher scores reflect greater adherence. Psychometrics were evaluated for the entire sample and according to age of the child. Results The children (49% female) had a mean ± SD (range) age 13.3 ± 2.9 (8–18) years and their mean ± SD HbA1c was 71 ± 15 mmol/mol (8.6 ± 1.4%). Internal consistency was good for parents (α = 0.83) and children (a = 0.79). Test-retest reliability was excellent for parents (intraclass correlation coefficient =0.83) and good for children (intraclass correlation coefficient = 0.65). Parent and child scores had moderate agreement (intraclass correlation coefficient = 0.54). Diabetes Management Questionnaire scores were inversely associated with HbA1c (parents: r = –0.41, P < 0.0001; children: r = –0.27, P < 0.0001). Psychometrics were stronger in the children aged ≥13 years compared with those aged < 13 years, but were acceptable in both age groups. Mean ± SD Diabetes Management Questionnaire scores were higher among children who were receiving insulin pump therapy (n = 181) than in children receiving multiple daily injections (n = 92) according to parent (75.9 ± 11.8 vs. 70.5 ± 15.5; P = 0.004) and child report (72.2 ± 12.1 vs. 67.6 ± 13.9; P = 0.006). Conclusions The Diabetes Management Questionnaire is a brief, valid self-report measure of adherence to contemporary diabetes self-management for people aged 8–18 years who are receiving either multiple daily injections or insulin pump therapy. PMID:26280463

Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial.

PubMed

Hermanides, J; Nørgaard, K; Bruttomesso, D; Mathieu, C; Frid, A; Dayan, C M; Diem, P; Fermon, C; Wentholt, I M E; Hoekstra, J B L; DeVries, J H

2011-10-01

To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with Type 1 diabetes (40 women) currently treated with multiple daily injections, age 18-65 years and HbA(1c) ≥ 8.2% (≥ 66 mmol/mol) to 26 weeks of treatment with either a sensor-augmented insulin pump (n = 44) (Paradigm(®) REAL-Time) or continued with multiple daily injections (n = 39). Change in HbA(1c) between baseline and 26 weeks, sensor-derived endpoints and patient-reported outcomes were assessed. The trial was completed by 43/44 (98%) patients in the sensor-augmented insulin pump group and 35/39 (90%) patients in the multiple daily injections group. Mean HbA(1c) at baseline and at 26 weeks changed from 8.46% (SD 0.95) (69 mmol/mol) to 7.23% (SD 0.65) (56 mmol/mol) in the sensor-augmented insulin pump group and from 8.59% (SD 0.82) (70 mmol/mol) to 8.46% (SD 1.04) (69 mmol/mol) in the multiple daily injections group. Mean difference in change in HbA(1c) after 26 weeks was -1.21% (95% confidence interval -1.52 to -0.90, P < 0.001) in favour of the sensor-augmented insulin pump group. This was achieved without an increase in percentage of time spent in hypoglycaemia: between-group difference 0.0% (95% confidence interval -1.6 to 1.7, P = 0.96). There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group (P = 0.21). Problem Areas in Diabetes and Diabetes Treatment Satisfaction Questionnaire scores improved in the sensor-augmented insulin pump group. Sensor augmented pump therapy effectively lowers HbA(1c) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Using smartphones to collect daily sexual behavior data from college students.

PubMed

Willis, Malachi; Jozkowski, Kristen N

2018-02-15

Our objectives were to measure reporting differences between sexual behavior data from daily diary and retrospective estimates and to assess the utility of using smartphones to collect sexual behavior data from a college student population. Eighty-six participants (68 women, 18 men) completed the study. For 30 days during the Spring 2017 semester, participants received prompts to participate in daily diaries about their previous day's sexual behavior on their smartphones. Participants then retrospectively reported their past 30 days of sexual behavior and provided feedback on the process of receiving daily diaries on their smartphones. We found that college students overreported their sexual behavior on the retrospective survey compared to their daily diary reports (ps < .001; Cohen's ds ≥ 1.51). Participants provided positive and constructive feedback. Using smartphones to administer daily diaries is a promising technique for obtaining reliable sexual behavior data from college students.

Effects of dexpanthenol and N-acetylcysteine pretreatment in rats before renal ischemia/reperfusion injury.

PubMed

Sen, Huseyin; Deniz, Suleyman; Yedekci, A Erturk; Inangil, Gokhan; Muftuoglu, Tuba; Haholu, Aptullah; Ozkan, Sezai

2014-11-01

We investigated the anti-inflammatory and protective effects of concomitant use of dexpanthenol (DXP) and N-acetylcysteine (NAC) induced ischemia/reperfusion (I/R) injury of kidney. Forty rats were randomly divided into 5 groups. In all groups except for Group 1(Sham), renal arteries bilaterally occluded with vascular clamp for IR injury. Group 1(Sham), received a single dose of 10 mL/kg isotonic saline daily by intraperitoneal (IP) injection for three days. Group 2(IR), received a single dose of 10 mL/kg isotonic saline daily by IP injection for three days. Group 3(IR + NAC), received 300 mg/kg NAC daily by IP injection for three days. Group 4(IR + DXP), received 500 mg/kg DXP daily by IP injection for three days. Group 5(IR + NAC + DXP), received 500 mg/kg DXP and 300 mg/kg NAC daily by IP injection for three days. Serum urea (BUN), creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2, siderocalin) levels were measured as kidney function tests. TNF-α levels were measured as inflammatory marker. Tissue sections were evaluated histopathologically under light microscopy. IR + NAC + DXP group received both NAC and DXP before induction of renal I/R and as the biochemical and histopathological data revealed the results of the IR + NAC + DXP group and sham group were similar. Biochemically and histopathologically, combined use of NAC and DXP has better results when each of them used alone. We concluded that concomitant use of DXP and NAC plays a major role against I/R injury and may be useful in acute treatment of I/R induced renal failure.

Using a treatment diary to improve the medication adherence in patients with chronic myeloid leukaemia.

PubMed

Santoleri, Fiorenzo; Lasala, Ruggero; Logreco, Andrea; Ranucci, Elena; Costantini, Alberto

2018-01-01

Purpose The aim of this study was to verify whether the distribution of a treatment diary by a pharmacist could influence the adherence to oral treatment with imatinib, nilotinib, and dasatinib in patients with chronic myeloid leukaemia. Methods The level of adherence was calculated using the received daily dose/prescribed daily dose ratio and compared between patients who used a diary and those who did not. Results Forty-four (35.8%) of 123 patients with chronic myeloid leukaemia completed the diary: 20 (45.4%) receiving imatinib, 17 (38.6%) receiving nilotinib, and seven (15.9%) receiving dasatinib. Treatment adherence with the diary calculated using received daily dose/prescribed daily dose method was 93.6% (imatinib 94.9%, nilotinib 91.1%, and dasatinib 95.8%). Adherence during the period without a diary was 86.5% (84.9, 87.4, and 90%). Adherence was significantly greater with than without a diary (p < 0.0001). Conclusions The findings of this study that, in the case of chronic diseases, direct pharmacist-patient contact is important in order to maintain high levels of adherence, and a treatment diary is a valid means of doing this. According to these data, it is necessary to support similar patient-oriented programmes in order to ensure high levels of adherence and optimize drug management.

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

PubMed

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-03-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A Randomized, Double-Blind Study Assessing Changes in Cognitive Function in Indian School Children Receiving a Combination of Bacopa monnieri and Micronutrient Supplementation vs. Placebo

PubMed Central

Mitra-Ganguli, Tora; Kalita, Soumik; Bhushan, Sakshi; Stough, Con; Kean, James; Wang, Nan; Sethi, Vidhu; Khadilkar, Anuradha

2017-01-01

Several studies have indicated a chronic cognitive enhancing effect of Bacopa monnieri across different ages and cognitive impairment associated with vitamin and mineral deficiencies in children. Therefore, we investigated the effects of 4-month supplementation with a combination of B. monnieri extract and multiple micronutrients on cognitive functions in Indian school children aged 7–12 years. This was a randomized, double-blind, parallel design, single-center study in which 300 children were randomized to receive a beverage either fortified with B. monnieri and multiple micronutrients (“fortified”) or a non-fortified isocaloric equivalent (“control”) twice-daily for 4 months. Cognitive function was assessed by the Cambridge Neuropsychological Automated Test Battery (CANTAB) administered at baseline, Day 60 and Day 121. The primary endpoint was change in short-term memory (working memory) from baseline in subjects receiving “fortified” vs. “control” beverages after 4 months. Secondary endpoints included sustained attention, episodic memory, and executive function. The “fortified” beverage did not significantly improve short-term memory or any of the secondary outcomes tested relative to the “control” beverage. However, the spatial working memory “strategy” score showed significant improvement on Day 60 (difference between groups in change from baseline: −0.55; p < 0.05), but not on Day 121 due to the active intervention. Study products were well-tolerated. Reasons for these unexpected findings are discussed. PMID:29204115

Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor

PubMed Central

Frost, Charles E; Byon, Wonkyung; Song, Yan; Wang, Jessie; Schuster, Alan E; Boyd, Rebecca A; Zhang, Donglu; Yu, Zhigang; Dias, Clapton; Shenker, Andrew; LaCreta, Frank

2015-01-01

Aim Apixaban is an orally active inhibitor of coagulation factor Xa and is eliminated by multiple pathways, including renal and non-renal elimination. Non-renal elimination pathways consist of metabolism by cytochrome P450 (CYP) enzymes, primarily CYP3A4, as well as direct intestinal excretion. Two single sequence studies evaluated the effect of ketoconazole (a strong dual inhibitor of CYP3A4 and P-glycoprotein [P-gp]) and diltiazem (a moderate CYP3A4 inhibitor and a P-gp inhibitor) on apixaban pharmacokinetics in healthy subjects. Method In the ketoconazole study, 18 subjects received apixaban 10 mg on days 1 and 7, and ketoconazole 400 mg once daily on days 4–9. In the diltiazem study, 18 subjects received apixaban 10 mg on days 1 and 11 and diltiazem 360 mg once daily on days 4–13. Results Apixaban maximum plasma concentration and area under the plasma concentration–time curve extrapolated to infinity increased by 62% (90% confidence interval [CI], 47, 78%) and 99% (90% CI, 81, 118%), respectively, with co-administration of ketoconazole, and by 31% (90% CI, 16, 49%) and 40% (90% CI, 23, 59%), respectively, with diltiazem. Conclusion A 2-fold and 1.4-fold increase in apixaban exposure was observed with co-administration of ketoconazole and diltiazem, respectively. PMID:25377242

Metronidazole excretion in human milk and its effect on the suckling neonate.

PubMed Central

Passmore, C M; McElnay, J C; Rainey, E A; D'Arcy, P F

1988-01-01

1. Milk and plasma metronidazole and hydroxymetronidazole concentrations were measured in 12 breast-feeding patients following multiple doses of metronidazole (400 mg three times daily). All patients received metronidazole in combination with other broad spectrum antibiotics. 2. Plasma concentrations of both parent drug and metabolite were measured in seven suckling infants. Thirty-five infants were monitored for adverse reactions to maternal metronidazole therapy and two further groups of suckling infants, those whose mothers received either ampicillin alone or no drug therapy, were recruited as controls. 3. The mean milk to plasma ratio (M/P) was 0.9 for metronidazole and 0.76 for hydroxymetronidazole while the mean milk metronidazole concentrations (around Cmax) were 15.5 micrograms ml-1. The mean milk hydroxymetronidazole concentration was 5.7 micrograms ml-1. 4. Infant plasma metronidazole concentrations ranged from 1.27 micrograms ml-1 to 2.41 micrograms ml-1, and the corresponding hydroxymetronidazole concentrations from 1.1 to 2.4 micrograms ml-1. 5. There were no significant increases in adverse effects in infants which could be attributable to maternal metronidazole therapy. 6. Metronidazole was excreted in milk at concentrations which caused no serious reactions in the infants studied. The drug may therefore be administered at doses of 400 mg three times daily to mothers wishing to breast-feed their infants. PMID:3203060

Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE).

PubMed

2017-03-30

Objective  To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment. Design  Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial). Setting  Eight secondary care centres in England and Scotland. Participants  Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment ("dose adjustment for normal eating," DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections. Interventions  Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years. Main outcome measures  The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction. Results  317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was -0.85% with pump treatment and -0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the difference was -0.24% (-2.7 mmol/mol) in favour of pump users (95% confidence interval -0.53 to 0.05, P=0.10). Most psychosocial measures showed no difference, but pump users showed greater improvement in treatment satisfaction and some quality of life domains (dietary freedom and daily hassle) at 12 and 24 months. Conclusions  Both groups showed clinically relevant and long lasting decreases in HbA1c, rates of severe hypoglycaemia, and improved psychological measures, although few participants achieved glucose levels currently recommended by national and international guidelines. Adding pump treatment to structured training in flexible intensive insulin treatment did not substantially enhance educational benefits on glycaemic control, hypoglycaemia, or psychosocial outcomes in adults with type 1 diabetes. These results do not support a policy of providing insulin pumps to adults with poor glycaemic control until the effects of training on participants' level of engagement in intensive self management have been determined. Trial registration  Current Controlled Trials ISRCTN61215213. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

ABR Core examination preparation: results of a survey of fourth-year radiology residents who took the 2013 examination.

PubMed

Shetty, Anup S; Grajo, Joseph R; Decker, Summer; Heitkamp, Darel E; DeStigter, Kristen K; Mezwa, Duane G; Deitte, Lori

2015-01-01

A survey was administered to fourth-year radiology residents after receiving their results from the first American Board of Radiology (ABR) Core examination in 2013. The purpose was to gather information regarding resources and study strategies to share with program directors and future resident classes. An online survey was distributed to examinees nationwide. The survey included free-response and multiple choice questions that covered examination results, perceived value of enumerated study resources, case-based and didactic teaching conferences, board reviews, study materials for noninterpretive skills, multidisciplinary conference attendance, and free-form comments. Two hundred sixty-six of 1186 residents who took the Core examination responded to the survey. Some resources demonstrated a significant difference in perceived value between residents who passed the examination and residents who failed, including internal board reviews (1.10, P < .01), daily didactic conferences (1.51, P < .01), and daily case conferences (1.43, P < .01). Residents who passed reported that conferences and review sessions at their institutions were modified with multiple choice questions, audience response, and integration of clinical physics and patient safety topics compared to residents who failed. Radiology residents and residency programs have adapted their preparations for the ABR Core examination in a variety of ways. Certain practices and study tools, including daily conferences and internal board reviews, had greater perceived value by residents who passed the examination than by residents who failed. This survey provides insights that can be used to assess and modify current preparation strategies for the ABR Core examination. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Dosimetric advantages of a clinical daily adaptive plan selection strategy compared with a non-adaptive strategy in cervical cancer radiation therapy.

PubMed

van de Schoot, Agustinus J A J; de Boer, Peter; Visser, Jorrit; Stalpers, Lukas J A; Rasch, Coen R N; Bel, Arjan

2017-05-01

Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer. Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included. Non-adaptive plans were generated based on the PTV defined using the full bladder planning CT. For the adaptive strategy, multiple PTVs were created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV, cervix, corpus-uterus and upper part of the vagina) and corresponding library plans were generated. Daily CBCTs were rigidly aligned to the full bladder planning CT for plan selection. For daily plan recalculation, selected CTs based on initial similarity were deformably registered to CBCTs. Differences in daily target coverage (D 98%  > 95%) and in V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% for rectum, bladder and bowel were assessed. Non-adaptive RT showed inadequate primary CTV coverage in 17% of the daily fractions. Plan selection compensated for anatomical changes and improved primary CTV coverage significantly (p < 0.01) to 98%. Compared with non-adaptive RT, plan selection decreased the fraction dose to rectum and bowel indicated by significant (p < 0.01) improvements for daily V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% . However, daily plan selection significantly increased the bladder V 1.5Gy , V 2Gy , D 50% and D 2% . In cervical cancer RT, a non-adaptive strategy led to inadequate target coverage for individual patients. Daily plan selection corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to bowel and rectum was decreased significantly when applying adaptive RT.

Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin.

PubMed

Ahmad, Hesham M

2015-01-01

Acne vulgaris is a debilitating disorder and requires proper treatment. This work evaluates the clinical efficacy, side effects, and laboratory changes of serum lipids and liver function during oral isotretinoin therapy for acne vulgaris, comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris were included and randomized into group I (26 patients), who received once daily dose, and group II (32 patients), who received twice daily dose of oral isotretinoin. Global acne scoring system was used to evaluate acne severity and post-treatment improvement. Both regimens resulted in highly significant clinical improvement of acne with no significant difference. However, side effects were significantly more common among patients of group I. Both regimens caused mild rise of serum cholesterol, alanine transaminase (ALT), and aspartate aminotransferase (AST) with more prominent rise of triglycerides especially with twice daily dose. Oral isotretinoin is a very effective treatment for acne vulgaris with no statistically significant difference in clinical efficacy between once and twice daily doses. However, dividing dose to twice per day might cause fewer incidence of side effects without reducing clinical efficacy. The drug causes mild clinically insignificant rise of serum cholesterol, triglycerides, AST, and ALT. © 2015 Wiley Periodicals, Inc.

Andrographis paniculata Extract (HMPL-004) for Active Ulcerative Colitis

PubMed Central

Sandborn, William J; Targan, Stephan R; Byers, Vera S; Rutty, Dean A; Mu, Hua; Zhang, Xun; Tang, Tom

2013-01-01

OBJECTIVES: Andrographis paniculata has in vitro inhibitory activity against TNF-α, IL-1β and NF-κB. A pilot study of A. paniculata extract (HMPL-004) suggested similar efficacy to mesalamine for ulcerative colitis. METHODS: A randomized, double-blind, placebo-controlled trial evaluated the efficacy of A. paniculata extract (HMPL-004) in 224 adults with mild-to-moderate ulcerative colitis. Patients were randomized to A. paniculata extract (HMPL-004) 1,200 mg or 1,800 mg daily or placebo for 8 weeks. RESULTS: In total, 45 and 60% of patients receiving A. paniculata 1,200 mg and 1,800 mg daily, respectively, were in clinical response at week 8, compared with 40% of those who received placebo (P=0.5924 for 1,200 mg vs. placebo and P=0.0183 for 1,800 mg vs. placebo). In all, 34 and 38% of patients receiving A. paniculata 1,200 mg and 1,800 mg daily, respectively, were in clinical remission at week 8, compared with 25% of those who received placebo (P=0.2582 for 1,200 mg vs. placebo and P=0.1011 for 1,800 mg vs. placebo). Adverse events developed in 60 and 53% of patients in the A. paniculata 1,200 mg and 1,800 mg daily groups, respectively, and 60% in the placebo group. CONCLUSIONS: Patients with mildly to moderately active ulcerative colitis treated with A. paniculata extract (HMPL-004) at a dose of 1,800 mg daily were more likely to achieve clinical response than those receiving placebo. PMID:23044768

Predictors for living at home after geriatric inpatient rehabilitation: A prospective cohort study.

PubMed

Kool, Jan; Oesch, Peter; Bachmann, Stefan

2017-01-31

To evaluate patient characteristics predicting living at home after geriatric rehabilitation. Prospective cohort study. A total of 210 patients aged 65 years or older receiving inpatient rehabilitation. Candidate predictors evaluated during rehabilitation were: age, vulnerability (Vulnerable Elders Survey), multimorbidity (Cumulative Illness Rating Scale), cognition (Mini-Mental State Examination), depression (Hospital Anxiety and Depression Scale), living alone, previous independence in activities of daily living, fall risk, and mobility at discharge (Timed Up and Go test). Multiple imputation data-sets, bivariate and multiple regression were used to build a predictive model for living at home, which was evaluated at 3-month follow-up. A total of 210 patients (mean age 76.0 years, 46.2% women) were included in the study. Of these, 87.6% had been admitted to geriatric rehabilitation directly from acute hospital care. Follow-up was complete in 75.2% of patients. The strongest predictor for living at home was better mobility at discharge (Timed Up and Go test < 20 s), followed by lower multimorbidity, better cognition, and not living alone. In bivariate regression, living at home was also associated with age, fall risk, vulnerability, depression, and previous independence in activities of daily living. Mobility is the most important predictive factor for living at home after geriatric rehabilitation. Assessment and training of mobility are therefore key aspects in geriatric rehabilitation.

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in the creatinine clearance in the elderly men and women. Delafloxacin was well tolerated at the tested doses, with gastrointestinal adverse effects observed more commonly at doses ≥1200 mg. Delafloxacin exhibits linear pharmacokinetic parameters that reached steady state after 3 days of daily oral dosing with minimal accumulation. Delafloxacin was well tolerated throughout both studies, with gastrointestinal effects observed at the higher doses (≥1200 mg). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Quetiapine for sleep in patients with dementia.

PubMed

Dolder, Christian R; McKinsey, Jonathan

2010-10-01

to examine the use of quetiapine for sleep in patients with dementia admitted to a geriatric psychiatry ward. retrospective cross-sectional study (January 2007 to December 2009). geriatric psychiatric unit located near a metropolitan city in North Carolina. all patients admitted with a diagnosis of dementia who were also receiving quetiapine were eligible. One hundred one patients met the criteria and were included in the study. none. descriptive statistics defining quetiapine prescribing. Based on a priori criteria, quetiapine was considered to be used for sleep if it were prescribed: 1) only at bedtime, as needed, for sleep, 2) once daily, only at bedtime, or 3) multiple times daily, but with at least 75% of the daily dose administered at bedtime. forty-three of the 101 patients included in the study were prescribed quetiapine, probably for sleep. Quetiapine, when used as a sedative-hypnotic, was generally employed at doses between 50 mg and 100 mg nightly. Several published studies report beneficial sleep-promoting effects of quetiapine and other atypical antipsychotics for primary and secondary sleep complaints; however, most of these trials involve young and middle-aged adults, have diagnostic variability, and are limited methodologically. quetiapine prescribed as a sedative-hypnotic in patients with dementia, while common, is understudied and not without risk.

Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice

PubMed Central

Almenar Cubells, D; Bosch Roig, C; Jiménez Orozco, E; Álvarez, R; Cuervo, JM; Díaz Fernández, N; Sánchez Heras, AB; Galán Brotons, A; Giner Marco, V; Codes M De Villena, M

2013-01-01

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004–2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2–11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1–8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7–5.4) and higher response rate (OR: 2.1, 95%CI: 1.2–3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice. PMID:23331323

Utility of the PFA-100 instrument and the novel multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease.

PubMed

Mueller, Thomas; Dieplinger, Benjamin; Poelz, Werner; Haltmayer, Meinhard

2009-12-01

This study evaluated the utility of the PFA-100 and the Multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease. Platelet function was determined with the PFA-100 using collagen+epinephrine (CEPI) and collagen+adenosine-5'-diphosphate (CADP) cartridges, and with whole blood impedance aggregometry using the Multiplate ASPI and ADP+PG tests (aggregation triggered with arachidonic acid and ADP+ prostaglandin E1, respectively). Four study groups were identified from the 154 patients enrolled: patients without antiplatelet therapy, patients with 100 mg aspirin daily but without clopidogrel treatment, patients with 75 mg clopidogrel daily but without aspirin treatment, and patients with both 100 mg aspirin daily plus 75 mg clopidogrel daily. It was found that the PFA-100 instrument is useful for detection of aspirin but not for detection of a clopidogrel effect, while the Multiplate analyzer is useful for specific detection of both aspirin and clopidogrel effects on platelet function.

Helping motivation and well-being of chronic pain couples: a daily diary study.

PubMed

Kindt, Sara; Vansteenkiste, Maarten; Loeys, Tom; Goubert, Liesbet

2016-07-01

Receiving support from a romantic partner may yield benefits for individuals with chronic pain (ICPs), but may also carry unintended side effects. The conditions under which partner support provision yields (mal)adaptive effects deserve greater attention. Grounded in Self-determination theory, partners may provide help for autonomous or volitional (eg, enjoyment, full commitment) or rather controlled or pressured (eg, avoiding guilt and criticism) motives. This study examined associations between day-to-day fluctuations in partners' type of helping motivation and several outcomes, among partners and ICPs. Seventy couples, with 1 partner having chronic pain (75.7% female), completed a diary for 14 consecutive days. Daily helping motivation was assessed together with daily affect, relational conflict, and relationship-based need satisfaction. Partners (Mage = 55.14) additionally reported on daily helping exhaustion, whereas ICPs (Mage = 54.71) reported on daily pain intensity, disability, satisfaction with received help, and amount of received help. Providing autonomous help related to improvements in partners' affective (eg, positive affect), relational (eg, conflict), and help-specific (eg, exhaustion) functioning, which were accounted for by improvements in daily relationship-based psychological need satisfaction. Similarly, daily autonomously motivated help yielded a direct (ie, relational conflict; perceived amount of help) or indirect (ie, positive and negative affects; relational conflict; satisfaction with help, disability) contribution in explaining ICP outcomes-through improvements in ICPs' relationship-based psychological need satisfaction. Findings highlight the importance of a motivational and dynamic perspective on help provision within chronic pain couples. Considering reasons why a partner provides help is important to understand when partners and ICPs may benefit from daily support.

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice‐daily basal insulin to once‐daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis)

PubMed Central

d'Emden, Michael C.; Fisher, Miles; Ampudia‐Blasco, F. Javier; Stella, Peter; Bizet, Florence; Cali, Anna M. G.; Wysham, Carol H.

2017-01-01

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla‐300) and glargine 100 U/mL (Gla‐100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice‐daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice‐daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla‐300 or Gla‐100 (least squares mean difference −0.01%; 95% confidence interval [CI] −0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI −0.25 to 0.57, in EDITION 2). Participants previously receiving twice‐daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla‐300 vs Gla‐100 at night (00:00–05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla‐300 provided similar glycaemic control with less hypoglycaemia compared with Gla‐100 in people with T2DM switching from twice‐daily to once‐daily basal insulin. PMID:28736942

Acceptability Among Community Healthcare Nurses of Intelligent Wireless Sensor-system Technology for the Rapid Detection of Health Issues in Home-dwelling Older Adults

PubMed Central

Cohen, Christine; Kampel, Thomas; Verloo, Henk

2017-01-01

Background: The effective care and support of community healthcare nurses (CHNs) contribute greatly to the healthy aging of older adults living at home. Integrating innovative technologies into CHNs’ daily practice offers new opportunities and perspectives for early detection of health issues and interventions among home-dwelling older adults. Aim: To explore the perception of acceptability among CHNs of an intelligent wireless sensor system (IWSS) for use in daily practice for the detection of health issues in home-dwelling older adults receiving home healthcare. Method: Descriptive and qualitative data were sourced from a pilot randomized controlled trial involving 17 CHNs using an IWSS in their daily practice to rapidly detect falls and other health issues in patients’ homes. IWSS alerts indicating behavior changes were sent to CHNs. Their perceived usefulness (PU) and perceived ease of use (PEOU) were assessed. The acceptability of IWSS technology was explored using a questionnaire and focus group discussions. Results: The PU and PEOU of the IWSS technology were low to moderate. A majority of the CHNs were dissatisfied with its performance and intrusiveness; they reported multiple obstacles in the usefulness and ease of use of the IWSS technology in daily practice. Conclusion: To improve the IWSS technology’s low to moderate acceptability among CHNs, we recommend a more user-centered implementation strategy and an embedded model of nursing care. PMID:28567170

Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: a systematic review and meta-analysis.

PubMed

Benkhadra, Khalid; Alahdab, Fares; Tamhane, Shrikant U; McCoy, Rozalina G; Prokop, Larry J; Murad, Mohammad Hassan

2017-01-01

The relative efficacy of continuous subcutaneous insulin infusion and multiple daily injections in individuals with type 1 diabetes is unclear. We sought to synthesize the existing evidence about the effect of continuous subcutaneous insulin infusion on glycosylated hemoglobin, hypoglycemic events, and time spent in hypoglycemia compared to multiple daily injections. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus from January 2008 through November 2015 for randomized controlled trials that enrolled children or adults with type 1 diabetes. Trials identified in a previous systematic review and published prior to 2008 were also included. We included 25 randomized controlled trials at moderate risk of bias. Meta-analysis showed a significant reduction in glycosylated hemoglobin in patients treated with continuous subcutaneous insulin infusion compared to multiple daily injections (mean difference 0.37; 95 % confidence interval, 0.24-0.51). This effect was demonstrated in both children and adults. There was no significant difference in minor or severe hypoglycemic events. Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia. There was no significant difference in the time spent in hypoglycemia. In children and adults with type 1 diabetes and compared to multiple daily injections, continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin. There was no difference in severe or minor hypoglycemia, but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion.

Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma.

PubMed

Kumar, Shaji; Kaufman, Jonathan L; Gasparetto, Cristina; Mikhael, Joseph; Vij, Ravi; Pegourie, Brigitte; Benboubker, Lofti; Facon, Thierry; Amiot, Martine; Moreau, Philippe; Punnoose, Elizabeth A; Alzate, Stefanie; Dunbar, Martin; Xu, Tu; Agarwal, Suresh K; Enschede, Sari Heitner; Leverson, Joel D; Ross, Jeremy A; Maciag, Paulo C; Verdugo, Maria; Touzeau, Cyrille

2017-11-30

Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in multiple myeloma (MM) cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-X L and MCL-1. In this phase 1 study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added on progression during treatment. Sixty-six patients were enrolled (30, dose-escalation cohorts; 36, safety expansion). Patients received a median of 5 prior therapies (range, 1-15); 61% were bortezomib and lenalidomide double refractory, and 46% had t(11;14). Venetoclax was generally well tolerated. Most common adverse events included mild gastrointestinal symptoms (nausea [47%], diarrhea [36%], vomiting [21%]). Cytopenias were the most common grade 3/4 events, with thrombocytopenia (32%), neutropenia (27%), anemia (23%), and leukopenia (23%) reported. The overall response rate (ORR) was 21% (14/66), and 15% achieved very good partial response or better (≥VGPR). Most responses (12/14 [86%]) were reported in patients with t(11;14). In this group, ORR was 40%, with 27% of patients achieving ≥VGPR. Biomarker analysis confirmed that response to venetoclax correlated with higher BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios. Venetoclax monotherapy at a daily dose up to 1200 mg has an acceptable safety profile and evidence of single-agent antimyeloma activity in patients with relapsed/refractory MM, predominantly in patients with t(11;14) abnormality and those with a favorable BCL2 family profile. Registered at www.clinicaltrials.gov: #NCT01794520. © 2017 by The American Society of Hematology.

Significant partial response of metastatic intra-abdominal and pelvic round cell liposarcoma to a small-molecule VEGFR-2 tyrosine kinase inhibitor apatinib: A case report.

PubMed

Dong, Min; Bi, Jingwang; Liu, Xiaohong; Wang, Baocheng; Wang, Jun

2016-08-01

Myxoid/round cell liposarcoma is the second most common subtype of liposarcoma. Chemotherapy and radiotherapy have a limited efficacy for treating advanced myxoid/round cell liposarcoma, with relatively serious side effects. We herein present a 68-year-old Chinese woman initially diagnosed with advanced multiple intra-abdominal and pelvic round cell liposarcoma.She refused to receive cytotoxic chemotherapy and received apatinib as the first-line therapy, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 that has been used in the treatment of patients with metastatic gastric cancer who progressed with 2 or more chemotherapy regimens. This patient was partially responsive to apatinib with a dose of 500 mg daily. No serious drug-related side effects were observed. Our findings indicate that some cases of liposarcoma may be responsive to antiangiogenic agent apatinib. Randomized clinical studies are needed to further confirm the efficacy and safety of apatinib in the clinical treatment of liposarcoma.

Prevention of Incontinence Associated Skin Damage in Nursing Homes: Disparities and Predictors

PubMed Central

Bliss, Donna Z.; Gurvich, Olga V.; Mathiason, Michelle A.; Eberly, Lynn E.; Savik, Kay; Harms, Susan; Mueller, Christine; Wyman, Jean F.; Virnig, Beth

2016-01-01

Racial/ethnic disparities in preventing health problems have been reported in nursing homes. Incontinence is common among nursing home residents and can result in inflammatory-type skin damage, referred to as incontinence associated skin damage (IASD). Little is known about the prevention of IASD and whether there are racial/ethnic disparities in its prevention. This study assessed the proportion of older nursing home residents receiving IASD prevention after developing incontinence after admission (n=10,713) and whether there were racial/ethnic disparities in IASD prevention. Predictors of preventing IASD were also examined. Four national datasets provided potential predictors at multiple levels. Disparities were analyzed using the Peters-Belson method; predictors of preventing IASD were assessed using hierarchical logistic regression. Prevention of IASD was received by 0.12 of residents and no racial/ethnic disparities were found. Predictors of preventing IASD were primarily resident level factors including limitations in activities of daily living, poor nutrition, and more oxygenation problems. PMID:27586441

ADHERENCE TO ANTIRETROVIRAL THERAPY AMONG HIV-INFECTED ADULTS IN THE UNITED STATES

PubMed Central

Beer, Linda; Skarbinski, Jacek

2015-01-01

National estimates of antiretroviral therapy (ART) adherence and adherence support services utilization are needed to inform efforts to improve the health of HIV-infected persons in the United States. In a nationally representative sample of HIV-infected adults receiving medical care, 86% self-reported taking all ART doses in the past 72 hours. Overall, 20% reported using adherence support services and 2% reported an unmet need for services. If all nonadherent persons not receiving adherence support and all persons with a self-perceived unmet need for adherence support accessed services, resources to support ~42,673 additional persons would be needed. Factors associated with lower adherence included younger age, female gender, depression, stimulant use, binge alcohol use, greater than once-daily dosing, longer time since HIV diagnosis, and patient beliefs. Predictors of adherence are multifactorial so multiple targeted strategies to improve adherence are warranted. Providing adherence support services to all those in need may require additional resources. PMID:25490733

Use of Accelerometer-Based Feedback of Walking Activity for Appraising Progress With Walking-Related Goals in Inpatient Stroke Rehabilitation: A Randomized Controlled Trial.

PubMed

Mansfield, Avril; Wong, Jennifer S; Bryce, Jessica; Brunton, Karen; Inness, Elizabeth L; Knorr, Svetlana; Jones, Simon; Taati, Babak; McIlroy, William E

2015-10-01

Regaining independent ambulation is important to those with stroke. Increased walking practice during "down time" in rehabilitation could improve walking function for individuals with stroke. To determine the effect of providing physiotherapists with accelerometer-based feedback on patient activity and walking-related goals during inpatient stroke rehabilitation. Participants with stroke wore accelerometers around both ankles every weekday during inpatient rehabilitation. Participants were randomly assigned to receive daily feedback about walking activity via their physiotherapists (n = 29) or to receive no feedback (n = 28). Changes in measures of daily walking (walking time, number of steps, average cadence, longest bout duration, and number of "long" walking bouts) and changes in gait control and function assessed in-laboratory were compared between groups. There was no significant increase in walking time, number of steps, longest bout duration, or number of long walking bouts for the feedback group compared with the control group (P values > .20). However, individuals who received feedback significantly increased cadence of daily walking more than the control group (P = .013). From the in-laboratory gait assessment, individuals who received feedback had a greater increase in walking speed and decrease in step time variability than the control group (P values < .030). Feedback did not increase the amount of walking completed by individuals with stroke. However, there was a significant increase in cadence, indicating that intensity of daily walking was greater for those who received feedback than the control group. Additionally, more intense daily walking activity appeared to translate to greater improvements in walking speed. © The Author(s) 2015.

Very early social support following mild stroke is associated with emotional and behavioral outcomes three months later.

PubMed

Villain, Marie; Sibon, Igor; Renou, Pauline; Poli, Mathilde; Swendsen, Joel

2017-01-01

To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later. Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24 hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later. A university hospital acute stroke unit. Thirty-four mild ischemic stroke patients. None. One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework. The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels ( p = 0.041) and increases in activities of daily living ( p = 0.011). Material support from friends and family was associated with increases in activities of daily living ( p = 0.012). No effect was observed for support received from medical staff. Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later.

Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA).

PubMed

Stone, Adam F M; Mendall, Michael A; Kaski, Juan-Carlos; Edger, Tracey M; Risley, Paul; Poloniecki, Jan; Camm, A John; Northfield, Timothy C

2002-09-03

Infection with Helicobacter pylori and Chlamydia pneumoniae is associated with coronary heart disease. We conducted an intervention study using antibiotics against these bacteria in patients with acute coronary syndromes to determine whether antibiotics reduce inflammatory markers and adverse cardiac events. Patients (n=325) admitted with acute myocardial infarction or unstable angina (acute coronary syndromes) were randomized to receive a 1-week course of 1 of 3 treatment regimens: (1) placebo; (2) amoxicillin (500 mg twice daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily); or (3) azithromycin (500 mg once daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily). Serum fibrinogen, white cell count, and high-sensitivity C-reactive protein were measured at study entry and at 1, 3, and 12 months during follow-up. Cardiac death and readmission with acute coronary syndrome were considered clinical end points. Patients were followed for 1 year. C-reactive protein levels were reduced (P=0.03) in unstable angina patients receiving amoxicillin, and fibrinogen was reduced in both patient groups receiving antibiotics (P=0.06). There were 17 cardiac deaths and 71 readmissions with acute coronary syndrome. No difference in frequency or timing of end points was observed between the 2 antibiotic groups. At 12 weeks, there was a 36% reduction in all end points in patients receiving antibiotics compared with placebo (P=0.02). This reduction persisted during the 1-year follow-up. Neither C pneumoniae nor H pylori antibody status was significantly related to response to treatment. Antibiotic treatment significantly reduced adverse cardiac events in patients with acute coronary syndromes, but the effect was independent of H pylori or C pneumoniae seropositivity.

Long-term care planning and preparation among persons with multiple sclerosis.

PubMed

Putnam, Michelle; Tang, Fengyan

2008-01-01

Individuals with multiple sclerosis (MS) primarily rely on informal supports such as family members and assistive technology to meet their daily needs. As they age, formal supports may become important to compliment these supports and sustain community-based living. No previous research exists exploring plans and preparations of persons with MS for future independent living and long-term care needs. We analyzed data from a random sample survey (N = 580) to assess knowledge and perceptions of future service needs using ANOVA, chi-square, correlations, and MANOVA procedures. Results indicate that overall, most respondents are not well informed and have not planned or prepared for future care needs. Persons reporting severe MS were more likely to plan and prepare. Key "entry points" for making preparations include receiving specific education and planning information, discussions with family and professional service providers, and increased age, education, and income. We recommend greater infusion of long-term care planning into these existing entry points and creation of new entry points including healthcare provides and insurers.

Gait and Glasgow Coma Scale scores can predict functional recovery in patients with traumatic brain injury☆

PubMed Central

Bilgin, Sevil; Guclu-Gunduz, Arzu; Oruckaptan, Hakan; Kose, Nezire; Celik, Bülent

2012-01-01

Fifty-one patients with mild (n = 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score. Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury. PMID:25624828

Comparison of Levetiracetam Dosing Regimens in End-Stage Renal Disease Patients Undergoing Intermittent Hemodialysis.

PubMed

Shiue, Harn J; Taylor, Maria; Sands, Kara A

2017-10-01

Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels. To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD. Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses. We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group. Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis).

PubMed

Roussel, Ronan; d'Emden, Michael C; Fisher, Miles; Ampudia-Blasco, F Javier; Stella, Peter; Bizet, Florence; Cali, Anna M G; Wysham, Carol H

2018-02-01

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Clarithromycin vs. Gemifloxacin in Quadruple Therapy Regimens for Empiric Primary Treatment of Helicobacter pylori Infection: A Randomized Clinical Trial

PubMed Central

Masoodi, Mohsen; Talebi-Taher, Mahshid; Tabatabaie, Khadijeh; Khaleghi, Siamak; Faghihi, Amir-Hossein; Agah, Shahram; Asadi, Reyhaneh

2015-01-01

BACKGROUND Eradication of Helicobacter pylori infection plays a crucial role in the treatment of peptic ulcer. Clarithromycin resistance is a major cause of treatment failure. This randomized clinical trial aimed at evaluating the efficacy of a clarithromycin versus gemifloxacin containing quadruple therapy regimen in eradication of H.pylori infection. METHODS In this randomized double blind clinical trial (RCT 2012102011054N2), a total of 120 patients were randomized to two groups of 60 patients each. Patients with proven H.pylori infection were consecutively assigned into two groups to receive OBAG or OBAC in gastroenterology clinic in Rasoul-e- Akram General Hospital in Tehran, Iran. The patients in the OBAG group received omeprazole (20 mg) twice daily, bismuth subcitrate (240 mg) twice daily, amoxicillin (1 gr) twice daily, and gemifloxacin (320 mg) once daily, and those in the OBAC group received omeprazole (20 mg) twice daily, 240 mg of bismuth subcitrate twice daily, amoxicillin (1 gr) twice daily, and clarithromycin (500 mg) twice daily for 10 days. RESULTS Five patients from each group were excluded from the study because of poor compliance, so 110 patients completed the study. The intention-to-treat eradication rate was 61.6% and 66.6% for the OBAC and OBAG groups, respectively. According to the per protocol analysis, the success rates of eradication of H.pylori infection were 67.2% and 72.7% for OBAC and OBAG groups, respectively (p=0.568). CONCLUSION The results of this study suggest that gemifloxacin containing regimen is at least as effective as clarithromycin regimen; hence, this new treatment could be considered as an alternative for the patients who cannot tolerate clarithromycin. PMID:26106468

Helping Your Partner with Chronic Pain: The Importance of Helping Motivation, Received Social Support, and Its Timeliness.

PubMed

Kindt, Sara; Vansteenkiste, Maarten; Josephy, Haeike; Bernardes, Sonia F; Goubert, Liesbet

2018-02-02

Like all intentional acts, social support provision varies with respect to its underlying motives. Greater autonomous or volitional motives (e.g., enjoyment, full commitment) to help individuals with chronic pain (ICPs) are associated with greater well-being benefits for the latter, as indexed by improved satisfaction of their psychological needs for autonomy, competence, and relatedness. The present study investigates the processes explaining why partners' autonomous or volitional helping motivation yields these benefits. A total of 134 couples, where at least one partner had chronic pain, completed a 14-day diary. Partners reported on their daily helping motives, whereas ICPs reported on their daily received support, timing of help, need-based experiences, and pain. On days when partners provided help for volitional motives, ICPs indicated receiving more help, which partially accounted for the effect of autonomous helping motivation on ICP need-based experiences. Timing of help moderated the effects of daily received support on ICP need-based experiences. Findings highlight the importance of ICPs of receiving support in general and the role of timing in particular, which especially matters when there is little support being received. © 2018 American Academy of Pain Medicine. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study.

PubMed

Son, Mijeong; Guk, Jinju; Kim, Yukyung; Woo Chae, Dong; Heo, Young-A; Soh, Dongjun; Park, Kyungsoo

2016-08-01

Rosuvastatin, a hydroxy methylglutaryl coenzyme A reductase inhibitor; telmisartan, an angiotensin receptor blocker; and amlodipine, a calcium channel inhibitor, are commonly prescribed together for the treatment of hypertension nonresponsive to monotherapy and accompanied by dyslipidemia. However, the pharmacokinetic interactions among these 3 substances are not well understood. The aim of this study was to investigate the pharmacokinetic drug-drug interactions among rosuvastatin, telmisartan, and amlodipine in a healthy Korean male population. In both parts of this randomized, open-label, multiple-dose, 2-part, 2-period crossover study, subjects aged 19 to 55 years were enrolled. In part 1, each subject received rosuvastatin 20 mg with and without 2 fixed-dose combination (FDC) tablets of telmisartan/amlodipine 40/5 mg, once daily for 9 consecutive days. In part 2, each subject received 2 FDC tablets of telmisartan/amlodipine 40/5 mg with and without rosuvastatin 20 mg, once daily for 9 consecutive days. In both parts, there was a 13-day washout period between treatments. Pharmacokinetic samples were collected up to 72 hours after the last dose in subjects who received rosuvastatin only, and up to 144 hours after the last dose in subjects who received telmisartan/amlodipine with or without rosuvastatin. Adverse events (AEs) were assessed via interviews and physical examinations. Forty-eight subjects were enrolled, of whom 19 in part 1 and 22 in part 2 completed the study. In Part 1, the 90% CIs of the geometric mean ratios (GMRs) (coadministration of rosuvastatin and telmisartan/amlodipine to monotherapy with rosuvastatin) of the primary pharmacokinetic parameters (AUCτ and Cmax,ss) were: rosuvastatin, 1.1436 to 1.3059 and 1.8970 to 2.3514, respectively; and N-desmethyl rosuvastatin, 0.8441 to 1.0200 and 1.1971 to 1.5457. In part 2, the 90% CIs of the GMRs (coadministration to monotherapy with telmisartan/amlodipine) were: telmisartan, 1.1204 to 1.4228 and 0.9940 to 1.5940; amlodipine, 0.9705 to 1.0636 and 0.9813 to 1.0779. There were no significant differences in the prevalences of AEs between the treatments, and all reported AEs were mild or moderate. These results demonstrate that when rosuvastatin, telmisartan, and amlodipine are coadministered to healthy male subjects, pharmacokinetic exposure increases with respect to rosuvastatin and telmisartan, whereas no change occurs with respect to amlodipine. However, based on previous analyses, the degree of increase in the exposure observed was not regarded as clinically significant. All treatments were well-tolerated. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Stability and Change in Sustainability of Daily Routines and Social Networks in Families of Children with Profound Intellectual and Multiple Disabilities

ERIC Educational Resources Information Center

Wilder, Jenny; Granlund, Mats

2015-01-01

Background: Children with profound intellectual and multiple disabilities (PIMD) demand intense family accommodations from birth and onwards. This study used an exploratory and qualitative study design to investigate stability and change in sustainability of daily routines and social networks of Swedish families of children with PIMD. Materials…

Pharmacodynamic Effects of Single and Multiple Doses of Empagliflozin in Patients With Type 2 Diabetes.

PubMed

Heise, Tim; Jordan, Jens; Wanner, Christoph; Heer, Martina; Macha, Sreeraj; Mattheus, Michaela; Lund, Søren S; Woerle, Hans J; Broedl, Uli C

2016-10-01

Our aim was to investigate the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin on urinary and serum glucose and electrolytes, urinary volume, osmolality, and the renin-angiotensin system in patients with type 2 diabetes. In an open-label study, 22 patients receiving metformin (median age 56 years; range 40-65 years) received empagliflozin 25 mg once daily for 5 days. Food, fluid, and sodium intake were standardized for 3 days before and during treatment. Twenty patients completed treatment. After single and multiple doses of empagliflozin, mean (SE) changes from baseline in 24-hour urinary glucose excretion were 463.3 (57.3) mmol/d and 599.5 (60.0) mmol/d, respectively (83.5 [10.3] g/d and 108.0 [10.8] g/d, respectively) (both P < 0.001), and in fasting serum glucose concentration were -1.8 (0.4) mmol/L and -1.1 (0.3) mmol/L, respectively (both P < 0.001). After a single dose, mean (SE) change from baseline in urine sodium excretion was 45.3 (9.6) mmol/d (P < 0.001), and in urine volume was 341.0 (140.5) g/d (P = 0.025), but there were no changes compared with baseline in either parameter after multiple doses. There were no changes in plasma renin or serum aldosterone with single or multiple doses of empagliflozin. There was a nonsignificant reduction in weight after a single dose of empagliflozin and a mean (SE) change of -1.4 (0.5) kg after multiple doses (P = 0.020). Empagliflozin 25 mg increased urinary glucose excretion and decreased serum glucose and weight with transient natriuresis and increases in urine volume, without significant changes in the renin-angiotensin system. Clinicaltrials.gov Identifier: NCT01276288. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Efficacy and tolerability of rasagiline in daily clinical use--a post-marketing observational study in patients with Parkinson's disease.

PubMed

Reichmann, H; Jost, W H

2010-09-01

The MAO-B inhibitor rasagiline is indicated for the treatment of idiopathic Parkinson's disease (PD), and its use is supported by evidence from large-scale, controlled clinical studies. The post-marketing observational study presented here investigated the efficacy and tolerability of rasagiline treatment (monotherapy or combination therapy) in daily clinical practice. The study included patients with idiopathic PD who received rasagiline (recommended dose 1 mg, once daily) as monotherapy or combination therapy. The treatment and observation period was approximately 4 months. Outcome measures included the change from baseline in the Columbia University Rating Scale (CURS), the Unified PD Rating Scale fluctuation subscale, daily OFF time (patient home diaries) and the PD Questionnaire-39. Adverse drug reactions/adverse events (ADRs/AEs) and the physician's global judgement of tolerability and efficacy were also examined. Overall, 754 patients received rasagiline during the study. Patients treated with rasagiline (monotherapy or combination therapy) showed significant improvements from baseline in symptom severity (including classical motor and non-classical motor/non-motor symptoms) and quality of life (QoL). Patients receiving combination therapy also experienced significant reductions in daily OFF time. Tolerability was rated as good/very good in over 90% of patients. In daily clinical practice, monotherapy or combination therapy with rasagiline is able to improve PD symptoms, reduce OFF time, and improve QoL, whilst demonstrating favourable tolerability. In addition, rasagiline has a simple dosing schedule of one tablet, once daily, with no titration. These results are consistent with the pivotal rasagiline clinical studies (TEMPO, LARGO and PRESTO).

Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis.

PubMed

Fox, Robert J; Miller, David H; Phillips, J Theodore; Hutchinson, Michael; Havrdova, Eva; Kita, Mariko; Yang, Minhua; Raghupathi, Kartik; Novas, Mark; Sweetser, Marianne T; Viglietta, Vissia; Dawson, Katherine T

2012-09-20

BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing-remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate). In this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing-remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The study was not designed to test the superiority or noninferiority of BG-12 versus glatiramer acetate. At 2 years, the annualized relapse rate was significantly lower with twice-daily BG-12 (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice-daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate significantly reduced the numbers of new or enlarging T(2)-weighted hyperintense lesions (all P<0.001) and new T(1)-weighted hypointense lesions (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12 versus glatiramer acetate, differences were not significant except for the annualized relapse rate (thrice-daily BG-12), new or enlarging T(2)-weighted hyperintense lesions (both BG-12 doses), and new T(1)-weighted hypointense lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events (with BG-12) and injection-related events (with glatiramer acetate). There were no malignant neoplasms or opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG-12. In patients with relapsing-remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.).

Effect of micronutrient supplement on health and nutritional status of schoolchildren: biochemical status.

PubMed

Sivakumar, Battiprolu; Nair, Krishnapillai Madhavan; Sreeramulu, Dande; Suryanarayana, Palla; Ravinder, Punjal; Shatrugna, Veena; Kumar, Prattipati Ajey; Raghunath, Manchala; Rao, Varaganti Vikas; Balakrishna, Nagalla; Kumar, Putcha Uday; Raghuramulu, Namala

2006-01-01

We assessed the effect of a daily intake of a micronutrient-fortified beverage for 14 mo on indicators of biochemical status of important micronutrients in schoolchildren. A double-blind, placebo-controlled, matched-pair, cluster, randomization study design was used. Biochemical indicators of micronutrient status were evaluated at baseline and at the end of 14 mo on a subsample in nine matched pairs. Prevalence (percentage) of subclinical deficiency, mean, and mean increments of each indicator were compared between supplemented and placebo groups. Extent of inadequacy at baseline was more or less 100% for folic acid, 65% for vitamins B2 and B6, and 55% for vitamins C and A. Prevalence of anemia among subjects was 55%, with inadequacy of vitamin B12 being 40% and that of vitamin D being 30%. No subject had inadequacy of iodine based on urinary iodine. Supplementation of a micronutrient-enriched beverage for 14 mo significantly improved the status of many of the nutrients. The effect was significant with respect to vitamins A, B2, and B12, folic acid, vitamin D, parathyroid hormone, and thyroid-stimulating hormone in children who received the supplement compared with those who received only placebo. Hemoglobin status improved only in children who had anemia in the supplemented group. Prevalence of multiple subclinical micronutrient deficiencies are high in middle-income Indian school children. Daily consumption of a micronutrient-enriched beverage had positive effects that were confined to those nutrients that were inadequate at baseline.

Neighborhood support network, perceived proximity to community facilities and depressive symptoms among low socioeconomic status Chinese elders.

PubMed

Chen, Yan-Yan; Wong, Gloria H Y; Lum, Terry Y; Lou, Vivian W Q; Ho, Andy H Y; Luo, Hao; Tong, Tracy L W

2016-01-01

Depressive symptoms are common in older people; most previous research on elderly depression focused on individual-level characteristics or neighborhood socioeconomic status. Modifiable neighborhood characteristics of older people dwelling in low-income communities are under-studied. This study aims to identify potentially modifiable social and physical neighborhood characteristics that influence depressive symptoms independent of individual-level characteristics among older Chinese. Data came from a cross-sectional survey conducted in four low-income public rental housing estates in Hong Kong in 2012. We interviewed a total of 400 elderly residents. The structured questionnaire covered demographics, activities of daily living, recent fall history, neighborhood support networks, and perceived proximity by walk to community facilities. Multiple regression was used to test whether inclusion of neighborhood factors in addition to individual characteristics increases model fit in explaining depressive symptoms in elders with low socioeconomic status. At individual level, activities of daily living and income significantly predicted depressive symptoms. Receiving support from friends or neighbors is associated with fewer depressive symptoms. However, participants who received organizational support had a 1.17 points of increase on the 15-item Geriatric Depression Scale (GDS-15). At-ease walkable proximity to medical facilities was positively associated with a better GDS score. Neighborhood support networks and perceived proximity by walk to community facilities contribute significantly to depressive symptoms among low-income elders. Programs and policies that facilitate neighborhood support and commuting or promote facility accessibility may help ameliorate depressive symptoms common among low-income elders.

Impact of early human milk on sepsis and health-care costs in very low birth weight infants.

PubMed

Patel, A L; Johnson, T J; Engstrom, J L; Fogg, L F; Jegier, B J; Bigger, H R; Meier, P P

2013-07-01

To study the incidence of sepsis and neonatal intensive care unit (NICU) costs as a function of the human milk (HM) dose received during the first 28 days post birth for very low birth weight (VLBW) infants. Prospective cohort study of 175 VLBW infants. The average daily dose of HM (ADDHM) was calculated from daily nutritional data for the first 28 days post birth (ADDHM-Days 1-28). Other covariates associated with sepsis were used to create a propensity score, combining multiple risk factors into a single metric. The mean gestational age and birth weight were 28.1 ± 2.4 weeks and 1087 ± 252 g, respectively. The mean ADDHM-Days 1-28 was 54 ± 39 ml kg(-1) day(-1) (range 0-135). Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days 1-28 was associated with lower odds of sepsis (odds ratio 0.981, 95% confidence interval 0.967-0.995, P=0.008). Increasing ADDHM-Days 1-28 was associated with significantly lower NICU costs. A dose-response relationship was demonstrated between ADDHM-Days 1-28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score. For every HM dose increase of 10 ml kg(-1) day(-1), the odds of sepsis decreased by 19%. NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days 1-28.

Impact of Early Human Milk on Sepsis and Health Care Costs in Very Low Birth Weight Infants

PubMed Central

Patel, Aloka L.; Johnson, Tricia J.; Engstrom, Janet L.; Fogg, Louis F.; Jegier, Briana J.; Bigger, Harold R.; Meier, Paula P.

2013-01-01

Objective To study the incidence of sepsis and neonatal intensive care unit (NICU) costs as a function of the human milk (HM) dose received during the first 28 days post-birth for very low birth weight (VLBW) infants. Study Design Prospective cohort study of 175 VLBW infants. Average daily dose of HM (ADDHM) was calculated from daily nutritional data for the first 28 days post-birth (ADDHM-Days1-28). Other covariates associated with sepsis were used to create a propensity score, combining multiple risk factors into a single metric. Result The mean gestational age and birth weight were 28.1 ± 2.4 wk and 1087 ± 252 g, respectively. The mean ADDHM-Days1-28 was 54 ± 39 mL/kg/d (range 0-135). Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days1-28 was associated with lower odds of sepsis (OR .981, 95%CI .967-.995, p=.008). Increasing ADDHM-Days1-28 was associated with significantly lower NICU costs. Conclusion A dose-response relationship was demonstrated between ADDHM-Days1-28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score. For every HM dose increase of 10 mL/kg/d, the odds of sepsis decreased by 19%. NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days1-28. PMID:23370606

Teaching Reading Comprehension Skills to a Child with Autism Using Behaviour Skills Training.

PubMed

Singh, Binita D; Moore, Dennis W; Furlonger, Brett E; Anderson, Angelika; Busacca, Margherita L; English, Derek L

2017-10-01

A multiple probe design across skills was used to examine the effects of behaviour skills training (BST) on teaching four reading comprehension skills (predicting, questioning, clarifying, and summarizing) to a 7th grade student with autism. Following baseline, the student received 12 sessions of BST during which each skill was taught to criterion. At each session, data was also collected on the accuracy of oral responses to 10 comprehension questions. BST was associated with clear gains in the participant's performance on each comprehension skill, along with concomitant gains in reading comprehension both on the daily probes and a standardized measure. Skills maintained at follow-up support the conclusion that BST was effective in improving the comprehension skills of a child with autism.

How Do Pain, Fatigue, Depressive, and Cognitive Symptoms Relate to Well-Being and Social and Physical Functioning in the Daily Lives of Individuals With Multiple Sclerosis?

PubMed

Kratz, Anna L; Braley, Tiffany J; Foxen-Craft, Emily; Scott, Eric; Murphy, John F; Murphy, Susan L

2017-11-01

To examine the relative association between daily change in pain, fatigue, depressed mood, and cognitive function and 4 outcomes-positive affect and well-being, ability to participate in social roles and activities, upper extremity (UE) functioning, and lower extremity (LE) functioning. Data analysis, multilevel mixed modeling. General community. Ambulatory adults (N=102) with multiple sclerosis. Not applicable. Customized short-forms of the Quality of Life in Neurological Disorders positive affect and well-being, UE functioning, and LE functioning item banks and the Patient-Reported Outcomes Measurement Information System ability to participate in social roles and activities item bank adapted for daily use and administered as end-of-day diaries. Above and beyond the effects of demographic and clinical covariates, daily pain was associated with 3 of the 4 outcomes; days of higher than usual pain were related to lower same-day social participation (unstandardized β, B=-1.00; P=.002), UE functioning (B=-1.04; P=.01), and LE functioning (B=-.71; P=.04). Daily fatigue and depressed mood were independently related to daily positive affect and well-being; days of worse fatigue (B=-.54; P=.006) and depressed mood (B=-1.17; P<.0001) were related to lower same-day well-being. The results indicate the role of fluctuations in symptoms in daily functioning and quality of life of individuals with multiple sclerosis. Daily increases in pain intensity are related to social and physical functioning, whereas increases in fatigue and depressed mood are related to lower daily well-being. Findings implicate a person-centered approach to monitoring and treating symptoms. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The Flying Newsboy: A Small Daily Attempts Air Delivery.

ERIC Educational Resources Information Center

Watts, Elizabeth A.

For 10 months in 1929-30, subscribers to "The McCook (Nebraska) Daily Gazette" (a daily newspaper serving 33 towns in southwestern Nebraska and northwestern Kansas) received their newspapers via air delivery with "The Newsboy," a Curtis Robin cabin monoplane. In an age when over-the-road travel was difficult and air travel was…

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

PubMed

White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

2016-09-22

KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .).

ONCE DAILY RISPERIDONE IN TREATMENT OF SCHIZOPHRENIA

PubMed Central

Agarwal, Vivek; Chadda, Rakesh K.

2001-01-01

Forty four schizophrenic patients were randomly assigned to receive risperidone in 4-8 mg doses either once daily or twice daily for 8 weeks. An open trial was conducted to determine the efficacy of once daily administration of risperidone as compared to twice daily administration. Assessment were done on Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scale Eighty two percent of the once daily patients and 79% of the twice daily patients showed a significant treatment response. No significant differences were observed between the two groups in response pattern and adverse effects at the end point. Risperidone given once daily was as effective as twice daily administration. PMID:21407835

Analysis and Simulation of Disadvantaged Receivers for Multiple-Input Multiple-Output Communications Systems

DTIC Science & Technology

2010-09-01

SIMULATION OF DISADVANTAGED RECEIVERS FOR MULTIPLE-INPUT MULTIPLE- OUTPUT COMMUNICATIONS SYSTEMS by Tracy A. Martin September 2010 Thesis...DATE September 2010 3. REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE Analysis and Simulation of Disadvantaged Receivers...Channel State Information at the Transmitter (CSIT). A disadvantaged receiver is subsequently introduced to the system lacking the optimization enjoyed

Adverse drug reactions and outcome of short course anti-tuberculosis drugs between single daily dose and split drug dose (BID) in pulmonary tuberculosis.

PubMed

Chuchottaworn, Charoen; Saipan, Benjawan; Kittisup, Chomnapa; Cheewakul, Krisana

2012-08-01

Standard six months short course regimen for treatment of pulmonary tuberculosis is very effective and is recommended as standard treatment. But this regimen composes of many drugs and causes high adverse drug reactions especially gastrointestinal irritation. Spitted administration of drugs to two times a day may reduce adverse drug reactions. To study adverse drug reactions and outcome of single daily versus split drug (two times a day) administration of standard six month short course regimen in newly diagnosed pulmonary tuberculosis. Newly diagnosed pulmonary tuberculosis patients of the Central Chest Institute of Thailand were randomized to receive standard six months regimen once daily or two times a day (split drug). Patients were followed-up every two weeks and a questionnaire was used to detect adverse drug reactions. Outcome of treatment was evaluated according to national tuberculosis treatment guideline. 122 pulmonary tuberculosis were eligible for the present study and 61 patients were enrolled to each group of once daily or split drug regimen. Pulmonary tuberculosis patients who received split drug regimen had a higher cure rate but not statistical significance because of lower transfer out rate. Adverse drug reactions were similar in both groups of patients who received once daily and split drug regimen. Although split drug group had lower gastrointestinal adverse drug reactions. Split drug regimen has the same cure rate of treatment as single daily regimen and same adverse drug reactions.

Once-daily MMX(®) mesalamine for endoscopic maintenance of remission of ulcerative colitis.

PubMed

D'Haens, Geert; Sandborn, William J; Barrett, Karen; Hodgson, Ian; Streck, Paul

2012-07-01

Treatment with mesalamine to maintain endoscopic remission (mucosal healing) of ulcerative colitis (UC) has been shown to reduce the risk of relapse and is the recommended first-line maintenance therapy. To improve treatment adherence, a mesalamine formulation that can be administered once-daily, MMX(®) mesalamine (Lialda; Shire Pharmaceuticals LLC, Wayne, PA), was developed. This study was conducted to determine the efficacy and safety of once-daily MMX mesalamine compared with twice-daily delayed-release mesalamine (Asacol; Warner Chilcott, Dublin, Ireland) for maintaining endoscopic remission in patients with UC. A multicenter, randomized, double-blind, 6-month, active-control trial was conducted to assess the non-inferiority of once-daily MMX mesalamine 2.4 g/day compared with twice-daily delayed-release mesalamine at a total daily dose of 1.6 g/day in patients with UC in endoscopic remission. The primary end point was maintenance of endoscopic remission at month 6 in the per-protocol (PP) population. Overall, 826 patients were randomized and dosed. The primary objective (non-inferiority) was met. At month 6, 83.7 and 77.8% of patients receiving MMX mesalamine in the PP and intent-to-treat (ITT) populations, respectively, had maintained endoscopic remission compared with 81.5% (PP) and 76.9% (ITT) of patients receiving delayed-release mesalamine (95% confidence interval for difference: -3.9%, 8.1% (PP); -5.0%, 6.9% (ITT)). Time to relapse was not significantly different between the two treatment groups (log-rank test, P=0.5116 (PP); P=0.5455 (ITT)). The proportion of patients with adverse events was 37.1 and 36.0% in patients receiving MMX mesalamine and delayed-release mesalamine, respectively. Once-daily dosing of MMX mesalamine 2.4 g/day was shown to be well tolerated and non-inferior to twice-daily dosing with delayed-release mesalamine 1.6 g/day for maintenance of endoscopic remission in patients with UC.

Factors influencing the impact of oral health on the daily activities of adolescents, adults and older adults

PubMed Central

Bulgareli, Jaqueline Vilela; de Faria, Eduardo Tanajura; Cortellazzi, Karine Laura; Guerra, Luciane Miranda; Meneghim, Marcelo de Castro; Ambrosano, Glaucia Maria Bovi; Frias, Antonio Carlos; Pereira, Antonio Carlos

2018-01-01

ABSTRACT OBJECTIVE: Analyze if clinical, sociodemographic and access to dental services variables influence the impact of oral health on the daily activities of adolescents, adults and older adults. METHODS: A cross-sectional study with secondary data from the State Oral Health Survey (SB São Paulo 2015) conducted in 163 cities of São Paulo. A total of 17,560 individuals from three age groups: 15–19-year-old (n = 5,558), 35–44-year-old (n = 6,051), and older people of 65 years or more (n = 5,951) participated in the survey. The selection was made by probabilistic sample by conglomerates in two stages. The endpoint variable was the impact of oral health on daily activities, evaluated by the Oral Impacts on Daily Performances questionnaire, containing questions about eating, talking, oral hygiene, relaxation, sports practice, smile, study or work, social contact, and sleep. Oral Impacts on Daily Performances was dichotomized with and without impact. The independent variables were sociodemographic, clinical and access variables, divided into three blocks. A hierarchical multiple logistic regression analysis was performed considering the complex sampling plan of clusters. Each observation received a specific weight, depending on the location that resulted in weighted frequencies and adjusted for the design effect. RESULTS: The presence of oral health impact was observed in 27.9% of the individuals. In block 1, female gender and black/brown ethnic group had a greater chance of impact of oral health on quality of life, as well as the adults and the older adults in relation to adolescents. In block 2, family income up to R$1,500 was associated with the presence of impact. In block 3, individuals who reported toothache, used the public service and sought dental treatment had a greater chance of impact. CONCLUSIONS: Sociodemographic, clinical and access to health services variables influence the impact of oral health on the daily activities of adolescents, adults and older adults. PMID:29668813

Abdominal massage for neurogenic bowel dysfunction in people with multiple sclerosis (AMBER - Abdominal Massage for Bowel Dysfunction Effectiveness Research): study protocol for a randomised controlled trial.

PubMed

McClurg, Doreen; Goodman, Kirsteen; Hagen, Suzanne; Harris, Fional; Treweek, Sean; Emmanuel, Anton; Norton, Christine; Coggrave, Maureen; Doran, Selina; Norrie, John; Donnan, Peter; Mason, Helen; Manoukian, Sarkis

2017-03-29

Multiple sclerosis (MS) is a life-long condition primarily affecting younger adults. Neurogenic bowel dysfunction (NBD) occurs in 50-80% of these patients and is the term used to describe constipation and faecal incontinence, which often co-exist. Data from a pilot study suggested feasibility of using abdominal massage for the relief of constipation, but the effectiveness remains uncertain. This is a multi-centred patient randomised superiority trial comparing an experimental strategy of once daily abdominal massage for 6 weeks against a control strategy of no massage in people with MS who have stated that their constipation is bothersome. The primary outcome is the Neurogenic Bowel Dysfunction Score at 24 weeks. Both groups will receive optimised advice plus the MS Society booklet on bowel management in MS, and will continue to receive usual care. Participants and their clinicians will not be blinded to the allocated intervention. Outcome measures are primarily self-reported and submitted anonymously. Central trial staff who will manage and analyse the trial data will be unaware of participant allocations. Analysis will follow intention-to-treat principles. This pragmatic randomised controlled trial will demonstrate if abdominal massage is an effective, cost-effective and viable addition to the treatment of NBD in people with MS. ClinicalTrials.gov, ISRCTN85007023 . Registered on 10 June 2014.

Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study.

PubMed

Kappos, Ludwig; Bar-Or, Amit; Cree, Bruce A C; Fox, Robert J; Giovannoni, Gavin; Gold, Ralf; Vermersch, Patrick; Arnold, Douglas L; Arnould, Sophie; Scherz, Tatiana; Wolf, Christian; Wallström, Erik; Dahlke, Frank

2018-03-31

No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18-60 years) with SPMS and an Expanded Disability Status Scale score of 3·0-6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65-0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Novartis Pharma AG. Copyright © 2018 Elsevier Ltd. All rights reserved.

Daily vs every other day administration of G-CSF following autologous peripheral stem cell transplantation: a prospective randomized study.

PubMed

Ozkan, Hasan Atilla; Ozer, Ufuk Guney; Bal, Cengiz; Gulbas, Zafer

2013-10-01

The purpose of the study was to evaluate whether every other day administration of G-CSF was as safe and efficient as daily administration of G-CSF on neutrophil engraftment following autologous peripheral stem cell transplantation (APSCT). Duration of G-CSF administration, incidence of blood stream infections, duration of febrile neutropenia, duration of non-prophylactic antibiotic therapy, transfusion requirements, duration of hospitalization and G-CSF costs were also studied. Forty-seven patients with diagnosis of lymphoma and multiple myeloma undergoing APSCT were randomized to receive post-transplant daily or every other day G-CSF therapy both beginning on day +1. Both groups were comparable with regard to patient characteristics. There was no significant difference in time to neutrophil engraftment (p=0.31). The duration of G-CSF administration was significantly less in the every other day group (p<0.001). There were no detectable differences seen in the number of febrile days, duration of non-prophylactic antibiotics, the incidence of blood stream infections, transfusion requirements and the duration of hospitalization. There was a trend towards a faster platelet recovery in the every other day group, although the difference was not statistically significant (p=0.059). The number of doses of G-CSF used per transplant is significantly reduced, resulting in a significant reduction in drug costs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Beneficial effects of curcumin nano-emulsion on spermatogenesis and reproductive performance in male rats under protein deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content.

PubMed

Ahmed-Farid, Omar A H; Nasr, Maha; Ahmed, Rania F; Bakeer, Rofanda M

2017-09-02

Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats. Juvenile rats were fed the protein deficient diet (PDD) for 75 days. Starting from day 60 the rats were divided into 4 groups and given the corresponding treatments for the last 15 days orally and daily as follows: 1st group; curcumin group (C) received 50 mg/kg curcumin p.o. 2 nd group; curcumin nano-form low dose group (NCL) received 2.5 mg/kg nano-curcumin. 3rd group; curcumin nano-form high dose group (NCH) received 5 mg/kg nano-curcumin. 4th group served as malnutrition group (PDD group) receiving the protein deficient diet daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. A normal control group was kept under the same conditions for the whole experiment and received normal diet according to nutrition requirement center daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. PDD induced significant (P < 0.05) reduction in serum testosterone level, sperm motility, testicular GSH, CAT, SOD, testicular cell energy (ATP, ADP and AMP), essential and non-essential amino acids in seminal plasma, an increase in testicular MDA, NOx, GSSG and 8-OHDG. Data was confirmed by histological examination and revealed pathological alteration in the PDD group. Ingestion of curcumin (50 mg/kg) and curcumin nano-emulsion (2.5 and 5 mg/kg) showed significant (P< 0.05) amelioration effects against PDD-induced disrupted reproductive performance as well as biochemical and pathological alterations and the overall results of the nano-emulsion (5 mg/kg) were comparable to curcumin (50 mg/kg). The present study suggests that administration of curcumin nano-emulsion as a daily supplement would be beneficial in malnutrition- induced troubled male reproductive performance and spermatogenesis cases.

Conversion from thrice- to twice-daily pregabalin dosing for pain: Economic and clinical outcomes in a veteran population.

PubMed

Okolo, Chike; Malmstrom, Robert; Duncan, Karsten; Lopez, Julio

2015-09-01

Results of a study analyzing economic and clinical outcomes one year after conversion from thrice- to twice-daily pregabalin dosing for pain are presented. A retrospective chart review was conducted at two Veterans Affairs facilities. The analyzed population included all patients receiving pregabalin for pain whose dosing was converted from thrice- to twice-daily pregabalin dosing during a one-year period. The primary endpoint was the economic impact of the conversion. Secondary endpoints included reversion to thrice-daily pregabalin dosing, pregabalin discontinuation, addition of medications for pain, and unscheduled neuropathy-related visits. Among the 57 patients included in the data analysis, 41 continued to take pregabalin twice daily, 10 had pregabalin discontinued, and 6 had dosing reverted to thrice daily. The mean age of patients and the distribution of add-on pain medications did not differ significantly between patients whose pregabalin dosing frequency remained at twice daily and patients whose frequency reverted to thrice daily. The costs associated with pregabalin therapy differed significantly between the preconversion and postconversion periods. A savings of $115,867 was realized from this conversion for both facilities combined over the course of one year. In patients receiving pregabalin for pain, conversion from thrice- to twice-daily pregabalin dosing-while maintaining the same daily dose-resulted in substantial cost savings while having little effect on clinical outcomes. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Socioeconomic, Family, and Pediatric Practice Factors Affecting the Level of Asthma Control

PubMed Central

Bloomberg, Gordon R; Banister, Christina; Sterkel, Randall; Epstein, Jay; Bruns, Julie; Swerczek, Lisa; Wells, Suzanne; Yan, Yan; Garbutt, Jane M

2008-01-01

Background Multiple issues bear on effective control of childhood asthma. Objective To identify factors related to the level of asthma control in children receiving asthma care from community pediatricians. Patients and Methods Data for 362 children participating in an intervention study to reduce asthma morbidity were collected by telephone administered questionnaire. Level of asthma control (“well controlled,” partially controlled,” or “poorly controlled”) was derived from measures of recent impairment (symptoms, activity limitations, albuterol use) and the number of exacerbations in a 12 month period. Data also included demographic characteristics, asthma-related quality of life, pediatric management practices, and medication usage. Univariable and multivariable analyses were used to identify factors associated with poor asthma control and to explore the relationship between control and use of daily controller medications. Results Asthma was “well controlled” for 24% of children, “partially controlled” for 20%, and “poorly controlled” for 56%. Medicaid insurance (p=0.016), the presence of another family member with asthma (p=0.0168), and outside the home maternal employment, (p=0.025), were significant univariable factors associated with poor asthma control. Medicaid insurance had an independent association with poor control (OR 0.49, 95% CI 0.28-0.9). Seventy-six percent of children were reported by parents as receiving a daily controller medication. Comparison of guidelines recommended controller medication with level of control indicated that a higher step level of medication would have been appropriate for 74% of these children. Significantly lower overall quality of life scores were observed in both parents and children with poor control. (ANOVA, p<0.05) Conclusion Despite substantial use of daily controller medication, children with asthma continue to experience poorly controlled asthma and reduced quality of life. While Medicaid insurance and aspects of family structure are significant factors associated with poorly controlled asthma, attention to medication use and quality of life indicators may further reduce morbidity. PMID:19255010

Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial.

PubMed

Radmanesh, Mohammad; Rafiei, Behnam; Moosavi, Zahra-Beigum; Sina, Niloofar

2011-10-01

Methotrexate (MTX) treatment for psoriasis is most often administered weekly, because the drug has been considered more hepatotoxic when taken daily. However, some patients may tolerate smaller, more frequent doses better. To study the efficacy and toxicity of daily vs. weekly MTX. In a randomized controlled trial, 101 patients with generalized plaque psoriasis received oral MTX 2.5 mg daily for weeks, 4 weeks and monthly for a total of 4 months. Changes in PASI scores were classified into three categories: >75% improvement was considered significant; 25-75% moderate; and <25% poor. Sixty Group 1 patients and 81 Group 2 patients showed a significant response (P-value 0.001); 19 patients in Group 1 and 14 in Group 2 responded moderately; 22 patients in Group 1 and six patients from Group 2 responded poorly. Forty-five patients in Group 1 and 33 in Group 2 developed transient increases in liver enzymes (P-value 0.11). Nausea, headache, fatigue, and gastrointestinal upset were noted in four Group 1 patients and 30 Group 2 patients (P-value 0.0001). Nausea, vomiting, headache, and fatigue were significantly less common side effects in our patients who received MTX daily, but liver enzyme abnormalities were less common, and clinical efficacy was greater in the patients who received MTX weekly. © 2011 The International Society of Dermatology.

Church-Based Social Support Among Caribbean Blacks in the United States

PubMed Central

Nguyen, Ann W.; Taylor, Robert Joseph; Chatters, Linda M.

2016-01-01

An emerging body of research notes the importance of church-based social support networks in the daily lives of Americans. However, few studies examine church-based support, and especially among ethnic subgroups within the U.S. Black population, such as Caribbean Blacks. This study uses data from the National Survey of American Life (NSAL) to examine demographic and religious participation (e.g., attendance, interaction) correlates of church-based social support (e.g., receipt of emotional support, receipt of general support, provision of support to others, and negative interaction) among Caribbean Blacks residing in the U.S. Multiple regression analyses indicated that religious participation was associated with all four dependent variables. Church attendance was positively associated with receiving emotional support, general social support, and providing support to others, but was not associated with negative interaction. Frequency of interaction with fellow congregants was positively associated with receiving emotional support, receiving general support, providing support to others and negative interaction. Demographic findings indicated that women provided more support to church members and experienced more negative interactions with members than did men. Education was positively associated with frequency of support; household income was negatively associated with receiving emotional support and providing social support to others. Findings are discussed in relation to the role of church-based support networks in the lives of Caribbean Black immigrants and communities. PMID:27942078

Effects of combined fine motor skill and cognitive therapy to cognition, degree of dementia, depression, and activities of daily living in the elderly with Alzheimer's disease.

PubMed

Lee, Jin; Lee, ByoungHee; Park, YuHyung; Kim, Yumi

2015-10-01

[Purpose] This study evaluated the effects of combined fine motor skill and cognitive therapies on cognition, depression, and activities of daily living in elderly patients with Alzheimer's disease (AD). [Subjects and Methods] Twenty-six participants comprised 2 groups. The experimental group (n=13) received combined fine motor skill and cognitive therapy, and the control group (n=13) received only general medical care. [Results] The experimental group showed improvements in cognition, degree of dementia, depression, and activities of daily living compared to the control group. However, there were no significant differences between the two groups. [Conclusion] These results suggest that combined fine motor skill and cognitive therapy improves cognition, degree of dementia, depression, and daily living in elderly patients with AD. These therapies would therefore be effective as general medical care strategies.

Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding.

PubMed

Pannucci, Christopher J; Fleming, Kory I; Momeni, Arash; Prazak, Ann Marie; Agarwal, Jayant; Rockwell, W Bradford

2018-06-01

Low anti-factor Xa level, indicative of inadequate enoxaparin dosing, has a significant association with 90-day venous thromboembolism events. The authors examined the pharmacodynamics of enoxaparin 40 mg twice daily and its correlation with anti-factor Xa level, postoperative venous thromboembolism, and bleeding. Adult patients were admitted after plastic and reconstructive surgery and received enoxaparin 40 mg twice daily. Peak anti-factor Xa levels, which quantify enoxaparin's antithrombotic effect, were drawn, with a goal level of 0.2 to 0.4 IU/ml. Ninety-day symptomatic venous thromboembolism and clinically relevant bleeding were identified. The authors enrolled 118 patients who received enoxaparin 40 mg twice daily. Of these patients, 9.6 percent had low peak anti-factor Xa levels (<0.2 IU/ml), 62.6 percent had in-range peak anti-factor Xa levels (0.2 to 0.4 IU/ml), and 27.8 percent had high anti-factor Xa levels (>0.4 IU/ml). With enoxaparin 40 mg twice daily, 90.4 percent of patients received at least adequate prophylaxis. Patient weight predicted the rapidity of enoxaparin metabolism. Zero acute 90-day venous thromboembolism occurred. Eight patients (6.8 percent) had clinically relevant 90-day bleeding: clinical consequences ranged from cessation of enoxaparin prophylaxis to transfusion to operative hematoma evacuation. When enoxaparin 40 mg twice daily is provided, 90 percent of patients receive at least adequate venous thromboembolism prophylaxis (anti-factor Xa level >0.2 IU/ml). However, 27 percent of the overall population is overtreated (anti-factor Xa level >0.4 IU/ml). These pharmacodynamics data likely explain the low rate of 90-day acute venous thromboembolism (0 percent) and the high rate of clinically relevant bleeding (6.8 percent) observed. Future studies are needed to better optimize the risks and benefits of enoxaparin prophylaxis in plastic and reconstructive surgery patients. Therapeutic, IV.

Foals raised on pasture with or without daily pyrantel tartrate feed additive: comparison of parasite burdens and host responses following experimental challenge with large and small strongyle larvae.

PubMed

Monahan, C M; Chapman, M R; Taylor, H W; French, D D; Klei, T R

1997-12-31

Three groups of foals were raised under different management programs in this study: Group 1 (n = 6) and Group 2 (n = 6) were raised with their dams on pasture; Group 3 foals (n = 5) were raised under parasite-free conditions. Mares and foals of Group 1 received daily pyrantel tartrate (PT) treatment with their pelleted feed ration, whereas mares and foals of Groups 2 and 3 received only the pelleted ration. Pasture-reared foals were weaned and moved to a heavily contaminated pasture for 5 weeks. Group 1 foals continued to receive daily PT treatment whereas Group 2 foals received only the pelleted feed ration. Following this period, all foals were moved into box stalls. Half of each group was challenged with 10(3) Strongylus vulgaris infective third-stage larvae (L3), 5 x 10(3) Strongylus edentatus L3 and 10(5) mixed cyathostome L3; the remaining half served as unchallenged controls. Necropsy examinations were performed 6-week post-challenge for evaluation of parasite burdens and lesions. Daily PT treatment of Group 1 reduced the patent cyathostome infections of both mares and foals and was effective in reducing pasture burdens of infective larvae. Daily treatment of Group 1 foals during weaning continued to suppress EPG levels; however, it did not prevent large strongyle infections during the weaning period. Group 1 foals were more sensitive to challenge than Group 2 foals, which did not exhibit any post-challenge disturbances. Group 1 foals were equally susceptible to challenge as parasite-free foals.

Acetylsalicylic Acid Daily vs Acetylsalicylic Acid Every 3 Days in Healthy Volunteers: Effect on Platelet Aggregation, Gastric Mucosa, and Prostaglandin E2 Synthesis.

PubMed

Ferreira, Plinio Minghin Freitas; Gagliano-Jucá, Thiago; Zaminelli, Tiago; Sampaio, Marinalva Ferreira; Blackler, Rory Willian; Trevisan, Miriam da Silva; Novaes Magalhães, Antônio Frederico; De Nucci, Gilberto

2016-07-01

Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81 mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan and acetylsalicylic acid every day and the other receiving losartan every day and acetylsalicylic acid every 3 days. Twenty-eight healthy volunteers from both sexes received either 50 mg losartan and acetylsalicylic acid 81 mg daily or 50 mg losartan and acetylsalicylic acid 81 every 3 days with placebo on the other days. Therapy was delivered for 30 days for both groups. Gastric endoscopy was performed before and after treatment period. Biopsies were collected for PGE2 quantification. Platelet function tests were carried out before and during treatment and TXB2 release on platelet rich plasma was measured. The every 3 day low-dose acetylsalicylic acid regimen produced complete inhibition of platelet aggregation compared to the daily treatment. Thromboxane B2 release was substantially abolished for both groups during treatment. There was no significant difference on the endoscopic score of both treatment groups after the 30-day treatment (P = .215). There was over 50% suppression of antrum PGE2 content on volunteers receiving acetylsalicylic acid daily (P = .0016), while for the every 3 day dose regimen there was no significant difference between pre and post-treatment antrum PGE2 dosages (P = .4193). Since PGE2 is involved in gastric healing, we understand that this new approach could be safer and as efficient as the standard daily therapy on a long-term basis. © 2015, The American College of Clinical Pharmacology.

Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12-month data from the OpT2mise randomized trial.

PubMed

Aronson, R; Reznik, Y; Conget, I; Castañeda, J A; Runzis, S; Lee, S W; Cohen, O

2016-05-01

To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. After a 2-month dose-optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6-month continuation phase (CP). The primary endpoint was the between-group difference in change in mean HbA1c from baseline to the end of the RP. The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (-1.1 ± 1.2% vs -0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI-pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12‐month data from the OpT2mise randomized trial

PubMed Central

Reznik, Y.; Conget, I.; Castañeda, J. A.; Runzis, S.; Lee, S. W.; Cohen, O.

2016-01-01

Aims To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. Methods After a 2‐month dose‐optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6‐month continuation phase (CP). The primary endpoint was the between‐group difference in change in mean HbA1c from baseline to the end of the RP. Results The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (−1.1 ± 1.2% vs −0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI–pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. Conclusions Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes. PMID:26854123

Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study.

PubMed

van der Heijde, Désirée; Tanaka, Yoshiya; Fleischmann, Roy; Keystone, Edward; Kremer, Joel; Zerbini, Cristiano; Cardiel, Mario H; Cohen, Stanley; Nash, Peter; Song, Yeong-Wook; Tegzová, Dana; Wyman, Bradley T; Gruben, David; Benda, Birgitta; Wallenstein, Gene; Krishnaswami, Sriram; Zwillich, Samuel H; Bradley, John D; Connell, Carol A

2013-03-01

The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12-month interim analysis are reported. In this double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo-treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step-down procedure. At month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo (P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were -0.40 (significance not declared due to step-down procedure) and -0.54 (P < 0.0001), respectively, versus -0.15 for placebo. At month 6, rates of remission (defined as a value <2.6 for the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate) for tofacitinib at 5 mg and 10 mg twice daily were 7.2% (significance not declared due to step-down procedure) and 16.0% (P < 0.0001), respectively, versus 1.6% for placebo. The safety profile was consistent with findings in previous studies. Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX. Copyright © 2013 by the American College of Rheumatology.

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

PubMed Central

Suvannasankha, Attaya; Fay, Joseph W.; Arnulf, Bertrand; Kaufman, Jonathan L.; Ifthikharuddin, Jainulabdeen J.; Weiss, Brendan M.; Krishnan, Amrita; Lentzsch, Suzanne; Comenzo, Raymond; Wang, Jianping; Nottage, Kerri; Chiu, Christopher; Khokhar, Nushmia Z.; Ahmadi, Tahamtan; Lonial, Sagar

2017-01-01

Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points. Patients (N = 103) received a median (range) of 4 (1-13) prior therapies; 76% received ≥3 prior therapies. The safety profile of daratumumab plus pom-dex was similar to that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) and a higher incidence of neutropenia, although without an increase in infection rate. Common grade ≥3 adverse events were neutropenia (78%), anemia (28%), and leukopenia (24%). ORR was 60% and was generally consistent across subgroups (58% in double-refractory patients). Among patients with a complete response or better, 29% were MRD negative at a threshold of 10−5. Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months and median overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival rate was 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials.gov as #NCT01998971. PMID:28637662

Parsimonious model for blood glucose level monitoring in type 2 diabetes patients.

PubMed

Zhao, Fang; Ma, Yan Fen; Wen, Jing Xiao; DU, Yan Fang; Li, Chun Lin; Li, Guang Wei

2014-07-01

To establish the parsimonious model for blood glucose monitoring in patients with type 2 diabetes receiving oral hypoglycemic agent treatment. One hundred and fifty-nine adult Chinese type 2 diabetes patients were randomized to receive rapid-acting or sustained-release gliclazide therapy for 12 weeks. Their blood glucose levels were measured at 10 time points in a 24 h period before and after treatment, and the 24 h mean blood glucose levels were measured. Contribution of blood glucose levels to the mean blood glucose level and HbA1c was assessed by multiple regression analysis. The correlation coefficients of blood glucose level measured at 10 time points to the daily MBG were 0.58-0.74 and 0.59-0.79, respectively, before and after treatment (P<0.0001). The multiple stepwise regression analysis showed that the blood glucose levels measured at 6 of the 10 time points could explain 95% and 97% of the changes in MBG before and after treatment. The three blood glucose levels, which were measured at fasting, 2 h after breakfast and before dinner, of the 10 time points could explain 84% and 86% of the changes in MBG before and after treatment, but could only explain 36% and 26% of the changes in HbA1c before and after treatment, and they had a poorer correlation with the HbA1c than with the 24 h MBG. The blood glucose levels measured at fasting, 2 h after breakfast and before dinner truly reflected the change 24 h blood glucose level, suggesting that they are appropriate for the self-monitoring of blood glucose levels in diabetes patients receiving oral anti-diabetes therapy. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Falls prevention and balance rehabilitation in multiple sclerosis: a bi-centre randomised controlled trial.

PubMed

Cattaneo, Davide; Rasova, Kamila; Gervasoni, Elisa; Dobrovodská, Gabriela; Montesano, Angelo; Jonsdottir, Johanna

2018-03-01

People with Multiple Sclerosis (PwMS) have a high incidence of accidental falls that have a potentially detrimental effect on their daily life participation. The effect of balance specific rehabilitation on clinical balance measures and frequency of falls in PwMS was studied. A bi-centre randomised rater-blinded controlled trial. Participants in both groups received 20 treatment sessions. Participants in the intervention group received treatment aimed at improving balance and mobility. Participants in the control group received treatments to reduce limitations at activity and body function level. Primary measures were frequency of fallers (>1 fall in two months) and responders (>3 points improvement) at the Berg Balance Scale (BBS). Data was analysed according to an intention to treat approach. One hundred and nineteen participants were randomised. Following treatment frequency of fallers was 22% in the intervention group and 23% in the control group, odds ratio (OR) and (confidence limits): 1.05 (0.41 to 2.77). Responders on the BBS were 28% in the intervention group and 33% in the control group, OR = 0.75 (0.30 to 1.91). At follow up ORs for fallers and responders at BBS were 0.98 (0.48 to 2.01) and 0.79 (0.26 to 2.42), respectively. Twenty sessions 2-3 times/week of balance specific rehabilitation did not reduce fall frequency nor improve balance suggesting the need for more frequent and challenging interventions. Implications for Rehabilitation Programs for balance rehabilitation can improve balance but their effects in fall prevention are unclear. Twenty treatments sessions 2/3 times per week did not reduced frequency of falls in MS. The comparison with similar studies suggests that higher intensity of practice of highly challenging balance activities appears to be critical to maximizing effectiveness.

Dual Tobacco User Subtypes in the U.S. Air Force: Dependence, Attitudes, and Other Correlates of Use

PubMed Central

Kram, Yoseph; Klesges, Robert C.; Talcott, Wayne; Neilands, Torsten B.; Ling, Pamela M.

2014-01-01

Introduction: To describe the characteristics associated with patterns of daily and dual tobacco use among U.S. Air Force (USAF) personnel transitioning from basic military training to technical training. Methods: Cross-sectional survey of USAF personnel in Technical Training School at Lackland Air Force Base (N = 8,956, response rate: 73%). Logistic regression analyzed the association of predictor variables between daily smokers, daily smokeless tobacco (ST) users, daily smokers who used ST nondaily, daily ST users who smoked cigarettes nondaily, and daily users of both cigarettes and ST. Results: Compared to daily smokers, participants who were daily smokers/nondaily ST users were more likely to be male, would use ST and multiple forms of tobacco in the future, reported more friends using ST and cigarettes, and were more susceptible to tobacco advertising. Compared to daily ST users, daily ST users/nondaily cigarette users were more likely to live in the Midwest, would use multiple forms of tobacco in the future, reported more friends smoked cigarettes and used ST, and were more likely to try a product that claimed to be safer than cigarettes. Daily users of both cigarettes and ST were significantly more likely to be nicotine dependent than daily smokers/nondaily ST users and daily ST users/nondaily smokers. Conclusions: Dual users are heterogeneous groups of tobacco users who are at high risk for continued tobacco use. Daily users of both cigarettes and ST have higher levels of nicotine dependence, even when compared to other dual users. Specific interventions targeted at dual users are needed in this increasingly prevalent and high-risk population. PMID:24721813

Dual tobacco user subtypes in the U.S. Air Force: dependence, attitudes, and other correlates of use.

PubMed

Kram, Yoseph; Klesges, Robert C; Ebbert, Jon O; Talcott, Wayne; Neilands, Torsten B; Ling, Pamela M

2014-09-01

To describe the characteristics associated with patterns of daily and dual tobacco use among U.S. Air Force (USAF) personnel transitioning from basic military training to technical training. Cross-sectional survey of USAF personnel in Technical Training School at Lackland Air Force Base (N = 8,956, response rate: 73%). Logistic regression analyzed the association of predictor variables between daily smokers, daily smokeless tobacco (ST) users, daily smokers who used ST nondaily, daily ST users who smoked cigarettes nondaily, and daily users of both cigarettes and ST. Compared to daily smokers, participants who were daily smokers/nondaily ST users were more likely to be male, would use ST and multiple forms of tobacco in the future, reported more friends using ST and cigarettes, and were more susceptible to tobacco advertising. Compared to daily ST users, daily ST users/nondaily cigarette users were more likely to live in the Midwest, would use multiple forms of tobacco in the future, reported more friends smoked cigarettes and used ST, and were more likely to try a product that claimed to be safer than cigarettes. Daily users of both cigarettes and ST were significantly more likely to be nicotine dependent than daily smokers/nondaily ST users and daily ST users/nondaily smokers. Dual users are heterogeneous groups of tobacco users who are at high risk for continued tobacco use. Daily users of both cigarettes and ST have higher levels of nicotine dependence, even when compared to other dual users. Specific interventions targeted at dual users are needed in this increasingly prevalent and high-risk population. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PubMed

Bobholz, Julie A; Rao, Stephen M

2003-06-01

Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial.

PubMed

Lalezari, Jacob P; Latiff, Gulam H; Brinson, Cynthia; Echevarría, Juan; Treviño-Pérez, Sandra; Bogner, Johannes R; Thompson, Melanie; Fourie, Jan; Sussmann Pena, Otto A; Mendo Urbina, Fernando C; Martins, Marcelo; Diaconescu, Iulian G; Stock, David A; Joshi, Samit R; Hanna, George J; Lataillade, Max

2015-10-01

BMS-663068 is an oral prodrug of BMS-626529, an attachment inhibitor that binds to HIV-1 gp120, blocking viral attachment to host CD4 cells. AI438011 is an ongoing trial investigating the efficacy, safety, and dose-response of BMS-663068 in treatment-experienced, HIV-1-infected patients. Herein we present the results of the primary analysis. AI438011 is a phase 2b, randomised, active-controlled trial, at 53 hospitals and outpatient clinics across ten countries in North and South America, Europe, and Africa. Individuals with an HIV-1 RNA viral load of at least 1000 copies per mL and a BMS-626529 half-maximum inhibitory concentration lower than 100 nmol/L were randomly assigned (1:1:1:1:1) to receive either BMS-663068 at 400 mg twice daily, 800 mg twice daily, 600 mg once daily, or 1200 mg once daily or ritonavir-boosted atazanavir (300 mg of atazanavir and 100 mg of ritonavir once daily), each with 400 mg of raltegravir twice daily and 300 mg of tenofovir disoproxil fumarate once daily as a backbone. The sponsor, participants, and investigators were masked for BMS-663068 dose but not for allocation. Primary endpoints were the proportion of patients with an HIV-1 RNA viral load less than 50 copies per mL (response rate) at week 24 and the frequency of serious adverse events and adverse events leading to discontinuation, up to the week 24 analysis. The primary analyses included all patients who received at least one dose of study drug (modified intention-to-treat population). This study is registered at ClinicalTrials.gov, NCT01384734. Between July 26, 2011, and July 16, 2012, 581 participants were assessed for eligibility. Of these, 254 patients were randomly assigned to receive either BMS-663068 (n=52 for the 400 mg twice daily group, n=50 for the 800 mg twice daily group, n=51 for the 600 mg once daily group, and n=50 for the 1200 mg once daily group) or ritonavir-boosted atazanavir (n=51). 200 patients received at least one dose of BMS-663068, and 51 patients received at least one dose of ritonavir-boosted atazanavir. At week 24, 40 (80%) of 50 patients in the BMS-663068 400 mg twice daily group, 34 (69%) of 49 patients in the 800 mg twice daily group, 39 (76%) of 51 patients in the 600 mg once daily group, and 36 (72%) of 50 patients in the 1200 mg once daily group had an HIV-1 RNA viral load less than 50 copies per mL, compared with 38 (75%) of 51 patients in the ritonavir-boosted atazanavir group. Serious adverse events were noted in 13 (7%) of 200 patients in the BMS-663068 groups and five (10%) of the 51 patients in the ritonavir-boosted atazanavir group. Four (2%) of the 200 patients in the BMS-663068 groups and two (4%) of the 51 patients in the ritonavir-boosted atazanavir group discontinued because of adverse events. No serious adverse events or adverse events leading to discontinuation were BMS-663068-related. Grade 2-4 adverse events related to study drug(s) occurred in 17 (9%) of 200 patients across the BMS-663068 groups and 14 (27%) of 51 patients in the ritonavir-boosted atazanavir group. For the BMS-663068 groups these events were mostly single instances with no dose relation and for the ritonavir-boosted atazanavir group these were mostly gastrointestinal or hepatobiliary disorders associated with hyperbilirubinaemia. In a comparison with ritonavir-boosted atazanavir, efficacy and safety of BMS-663068 up to the week 24 analysis support continued development of BMS-663068, which is being assessed in a phase 3 trial in heavily treatment-experienced individuals. Bristol-Myers Squibb. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hypofibrinogenemia induced by tigecycline: a potentially life-threatening coagulation disorder.

PubMed

Sabanis, Nikolaos; Paschou, Eleni; Gavriilaki, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2015-01-01

A 74-year-old female patient with end-stage renal disease, undergoing periodic hemodialysis, was hospitalized due to infection by multidrug-resistant Acinetobacter baumannii after hip replacement surgery. She was treated with tigecycline, a glycylcycline agent. Subsequently she developed coagulation disorders as substantiated by increased international normalized ratio (INR), prolonged partial thromboplastin time (aPTT), and severe hypofibrinogenemia, followed by transaminasemia, cholestasis, and anemia. Ultrasonography and computed tomography revealed no underlying pathological entities. Tigecycline was discontinued and the patient underwent daily hemodialysis and received multiple fresh frozen plasma transfusions. Additionally, she was treated with colistin. Her clinical and laboratory status improved. We suggest that patients treated with tigecycline should be monitored for changes in INR, aPTT, and fibrinogen levels to avoid severe, life-threatening coagulation disturbances.

Sacubitril/Valsartan in Clinical Practice: A Report of 2 Cases.

PubMed

Cosentino, Eugenio

Following the results of the PARADIGM-HF trial, the European Society of Cardiology (ESC) guidelines recommend sacubitril/valsartan to replace ACE inhibitors in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy and who fit trial criteria. However, the optimal use of sacubitril/valsartan in clinical practice needs further investigation. We report here the cases of 2 patients with HFrEH successfully treated with sacubitril/valsartan in our daily practice. Both subjects presented multiple comorbidities and received an implantable cardioverter defibrillator in primary prevention. In both patients, therapy with sacubitril/valsartan led to prompt (30 days) amelioration of heart function, with a corresponding decrease in NHYA class and without any relevant safety issue. © 2017 S. Karger AG, Basel.

Pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans.

PubMed

Court, Michael H; Robbins, Alison H; Whitford, Anne M; Beck, Erika V; Tseng, Flo S; Reeder, DeeAnn M

2017-01-01

OBJECTIVE To determine the pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans. ANIMALS 123 bats from a P destructans-infected hibernation site in Virginia. PROCEDURES 3 bats were euthanized and necropsied to confirm the presence of P destructans within the population. The remaining 120 bats were systematically assigned to 6 groups (20 bats/group). Bats in each of 3 groups received 6, 20, or 60 mg of terbinafine/kg, SC, once daily for 10 days. Bats in another group received 200 mg of terbinafine/kg, SC, once daily for 5 days. Bats in 1 group received the terbinafine vehicle solution (0.1 mL/kg, SC, once daily for 10 days). Bats in the remaining group did not receive any treatment. Following the treatment period (days 1 through 10), bats were housed in a hibernation chamber and monitored daily until euthanasia on day 42, 75, or 109. Tissue specimens were collected from all bats as soon as possible after death or euthanasia to determine terbinafine concentration. Within each group and tissue type, terbinafine concentration data were pooled, and pharmacokinetic parameters were calculated by noncompartmental methods. RESULTS Adverse neurologic effects and a high mortality rate before day 10 were observed in bats that received the highest terbinafine dose (200 mg/kg) but not those that received lower doses. Presumed therapeutic terbinafine concentrations (≥ 2 μg/g) were maintained in skin and wing for at least 30 and 6 days in bats that received the 60 and 20 mg/kg doses, respectively, but were not achieved in most bats that received the 6 mg/kg dose. Tissue terminal half-life ranged from 14 to 22 days. Terbinafine concentration in hair was positively correlated with that in skin and wing. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated terbinafine doses > 6 but < 200 mg/kg should be further evaluated for the treatment of P destructans-infected bats. Collection of serial hair specimens may represent a noninvasive method for monitoring terbinafine concentration in treated bats.

Using porches to decrease feces painting in rhesus macaques (Macaca mulatta).

PubMed

Gottlieb, Daniel H; O'Connor, Jillann Rawlins; Coleman, Kristine

2014-11-01

The goal of this project was to evaluate the efficacy of a porch in decreasing feces painting in captive rhesus macaques. The porch is a small extension that is hung on the outside of a monkey's primary home cage. Porches provide many potential benefits to indoor-housed macaques, including opportunities to perch above the ground, additional space, and increased field of view. Rates of feces painting, an abnormal behavior in which the animal smears or rubs feces on a surface, were compared in 3 situations: with porch enrichment, with 'smear board' enrichment (a foraging device commonly used to decrease feces painting), and without either enrichment item. Feces painting was evaluated daily by using a 5-point scale that ranged from 0, no feces present, to 4, multiple large areas of feces. We found that subjects received significantly lower feces painting scores when given porch enrichment or smear board enrichment compared with baseline. Furthermore, subjects received significantly lower feces painting scores with porch enrichment than smear board enrichment. These results demonstrate that the porch is an effective tool to decrease feces painting in captive macaques.

Using Porches to Decrease Feces Painting in Rhesus Macaques (Macaca mulatta)

PubMed Central

Gottlieb, Daniel H; O'Connor, Jillann Rawlins; Coleman, Kristine

2014-01-01

The goal of this project was to evaluate the efficacy of a porch in decreasing feces painting in captive rhesus macaques. The porch is a small extension that is hung on the outside of a monkey's primary home cage. Porches provide many potential benefits to indoor-housed macaques, including opportunities to perch above the ground, additional space, and increased field of view. Rates of feces painting, an abnormal behavior in which the animal smears or rubs feces on a surface, were compared in 3 situations: with porch enrichment, with ‘smear board’ enrichment (a foraging device commonly used to decrease feces painting), and without either enrichment item. Feces painting was evaluated daily by using a 5-point scale that ranged from 0, no feces present, to 4, multiple large areas of feces. We found that subjects received significantly lower feces painting scores when given porch enrichment or smear board enrichment compared with baseline. Furthermore, subjects received significantly lower feces painting scores with porch enrichment than smear board enrichment. These results demonstrate that the porch is an effective tool to decrease feces painting in captive macaques. PMID:25650971

Significant partial response of metastatic intra-abdominal and pelvic round cell liposarcoma to a small-molecule VEGFR-2 tyrosine kinase inhibitor apatinib

PubMed Central

Dong, Min; Bi, Jingwang; Liu, Xiaohong; Wang, Baocheng; Wang, Jun

2016-01-01

Abstract Introduction: Myxoid/round cell liposarcoma is the second most common subtype of liposarcoma. Chemotherapy and radiotherapy have a limited efficacy for treating advanced myxoid/round cell liposarcoma, with relatively serious side effects. Case presentation: We herein present a 68-year-old Chinese woman initially diagnosed with advanced multiple intra-abdominal and pelvic round cell liposarcoma. She refused to receive cytotoxic chemotherapy and received apatinib as the first-line therapy, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 that has been used in the treatment of patients with metastatic gastric cancer who progressed with 2 or more chemotherapy regimens. This patient was partially responsive to apatinib with a dose of 500 mg daily. No serious drug-related side effects were observed. Conclusion: Our findings indicate that some cases of liposarcoma may be responsive to antiangiogenic agent apatinib. Randomized clinical studies are needed to further confirm the efficacy and safety of apatinib in the clinical treatment of liposarcoma. PMID:27495042

The use of colonic irrigation to control fecal incontinence in dogs with colostomies.

PubMed

Williams, F A; Bright, R M; Daniel, G B; Hahn, K A; Patton, S A

1999-01-01

To determine if once-daily colonic irrigation results in fecal continence for a 24-hour period in dogs with colostomies and if colonic volume increased in response to the irrigation. A prospective controlled experimental study. Four intact male and one intact female mixed breed dogs. All dogs received left end-on paralumbar colostomies. Four dogs received once-daily colonic irrigation for 8 weeks, whereas the control dog did not. Daily fecal weights were recorded for the length of the study in all dogs. Barium enema studies and volumetric studies were used to determine colonic volumes. Daily fecal weights were significantly decreased in treatment dogs compared with the control dog. Colonic volume increased in irrigated dogs in response to daily irrigation over the 8 week period of the study. Colonic irrigation resulted in significantly decreased fecal production over a 24-hour period. Therefore management of dogs with colostomies would be more practical and cost effective. It did not result in complete fecal continence in this study. Further clinical studies are indicated to determine if longer periods of irrigation would result in complete continence.

Exploring indicators of use of costly health services in community-dwelling adults with multiple chronic conditions.

PubMed

Holland, Diane E; Vanderboom, Catherine E; Lohse, Christine M; Mandrekar, Jay; Targonski, Paul V; Madigan, Elizabeth; Powell, Suzanne K

2015-01-01

Although experts recognize that including patient functional and social variables would improve models predicting risk of using costly health services, these self-reported variables are not widely used. Explore differences in predisposing characteristics, enabling resources, patient-perceived need for care and professionally evaluated need for care variables between patients receiving primary care within a Health Care Home who did and did not use hospital, emergency department, or skilled nursing facility services in a 3-month period of time. Primary care. Guided by the Behavioral Model of Health Service Use, a secondary analysis was conducted on data from a study that included 57 community-dwelling older adults receiving primary care in a Health Care Home. Because of the exploratory nature of the study, group differences in the use of costly care services were compared at the 0.10 level of statistical significance. Seventeen patients (29.8%) experienced costly care services. The greatest number of differences in variables between groups was in the category of patient-perceived need for care (functional impairments, dependencies, difficulties). Targeting case management services using evidence-based decision support tools such as prediction models enhances the opportunity to maximize outcomes and minimize waste of resources. Patient-perceived and clinician-evaluated need for care may need to be combined to fully describe the contextual needs that drive the use of health services. Difficulty with Activities with Daily Living and Instrumental Activities of Daily Living should be considered in future studies as candidate predictor variables for need for case management services in primary care settings.

Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial.

PubMed

Rafiq, Sulman; Johansson, Pär Ingemar; Zacho, Mette; Stissing, Trine; Kofoed, Klaus; Lilleør, Nikolaj Bang; Steinbrüchel, Daniel Andreas

2012-04-27

Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively. This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery. The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy. Clinicaltrials.gov Identifier NCT01046942.

Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects.

PubMed

Dooley, Kelly E; Sayre, Patrick; Borland, Julie; Purdy, Elizabeth; Chen, Shuguang; Song, Ivy; Peppercorn, Amanda; Everts, Stephanie; Piscitelli, Stephen; Flexner, Charles

2013-01-01

Cotreatment of tuberculosis (TB) and HIV among coinfected patients is now the standard of care. Rifampin (RIF) is a standard part of TB treatment but is a potent inducer of drug metabolizing enzymes. This study evaluated the effect of RIF or rifabutin (RBT) on the pharmacokinetics of the investigational HIV integrase inhibitor, dolutegravir (DTG). Phase I pharmacokinetic drug interaction study. In arm 1, healthy subjects received 50 mg of DTG once daily for 7 days (period 1), then 50 mg of DTG twice daily for 7 days (period 2), then 50 mg of DTG twice daily together with 600 mg of RIF once daily for 14 days (period 3). In arm 2, subjects received 50 mg of DTG once daily for 7 days (period 1) then 50 mg of DTG once daily together with 300 mg of RBT once daily for 14 days (period 2). PK sampling was performed at the end of each period. In arm 1, comparing period 3 to period 1, the geometric mean ratio (GMR) for the 24-hour area under the time-concentration curve (AUC0-24) was 1.33 [90% confidence interval (CI): 1.14 to 1.53], and the GMR for the trough (Cτ) was 1.22 (90% CI: 1.01 to 1.48). Comparing period 2 to period 1 in arm 2, the GMR for the AUC0-24 was 0.95 (90% CI: 0.82 to 1.10), and the GMR for the Cτ was 0.70 (90% CI: 0.57 to 0.87). Regimens including twice-daily DTG and RIF or once-daily DTG and RBT may represent a new treatment option for patients who require concomitant treatment of HIV and TB.

Captopril as a replacement for multiple therapy in hypertension: a controlled study.

PubMed

Yodfat, Y; Fidel, J; Bloom, D S

1985-11-01

A controlled study was conducted in hypertensive patients to investigate whether captopril can be substituted for the various other antihypertensive drugs (not including diuretics) to reduce side effects and improve the quality of life. Captopril in a twice daily dose of 25-50 mg, was substituted and titrated in 54 patients. Fifty-two patients, matched by age and sex, comprised the control group, and were treated with a variety of agents. During a follow-up of 9 months, 44 of the patients receiving captopril (81%) achieved the goal of supine blood pressure less than 90 mmHg. Captopril was discontinued in two patients due to side effects. Mild proteinuria was observed in two patients. A significant reduction in scores or rates of side effects (numbness, blurred vision, insomnia, vivid dreams, cold extremities, sleepiness, sexual dysfunction and fatigue) and improvement in quality of life (general feeling, mood and concentration) was observed in the study group compared with the control group. Captopril alone in a twice daily dose of 25-50 mg, or in co-treatment with thiazide, provided sustained blood pressure control with minimal side effects and improvement in quality of life compared with the treatment of hypertension with beta-blockers, vasodilators or methyldopa.

Telemedicine Support Groups for Home Parenteral Nutrition Users.

PubMed

Nelson, Eve-Lynn; Yadrich, Donna Macan; Thompson, Noreen; Wright, Shawna; Stone, Kathaleen; Adams, Natasia; Werkowitch, Marilyn; Smith, Carol E

2017-12-01

Patients receiving home parenteral nutrition (HPN), a life-sustaining intravenous (IV) infusion that provides nourishment and hydration to patients with short gut or inflammatory bowel diseases, are often isolated and not in visual contact with peers or health providers. One completed clinical trial (Clinical Trials.gov NCT0190028) and 1 ongoing clinical trial (Clinical Trials.gov NCT02987569) are evaluating a mobile videoconferencing-delivered support group intervention for patients on HPN and their caregivers. This home-based telemedicine intervention uses encrypted tablet-based videoconferencing to connect multiple families in real time. The twice-daily IV regimen is challenging for patients who may experience infusion catheter-related bloodstream infections, difficulties with fatigue, loss of sleep, depressive disorders, and worry over the potential life-threatening side effects and the expenses of this therapy. Using secure telemedicine, the facilitated support group intervention aims to enhance HPN home care, daily functioning, and quality of life. The authors provide the rationale for the telemedicine approach with HPN users and caregivers. They provide "how-to" information about the content and process of the facilitated support group sessions via secure videoconferencing. They share lessons learned from the ongoing evaluation of the telemedicine approach.

Fatal interstitial lung disease associated with icotinib.

PubMed

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

2014-12-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment.

Fatal interstitial lung disease associated with icotinib

PubMed Central

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi

2014-01-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment. PMID:25590006

Does activity limitation predict discharge destination for postacute care patients?

PubMed

Chang, Feng-Hang; Ni, Pengsheng; Jette, Alan M

2014-09-01

This study aimed to examine the ability of different domains of activity limitation to predict discharge destination (home vs. nonhome settings) 1 mo after hospital discharge for postacute rehabilitation patients. A secondary analysis was conducted using a data set of 518 adults with neurologic, lower extremity orthopedic, and complex medical conditions followed after discharge from a hospital into postacute care. Variables collected at baseline include activity limitations (basic mobility, daily activity, and applied cognitive function, measured by the Activity Measure for Post-Acute Care), demographics, diagnosis, and cognitive status. The discharge destination was recorded at 1 mo after being discharged from the hospital. Correlational analyses revealed that the 1-mo discharge destination was correlated with two domains of activity (basic mobility and daily activity) and cognitive status. However, multiple logistic regression and receiver operating characteristic curve analyses showed that basic mobility functioning performed the best in discriminating home vs. nonhome living. This study supported the evidence that basic mobility functioning is a critical determinant of discharge home for postacute rehabilitation patients. The Activity Measure for Post-Acute Care-basic mobility showed good usability in discriminating home vs. nonhome living. The findings shed light on the importance of basic mobility functioning in the discharge planning process.

Quality Indicators for Human Milk Use in Very Low Birthweight Infants: Are We Measuring What We Should be Measuring?

PubMed Central

Bigger, Harold R.; Fogg, Louis J.; Patel, Aloka; Johnson, Tricia; Engstrom, Janet L.; Meier, Paula P.

2014-01-01

Objective The objective of this study was to compare the currently used human milk (HM) quality indicators that measure whether very low birthweight (VLBW; <1500 g birthweight) infants “ever” received HM and whether they were still receiving HM at discharge from the neonatal intensive care unit (NICU) to the actual amount and timing of HM received. Study Design This study used data from a large NIH-funded cohort study and calculated whether VLBW infants ever received HM (HM-Ever) and of these infants, the percentage who were still receiving HM at NICU discharge (HM-DC). Then, the HM-DC indicator (exclusive, partial and none) was compared with the amount and timing of HM feedings received by these same infants. Results Of the 291 VLBW infants who met inclusion criteria, 285 received some HM (HM-Ever = 98%). At NICU discharge (HM-DC), 24.2%, 15.1% and 60.7% were receiving exclusive, partial and no HM, respectively. Of the 60.7% infants with no HM-DC, some had received higher amounts of HM during the NICU hospitalization than infants categorized as exclusive and partial for HM-DC. Of the infants with no HM-DC, 76.8% and 59.7% had received exclusive HM during the Days 1–14 and Days 1–28 exposure periods, respectively. Conclusion The average daily dose (HM-DD; in mL/kg/d) and cumulative percentage (HM-PCT; as % of cumulative enteral intake) of HM feedings were sufficient to significantly reduce the risk of multiple morbidities, including late onset sepsis, necrotizing enterocolitis, neurocognitive delay and rehospitalization, in the majority of the VLBW infants who were discharged with no HM-DC. Quality indicators that focus on the amount and timing of HM feedings in the NICU should be added to the HM-Ever and HM-DC measures. PMID:24526005

Dietary vitamin K variability affects International Normalized Ratio (INR) coagulation indices.

PubMed

Couris, Rebecca; Tataronis, Gary; McCloskey, William; Oertel, Lynn; Dallal, Gerard; Dwyer, Johanna; Blumberg, Jeffrey B

2006-03-01

Changes in daily vitamin K intake may contribute to marked variations in the International Normalized Ratio (INR) coagulation index in patients receiving oral warfarin anticoagulant therapy, with potentially serious adverse outcomes. Thus, patients receiving warfarin therapy are routinely counseled regarding this drug-nutrient interaction and are instructed to maintain consistent vitamin K intakes, though little quantitative information about this relationship is available. To determine the quantitative impact of variability in dietary vitamin K(1) (phylloquinone) intake, assessed by a validated patient self-monitoring instrument, on weekly INR in patients receiving warfarin anticoagulant therapy. A prospective dietary assessment study was conducted at the Massachusetts General Hospital in Boston. Sixty outpatients (37 males and 23 females) were selected with a mean age 60.3 +/- 16.8 years, who began oral warfarin anticoagulant therapy within 14 days prior to their first clinic visit to an outpatient anticoagulation therapy unit. Exclusion criteria included more than 2 drinks of alcohol per day, inability to speak English, and concurrent disease states affecting warfarin therapy such as liver disease and terminal illness. Over the five-week study period, participants recorded daily intakes in specified amounts of all food items appearing on a validated dietary self-assessment tool. Concomitant use of prescription and/or non-prescription medications was also obtained. Concurrent daily warfarin dose and adherence to the drug regimen, concomitant use of prescription and/or non-prescription medications known to interact with warfarin, and weekly INR were obtained. Week-to-week changes in vitamin K intake, warfarin dose, and INR were determined and cross-correlated. Forty-three patients (28 males and 15 females) completed the study and 17 dropped out. Pearson's correlation coefficient revealed the variability in INR and changes in vitamin K intake were inversely correlated (r = -0.600, p < 0.01). Multiple regression analysis (r = 0.848) indicated that a weekly change of 714 mug dietary vitamin K significantly altered weekly INR by 1 unit (p < 0.01) and a weekly change of 14.5 mg warfarin significantly altered weekly INR by 1 unit (p < 0.01) after adjustment for age, sex, weight, height, and concomitant use of medications known to interact with warfarin. Patients taking warfarin and consuming markedly changing amounts of vitamin K may have a variable weekly INR with potentially unstable anticoagulant outcomes.

Modeling Errors in Daily Precipitation Measurements: Additive or Multiplicative?

NASA Technical Reports Server (NTRS)

Tian, Yudong; Huffman, George J.; Adler, Robert F.; Tang, Ling; Sapiano, Matthew; Maggioni, Viviana; Wu, Huan

2013-01-01

The definition and quantification of uncertainty depend on the error model used. For uncertainties in precipitation measurements, two types of error models have been widely adopted: the additive error model and the multiplicative error model. This leads to incompatible specifications of uncertainties and impedes intercomparison and application.In this letter, we assess the suitability of both models for satellite-based daily precipitation measurements in an effort to clarify the uncertainty representation. Three criteria were employed to evaluate the applicability of either model: (1) better separation of the systematic and random errors; (2) applicability to the large range of variability in daily precipitation; and (3) better predictive skills. It is found that the multiplicative error model is a much better choice under all three criteria. It extracted the systematic errors more cleanly, was more consistent with the large variability of precipitation measurements, and produced superior predictions of the error characteristics. The additive error model had several weaknesses, such as non constant variance resulting from systematic errors leaking into random errors, and the lack of prediction capability. Therefore, the multiplicative error model is a better choice.

A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer.

PubMed

Park, K H; Lee, S; Park, J H; Kang, S Y; Kim, H Y; Park, I H; Park, Y H; Im, Y H; Lee, H J; Park, S; Lee, S I; Jung, K H; Kim, Y S; Seo, Jae Hong

2017-02-01

This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 μg/m 2 /day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm 3 and 161.75/mm 3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.

Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension

PubMed Central

Naidu, M; Usha, P; Rao, T; Shobha, J

2000-01-01

Angiotensin converting enzyme (ACE) inhibitors and dihydropyridine calcium antagonists are well established and widely used as monotherapy in patients with mild to moderate essential hypertension. Earlier studies combining short acting drugs from these classes require multiple dosing and were associated with poor compliance. Availability of longer acting compounds allows once daily administration to avoid the inconvenience of a multiple daily dose. It was decided to perform a randomised double blind, crossover study with the long acting calcium channel blocker amlodipine and the long acting ACE inhibitor lisinopril, given either alone or in combination in essential hypertension. Twenty four patients with diastolic blood pressure (DBP) between 95 and 104 mm Hg received amlodipine 2.5 mg and 5 mg, lisinopril 5 mg and 10 mg, and their combination as per a prior randomisation schedule. Supine and standing blood pressure and heart rate were recorded at weekly intervals. Higher doses of both the drugs individually or in combination were used if the target supine DBP below 90 mm Hg was not achieved. There was a significant additional blood pressure lowering effect with the combination when compared either with amlodipine or lisinopril alone. Five mg amlodipine and 10 mg lisinopril monotherapy achieved the target blood pressure in 71% and 72% patients respectively. The combination of 2.5 mg amlodipine with 5 mg lisinopril produced a much more significant lowering of blood pressure in a higher percentage of patients than that with an individual low dose.


Keywords: amlodipine; lisinopril; hypertension; combination therapy PMID:10824049

Twice-weekly aripiprazole for treating children and adolescents with tic disorder, a randomized controlled clinical trial.

PubMed

Ghanizadeh, Ahmad

2016-01-01

Treating tic disorder is challenging. No trial has ever examined whether twice weekly aripiprazole is effective for treating tic disorders. Participants of this 8-week randomized controlled parallel-group clinical trial were a clinical sample of 36 children and adolescents with tic disorder. Yale global tic severity scale was used to assess the outcome. Both groups received daily dosage of aripiprazole for the first 14 days. Then, one group received daily dose of aripiprazole while the other group received twice weekly dosage of aripiprazole for the next 46 days. The patients were assessed at baseline, week 2, 4, and 8. Tic scores decreased in both group significantly 22.8 (18.5) versus 22.0 (11.6). Moreover, there was no between group difference. The final mean (SD) score of motor and vocal tics in the group treated with daily treatment was not significantly different from the twice weekly group (Cohen's d = 0.36). The odds ratios for sedation and increased appetite were 3.05 and 3, respectively. For the first time, current findings support that twice weekly aripiprazole efficacy was not different from that of daily treatment. The rate of drowsiness in the twice weekly treatment group was less than that of the daily treatment group. This trial was registered at http://www.irct.ir. The registration number of this trial was: IRCT201312263930N32. http://www.irct.ir/searchresult.php?id=3930&number=32.

A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease.

PubMed

Olaosebikan, Rasaq; Ernest, Kolade; Bojang, Kalifa; Mokuolu, Olugbenga; Rehman, Andrea M; Affara, Muna; Nwakanma, Davis; Kiechel, Jean-René; Ogunkunle, Taofik; Olagunju, Tope; Murtala, Rukayat; Omefe, Peter; Lambe, Tosin; Bello, Surajudeen; Ibrahim, Olayinka; Olorunsola, Benedict; Ojuawo, Ayotade; Greenwood, Brian; Milligan, Paul

2015-08-15

Malaria prophylaxis is recommended for persons with sickle cell disease (SCD), but the value of this has been questioned. The aim of this study was to find out whether intermittent preventive treatment (IPT) with a fixed-dose combination of mefloquine-artesunate (MQAS) or sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) was more effective than daily proguanil for malaria prevention in subjects with SCD. Patients with SCD were randomized to receive daily treatment with proguanil or IPT with either MQAS or SPAQ once every 2 months at routine clinic visits. Patients were followed up for 14 months. A total of 270 patients with SCD were studied, with 90 in each group. Adherence to the IPT regimens was excellent, but 57% of patients took <75% of their daily doses of proguanil. IPT was well tolerated; the most common side effects were vomiting and abdominal pain. Protective efficacy against malaria, compared with daily proguanil, was 61% (95% confidence interval, 3%-84%) for MQAS and 36% (40%-70%) for SPAQ. There were fewer outpatient illness episodes in children who received IPT than those who received proguanil. IPT with MQAS administered to patients with SCD during routine clinic visits was well tolerated and more effective in preventing malaria than daily prophylaxis with proguanil. NCT01319448 and ISRCTN46158146. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial.

PubMed

Prajna, N Venkatesh; Krishnan, Tiruvengada; Rajaraman, Revathi; Patel, Sushila; Srinivasan, Muthiah; Das, Manoranjan; Ray, Kathryn J; O'Brien, Kieran S; Oldenburg, Catherine E; McLeod, Stephen D; Zegans, Michael E; Porco, Travis C; Acharya, Nisha R; Lietman, Thomas M; Rose-Nussbaumer, Jennifer

2016-12-01

To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. The Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis. Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. The primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use. A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some suggestion that Fusarium species might have a decreased rate of perforation or TPK in the oral voriconazole-treated arm; however, this was not a statistically significant finding after Holms-Šidák correction for multiple comparisons (effect coefficient, 0.49; 95% CI, 0.26-0.92; P = .03). Patients receiving oral voriconazole experienced a total of 58 adverse events (48.7%) compared with 28 adverse events (23.1%) in the placebo group (P < .001 after Holms-Šidák correction for multiple comparisons). There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. All patients in this study were enrolled in India and Nepal; therefore, it is possible that organisms in this region may exhibit characteristics different from those in other regions of the world. clinicaltrials.gov Identifier: NCT00996736.

Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial.

PubMed

Sang, Zhongna; Wang, Peizhong Peter; Yao, Zhaixiao; Shen, Jun; Halfyard, Beth; Tan, Long; Zhao, Na; Wu, Yuntang; Gao, Shuo; Tan, Jian; Liu, Jiayu; Chen, Zupei; Zhang, Wanqi

2012-02-01

The beneficial health effects associated with Universal Salt Iodization are well known. Yet, little is known about the possible adverse health effects in people with high iodine intake and the safe daily intake upper limit in the Chinese population. The objective of this study was to explore the safe upper level of total daily iodine intake among adults in China. A 4-wk, double-blind, placebo-controlled, randomized controlled trial was conducted in 256 euthyroid adults. Participants were randomly assigned to 12 intervention groups with various iodine supplement doses ranging from 0 to 2000 μg/d. Total iodine intake included iodine from both supplements and diet. Multiple outcome measures were used to evaluate possible adverse effects, including thyroid function, thyroid size, and urinary iodine. The mean iodine intake from the diets and salt intake of the participants were 105 ± 25 and 258 ± 101 μg/d, respectively. In comparison with the placebo group, all iodide-supplemented groups responded with significant increases in median urinary iodine concentrations (P < 0.05) and in thyroid-stimulating hormone concentration (P < 0.05). Thyroid volume decreased after 4 wk in the high-iodine intervention groups (1500-2000 μg). Subclinical hypothyroidism appeared in the groups that received 400 μg I (5%) and 500-2000 μg I (15-47%). This study showed that subclinical hypothyroidism appeared in the participants who took the 400-μg I supplement, which provided a total iodine intake of ∼800 μg/d. Thus, we caution against a total daily iodine intake that exceeds 800 μg/d in China and recommend further research to determine a safe daily upper limit.

Phase 1 and Pharmacokinetic Drug-Drug Interaction Study of Metformin, Losartan, and Linagliptin Coadministered With DW1029M in Healthy Volunteers.

PubMed

Moon, Seol Ju; Kim, Sun-Young; Lim, Cheol-Hee; Jang, Hwan Bong; Kim, Min-Gul; Jeon, Ji-Young

2017-07-01

We investigated botanical drug-pharmaceutical drug interactions between DW1029M (a botanical extract of Morus alba linne root bark and Puerariae radix) and metformin, losartan, and linagliptin in the steady state. Three studies were conducted as randomized, open-label, 2-period, 2-treatment, multiple-dose, 2-way crossover designs. Eligible subjects received metformin (500 mg twice daily), losartan (50 mg once daily), or linagliptin (5 mg once daily) with DW1029M (300 mg × 2T twice daily) every 12 hours on days 1 through 6 and a single dose on the morning of day 7. Coadministration of DW1029M with metformin, losartan, or linagliptin had no clinically relevant effects based on the area under the plasma concentration-time curve (AUC τ ) geometric least-squares mean ratio (GMR) - AUC τ GMR, 89.7; 90% confidence interval (CI), 81.0-99.4 for metformin; AUC τ GMR, 96.2; 90%CI, 86.3-107.1 for losartan; and AUC τ GMR, 89.7; 90%CI, 83.2-96.6 for linagliptin. In addition, coadministration of DW1029M did not have any clinically meaningful effect on the maximum plasma concentration (C max,ss ) - C max,ss GMR, 87.3; 90%CI, 76.2-100.0 for metformin; C max,ss GMR, 90.5; 90%CI, 78.3-104.6 for losartan; and C max,ss GMR, 81.4; 90%CI, 69.5-95.3 for linagliptin. Coadministration of DW1029M with metformin, losartan, or linagliptin was well tolerated. © 2016, The American College of Clinical Pharmacology.

Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial.

PubMed

Bowen, Asha C; Tong, Steven Y C; Andrews, Ross M; O'Meara, Irene M; McDonald, Malcolm I; Chatfield, Mark D; Currie, Bart J; Carapetis, Jonathan R

2014-12-13

Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting. In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291. Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine benzylpenicillin. Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered. Australian National Health and Medical Research Council. Copyright © 2014 Elsevier Ltd. All rights reserved.

Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial.

PubMed

Davies, M; Lavalle-González, F; Storms, F; Gomis, R

2008-05-01

For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose < or =100 mg/dl (< or =5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A(1c) (HbA(1c)). Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA(1c) decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (-1.4%, p < 0.001; algorithm 1 -1.3% vs. algorithm 2 -1.5%; p = 0.03) and glargine plus >1 OAD (-1.7%, p < 0.001; algorithm 1 -1.5% vs. algorithm 2 -1.8%; p = 0.001). This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA(1c) with a low risk of hypoglycaemia. The greater reduction in HbA(1c) was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD.

Can Diastat Grafts Meet the Challenges of Daily Punctures?

PubMed

Chandran, Prem K G; Messer, Diane; Sidwell, Richard A; Stubbs, David H; Nish, Andrew D

1997-01-01

To determine whether Diastat grafts can meet the challenges of daily needle punctures required for home hemodialysis (HD), a retrospective analysis was performed on the experience with 47 grafts placed in 44 patients receiving HD three times a week. The control group consisted of 17 patients who received 17 stretch polytetrafluoroethylene (s-PTFE) grafts. Apart from their ability to better contain bleeding after needle withdrawal, in all measures of longevity the Diastat grafts were outperformed by the s-PTFE grafts. No more direct data exist to address the original challenge.

Effect of fluid and salt supplements in preventing the development of "osteopenia" in hypokinetic rats

NASA Astrophysics Data System (ADS)

Zorbas, Y. G.; Federenko, Y. F.; Togawa, M. N.

It has been suggested that a daily intake of fluid and salt supplements may be used to prevent bone demineralization in human subjects after prolonged exposure to hypokinesia (diminished muscular activity). Thus, the objective of this investigation was to evaluate the effect of fluid and salt supplementation in the prevention of development of osteoporosis in 64 Wistar rats with an initial body weight of 339-345 g, after exposure to 90 days of hypokinesia. They divided into 4 equal groups: the first group of rats placed under ordinary vivarium conditions and served as vivarium control; the second group were also placed under ordinary vivarium conditions but received daily fluid and salt supplements; the third group were subjected to pure hypokinesia, i.e. without the use of any preventive measures; and the fourth group were submitted to hypokinesia and received daily fluid and salt supplements. For the simulation of the hypokinetic effect the experimental group of rats were kept in small, individual, wooden cages. Through the experimental period the second and fourth group of rats received 8 ml/100 g body wt water and 5 ml 100 g body wt NaCl daily. By the end of the experimental period the animals were decapitated and the spongy matter of tibia and vertebrae of the rats were examined for changes referable to osteoporosis. It was found that the daily intake of fluid and salt supplements caused an increase in the volume density of primary spongiosa of bones. It was concluded that a daily intake of fluid and salt supplements may be used to prevent the development of osteoporosis in rats subjected to prolonged motor activity restriction.

Adaptive receiver structures for asynchronous CDMA systems

NASA Astrophysics Data System (ADS)

Rapajic, Predrag B.; Vucetic, Branka S.

1994-05-01

Adaptive linear and decision feedback receiver structures for coherent demodulation in asynchronous code division multiple access (CDMA) systems are considered. It is assumed that the adaptive receiver has no knowledge of the signature waveforms and timing of other users. The receiver is trained by a known training sequence prior to data transmission and continuously adjusted by an adaptive algorithm during data transmission. The proposed linear receiver is as simple as a standard single-user detector receiver consisting of a matched filter with constant coefficients, but achieves essential advantages with respect to timing recovery, multiple access interference elimination, near/far effect, narrowband and frequency-selective fading interference suppression, and user privacy. An adaptive centralized decision feedback receiver has the same advantages of the linear receiver but, in addition, achieves a further improvement in multiple access interference cancellation at the expense of higher complexity. The proposed receiver structures are tested by simulation over a channel with multipath propagation, multiple access interference, narrowband interference, and additive white Gaussian noise.

A Multicenter, Randomized, Open-Label, Pharmacokinetics and Safety Study of Pantoprazole Tablets in Children and Adolescents Aged 6 Through 16 Years With GERD

PubMed Central

Ward, Robert M.; Kearns, Gregory L.; Tammara, Brinda; Bishop, Phyllis; O’Gorman, Molly A.; James, Laura P.; Katz, Mitchell H.; Maguire, Mary K.; Rath, Natalie; Meng, Xu; Comer, Gail M.

2011-01-01

SUMMARY Children with GERD may benefit from gastric acid suppression with proton pump inhibitors such as pantoprazole. Effective treatment with pantoprazole requires correct dosing and understanding of the drug’s kinetic profile in children. The aim of these studies was to characterize the pharmacokinetic (PK) profile of single and multiple doses of pantoprazole delayed-release tablets in pediatric patients with GERD aged ≥6 through 11 years (study 1) and 12 through 16 years (study 2). Patients were randomly assigned to receive pantoprazole 20 or 40 mg once daily. Plasma pantoprazole concentrations were obtained at intervals through 12 hours after the single dose, and at 2 and 4 hours after multiple doses for PK evaluation. PK parameters were derived by standard noncompartmental methods and examined as a function of both drug dose and patient age. Safety was also monitored. Pantoprazole PK was dose independent (when dose normalized) and similar toPK reported from adult studies. There was no evidence of accumulation with multiple dosing or reports of serious drug-associated adverse events. In children aged 6 to 16 years with GERD, currently available pantoprazole delayed-release tablets can be used to provide systemic exposure similar to that in adults. PMID:20852004

The effect of a school-based active commuting intervention on children's commuting physical activity and daily physical activity.

PubMed

McMinn, David; Rowe, David A; Murtagh, Shemane; Nelson, Norah M

2012-05-01

To investigate the effect of a school-based intervention called Travelling Green (TG) on children's walking to and from school and total daily physical activity. A quasi-experiment with 166 Scottish children (8-9 years) was conducted in 2009. One group (n=79) received TG and another group (n=87) acted as a comparison. The intervention lasted 6 weeks and consisted of educational lessons and goal-setting tasks. Steps and MVPA (daily, a.m. commute, p.m. commute, and total commute) were measured for 5 days pre- and post-intervention using accelerometers. Mean steps (daily, a.m., p.m., and total commute) decreased from pre- to post-intervention in both groups (TG by 901, 49, 222, and 271 steps/day and comparison by 2528, 205, 120, and 325 steps/day, respectively). No significant group by time interactions were found for a.m., p.m., and total commuting steps. A medium (partial eta squared=0.09) and significant (p<0.05) group by time interaction was found for total daily steps. MVPA results were similar to step results. TG has a little effect on walking to and from school. However, for total daily steps and daily MVPA, TG results in a smaller seasonal decrease than for children who do not receive the intervention. Copyright © 2012 Elsevier Inc. All rights reserved.

Indoor and Outdoor Context-Specific Contributions to Early Adolescent Moderate to Vigorous Physical Activity as Measured by Combined Diary, Accelerometer, and GPS.

PubMed

Pearce, Matthew; Saunders, David H; Allison, Peter; Turner, Anthony P

2018-01-01

The distribution of adolescent moderate to vigorous physical activity (MVPA) across multiple contexts is unclear. This study examined indoor and outdoor leisure time in terms of being structured or unstructured and explored relationships with total daily MVPA. Between September 2012 and January 2014, 70 participants (aged 11-13 y) from 4 schools in Edinburgh wore an accelerometer and global positioning system receiver over 7 days, reporting structured physical activity using a diary. Time spent and MVPA were summarized according to indoor/outdoor location and whether activity was structured/unstructured. Independent associations between context-specific time spent and total daily MVPA were examined using a multivariate linear regression model. Very little time or MVPA was recorded in structured contexts. Unstructured outdoor leisure time was associated with an increase in total daily MVPA almost twice that of unstructured indoor leisure time [b value (95% confidence interval), 8.45 (1.71 to 14.48) vs 4.38 (0.20 to 8.22) minute increase per hour spent]. The association was stronger for time spent in structured outdoor leisure time [35.81 (20.60 to 52.27)]. Research and interventions should focus on strategies to facilitate time outdoors during unstructured leisure time and maximize MVPA once youth are outdoors. Increasing the proportion of youth engaging in structured activity may be beneficial given that, although time spent was limited, association with MVPA was strongest.

Water-quality characteristics of urban runoff and estimates of annual loads in the Tampa Bay area, Florida, 1975-80

USGS Publications Warehouse

Lopez, M.A.; Giovannelli, R.F.

1984-01-01

Rainfall, runoff, and water quality data were collected at nine urban watersheds in the Tampa Bay area from 1975 to 1980. Watershed drainage area ranged from 0.34 to 0.45 sq mi. Land use was mixed. Development ranged from a mostly residential watershed with a 19% impervious surface, to a commercial-residential watershed with a 61% impervious surface. Average biochemical oxygen demand concentrations of base flow at two sites and of stormwater runoff at five sites exceeded treated sewage effluent standards. Average coliform concentrations of stormwater runoff at all sites were several orders of magnitude greater than standards for Florida Class III receiving water (for recreation or propagation and management of fish and wildlife). Average concentrations of lead and zinc in stormwater runoff were consistently higher than Class III standards. Stormwater-runoff loads and base-flow concentrations of biochemical oxygen demand, chemical oxygen demand, total nitrogen, total organic nitrogen, total phosphorus, and lead were related to runoff volume, land use, urban development, and antecedent daily rainfall by multiple linear regression. Stormwater-runoff volume was related to pervious area, hydraulically connected impervious surfaces, storm rainfall, and soil-infiltration index. Base-flow daily discharge was related to drainage area and antecedent daily rainfall. The flow regression equations of this report were used to compute 1979 water-year loads of biochemical oxygen demand, chemical oxygen demand, total nitrogen, total organic nitrogen, total phosphorus , and total lead for the nine Tampa Bay area urban watersheds. (Lantz-PTT)

Protocol for the CONVERT trial-Concurrent ONce-daily VErsus twice-daily RadioTherapy: an international 2-arm randomised controlled trial of concurrent chemoradiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small cell lung cancer (LS-SCLC) and good performance status.

PubMed

Faivre-Finn, Corinne; Falk, Sally; Ashcroft, Linda; Bewley, Michelle; Lorigan, Paul; Wilson, Elena; Groom, Nicki; Snee, Michael; Fournel, Pierre; Cardenal, Felipe; Bezjak, Andrea; Blackhall, Fiona

2016-01-20

Concurrent ONce-daily VErsus twice-daily RadioTherapy (CONVERT) is the only multicentre, international, randomised, phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy (RT) in limited stage small cell lung cancer (LS-SCLC). Following on from the Turrisi trial of once-daily versus twice-daily (BD) concurrent chemoradiotherapy, there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily radiation dose. This trial has the potential to define a new standard chemo-RT regimen for patients with LS-SCLC and good performance status. 447 patients with histologically or cytologically proven diagnosis of SCLC were recruited from 74 centres in eight countries between 2008 and 2013. Patients were randomised to receive either concurrent twice-daily RT(45 Gy in 30 twice-daily fractions over 3 weeks) or concurrent once-daily RT(66 Gy in 33 once-daily fractions over 6.5 weeks) both starting on day 22 of cycle 1. Patients are followed up until death. The primary end point of the study is overall survival and secondary end points include local progression-free survival, metastasis-free survival, acute and late toxicity based on the Common Terminology Criteria for Adverse Events V.3.0, chemotherapy and RTdose intensity. The trial received ethical approval from NRES Committee North West-Greater Manchester Central (07/H1008/229). There is a trial steering committee, including independent members and an independent data monitoring committee. Results will be published in a peer-reviewed journal and presented at international conferences. ISRCTN91927162; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Comparative study on treatment satisfaction and health perception in children and adolescents with type 1 diabetes mellitus on multiple daily injection of insulin, insulin pump and sensor-augmented pump therapy.

PubMed

Hussain, Tara; Akle, Mariette; Nagelkerke, Nico; Deeb, Asma

2017-01-01

Diabetes management imposes considerable demands on patients. Treatment method used has an impact on treatment satisfaction. We aim to examine the relationship between treatment satisfaction and health perception with the method used for treatment of type 1 diabetes mellitus in children and adolescents. We have interviewed patients with type 1 diabetes mellitus using questionnaires to assess treatment satisfaction and health perception. Patients were divided into three groups based on treatment used: multiple daily injection, insulin pump and sensor-augmented pump therapy. Comparison of scores was done between the groups. A total of 72 patients were enrolled (36 males). Mean age (standard deviation) was 11.4 (4.4) years and duration of diabetes of 4.9 (3.5) years. Mean (standard deviation) HbA1c was 8.1 (1.2). Median (range) duration of sensor use was 17.7 (3-30) days/month. Mean scale for treatment satisfaction and health perception questions was 25.3, 29.7 and 31.7 and 60, 79.7 and 81 for the multiple daily injection, pump and sensor-augmented pump, respectively (p = 0.00). Significant difference was seen between the multiple daily injection and both other groups. Sensor-augmented pump group scored higher than the pump group. However, the difference was not statistically significant. Duration of sensor use showed no correlation with treatment satisfaction. The method used for diabetes treatment has an impact on patients' satisfaction and health perception in children and adolescents with type 1 diabetes mellitus. Insulin pump users have a higher treatment satisfaction and better health perception than those on multiple daily injection. Augmenting pump therapy with sensor use adds value to treatment satisfaction without correlation with the duration of the sensors use.

The Combined Effects of Daily Stressors and Major Life Events on Daily Subjective Ages.

PubMed

Bellingtier, Jennifer A; Neupert, Shevaun D; Kotter-Grühn, Dana

2017-07-01

Stressors may be a contributing factor in determining how old an individual feels, looks, or would like to be. Currently, little research has been devoted to understanding the relationship between stressors and subjective age in older adults. We focus on the combined impact of major life-event stressors and daily stressors on multiple indicators of subjective age: felt age, ideal age, and look age. Furthermore, we examine the process by which daily stressors relate to subjective ages by testing whether positive affect, control, and negative affect mediate this relationship. Using a daily-diary design, the current study measured older adults' (60-96 years old) stressors, subjective ages, personal control, and affect. Felt, ideal, and look ages each demonstrated a unique pattern of interactions between daily stressors and major life-event stressors. Furthermore, our findings suggest that on the daily level, the relationship between stressors and felt age is mediated by negative affect but not by control and positive affect. Findings indicate the need to consider the broader contextual picture of stressors, as well as their differential impact on multiple indicators of subjective age. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration.

PubMed

Calcagno, A; Pinnetti, C; De Nicolò, A; Scarvaglieri, E; Gisslen, M; Tempestilli, M; D'Avolio, A; Fedele, V; Di Perri, G; Antinori, A; Bonora, S

2018-06-01

Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive patients taking abacavir once daily and twice daily, respectively. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml -1 , P = 0.038 and 123 vs. 49 ng ml -1 , P = 0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once-daily treatment. © 2018 The British Pharmacological Society.

Health, Social, and Economic Outcomes Experienced by Families as a Result of Receiving Assistance from a Community-Based Diaper Bank.

PubMed

Massengale, Kelley E C; Erausquin, Jennifer Toller; Old, Michelle

2017-10-01

Objectives This paper aims to describe low-income recipients of a community-based diaper bank and the multiple daily challenges they face. Our paper seeks to document the health, social, and financial outcomes recipients experienced after receiving assistance. Methods We surveyed families (n = 150) about their experiences receiving diapers from a diaper bank in the southeastern United States. Additionally, we conducted short, focused interviews with families (n = 15) about outcomes after receiving diapers. Results Families experience regularly a range of challenges meeting basic needs. These difficulties include high unmet needs for transportation, food, and nonfood essentials such as personal hygiene items. Families experiencing the greatest difficulty in paying utility or medical bills were significantly more likely to have a high level of diaper need compared to families facing these challenges less often (AORs ranging from 3.40 to 9.39). As a result of receiving diapers, families reported positive health, social, and economic outcomes. Families reported positive changes in parental mood; improved child health and happiness; increased opportunities for childcare, work, and school attendance; and the ability to divert household finances toward other basic needs, including utilities and medical care. Conclusions for Practice The monetary value of the supplemental provision of diapers is a small investment in affected families' economic, social, and health outcomes. The positive effects continue far longer than the diapers provided. We demonstrate the social value of such an operation, and recommend the expansion of federal, state, and local safety net programs to help low-income families secure a steady supply of diapers.

Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

PubMed

Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

2017-03-09

A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10 6 hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4 th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that the healed ribs were stiffer than intact ribs in torsion, compression, and bending simulations, as expected when examining bone callus composed of woven bone. Administration of both hMSCs and PTH worked synergistically in rib fracture healing, suggesting this approach may pave the way to treat multiple rib fractures as well as additional fractures in various anatomical sites.

Intermittent oral iron supplementation during pregnancy (Review)

PubMed Central

Peña-Rosas, Juan Pablo; De-Regil, Luz Maria; Dowswell, Therese; Viteri, Fernando E

2014-01-01

Background Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs of both the mother and the fetus. Traditionally, gestational anaemia has been prevented with the provision of daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. one, two or three times a week on non-consecutive days) supplementation with iron alone or in combination with folic acid or other vitamins and minerals has recently been proposed as an alternative to daily supplementation. Objectives To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (23 March 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) for ongoing studies and contacted relevant organisations for the identification of ongoing and unpublished studies (23 March 2012). Selection criteria Randomised or quasi-randomised trials. Data collection and analysis We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy. Main results This review includes 21 trials from 13 different countries, but only 18 trials (with 4072 women) reported on our outcomes of interest and contributed data to the review. All of these studies compared daily versus intermittent iron supplementation. Three studies provided iron alone, 12 iron+folic acid and three more iron plus multiple vitamins and minerals. Their methodological quality was mixed and most had high levels of attrition. Overall, there was no clear evidence of differences between groups for infant primary outcomes: low birthweight (average risk ratio (RR) 0.96; 95% confidence interval (CI) 0.61 to 1.52, seven studies), infant birthweight (mean difference MD −8.62 g; 95% CI −52.76 g to 35.52 g, eight studies), premature birth (average RR 1.82; 95% CI 0.75 to 4.40, four studies). None of the studies reported neonatal deaths or congenital anomalies. For maternal outcomes, there was no clear evidence of differences between groups for anaemia at term (average RR 1.22; 95% CI 0.84 to 1.80, four studies) and women receiving intermittent supplementation had less side effects (average RR 0.56; 95% CI 0.37 to 0.84, 11 studies) than those receiving daily supplements. Women receiving intermittent supplements were also at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.48; 95% CI 0.35 to 0.67, 13 studies). There were no significant differences in iron-deficiency anaemia between women receiving intermittent or daily iron+folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63, 1 study). There were no maternal deaths (six studies) or women with severe anaemia in pregnancy (six studies). None of the studies reported on iron deficiency at term or infections during pregnancy. Where sufficient data were available for primary outcomes, we set up subgroups to look for possible differences between studies in terms of earlier or later supplementation; women’s anaemia status at the start of supplementation; higher and lower weekly doses of iron; and the malarial status of the region in which the trials were conducted. There was no clear effect of these variables on the results of the review. Authors’ conclusions The present systematic review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation regimens in pregnant women on haematological and pregnancy outcomes. The findings suggest that intermittent iron+folic acid regimens produce similar maternal and infant outcomes at birth as daily supplementation but are associated with fewer side effects. Women receiving daily supplements had increased risk of developing high levels of Hb in mid and late pregnancy but were less likely to present mild anaemia near term. Although the evidence is limited and the quality of the trials was low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care. PMID:22786531

Role of Omega-3 Fatty Acids on Lipid Profile in Diabetic Dyslipidaemia: Single Blind, Randomised Clinical Trial.

PubMed

Chauhan, Shaylika; Kodali, Hanish; Noor, Jawad; Ramteke, Karuna; Gawai, Vidisha

2017-03-01

Diabetic dyslipidaemia is characterised by hypertriglyceridaemia, low High Density Lipoprotein (HDL), postprandial lipimea, small and dense LDL particles is considered to be a major predisposing factor for various macrovascular complications. Omega-3 fatty acids are fish oil derivative introduced in the market for dyslipidaemia associated with increased triglyceride level. To study the effect of omega-3 fatty acids on lipid profile in Type II diabetes patients. This study was prospective, single blind, randomized comparative trial. Hundred patients were randomized into three groups. Group I received metformin 500 mg twice daily and placebo, Group II received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) once daily and the Group III received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) twice daily. ANOVA test was applied for analysis. Group II was effective in reducing the triglyceride level from 144.59±14.18 mg/dl to 101±13.31 mg/dl which was significant as compared to Group I from 147.67±18.57 mg/dl to 145.8±19.86 mg/dl respectively. Group III containing 1 g of omega-3 fatty acids twice daily showed decrease from 144.83±22.17 mg/dl to 86±17.46 mg/dl and was more effective in reducing triglyceride levels than Group II containing 1 gram of omega-3 fatty acids once daily. Omega-3 fatty acids can be given in conjunction with metformin to reduce triglyceride levels in diabetic dyslipidaemia without any adverse drug reactions or any drug interaction. Omega-3 fatty acids were effective in reducing the triglyceride level significantly as compared to placebo. Two grams of omega-3 fatty acids were more effective than 1 gram of omega-3 fatty acids in reducing triglyceride levels.

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

PubMed Central

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-01-01

Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Infections during induction therapy for children with acute lymphoblastic leukemia. the role of sulfamethoxazole-trimethoprim (SMX-TMP) prophylaxis.

PubMed

Rungoe, Christine; Malchau, Emma Louise; Larsen, Line Nordahl; Schroeder, Henrik

2010-08-01

Bacteremias are frequent during induction therapy for acute lymphoblastic leukemia (ALL) in children. Antibacterial prophylaxis therapy may thus be warranted. The purpose of this study was to analyze the rate of infections during induction therapy in two cohorts of children with ALL where one cohort received prophylactic sulfamethoxazole-trimethoprim (SMX-TMP). All infections were registered through a retrospective non-randomized review of medical records of 171 consecutive children newly diagnosed with ALL below 15 years of age at diagnosis. A total of 85 children treated from 1992 to 2000 did not receive SMX-TMP, whereas 86 children treated from 2000 to 2008 received SMX-TMP 20 mg/kg in one daily oral dose during induction therapy. A total of 26% of all children had no febrile episodes during induction. Infections were more frequent in children below 5 years of age. Significantly fewer children receiving SMX-TMP developed fever (17% vs. 34%, P = 0.02) and bacteremia (20% vs. 45%, P = 0.0003). Especially children with non-high risk criteria had fewer infections when receiving prophylaxis. When adjusting for age, type of catheter, and SMX-TMP prophylaxis on the risk of bacteremia by a multiple Cox regression analysis, we found that age and prophylaxis, but not the type of catheter, were associated with a significantly reduced risk of bacteremia. Children with ALL receiving SMX-TMP prophylaxis during induction therapy experienced fewer febrile episodes, fewer days with fever demanding intravenous antibiotic treatment, and fewer episodes of bacteremia. Both SMX-TMP prophylaxis and age played significant independent roles for the occurrence of bacteremia. (c) 2010 Wiley-Liss, Inc.

Usual Dietary Intakes: SAS Macros for the NCI Method

Cancer.gov

SAS macros are currently available to facilitate modeling of a single dietary component, whether consumed daily or episodically; ratios of two dietary components that are consumed nearly every day; multiple dietary components, whether consumed daily or episodically.

Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir

PubMed Central

García-Lerma, J. Gerardo; Otten, Ron A; Qari, Shoukat H; Jackson, Eddie; Cong, Mian-er; Masciotra, Silvina; Luo, Wei; Kim, Caryn; Adams, Debra R; Monsour, Michael; Lipscomb, Jonathan; Johnson, Jeffrey A; Delinsky, David; Schinazi, Raymond F; Janssen, Robert; Folks, Thomas M; Heneine, Walid

2008-01-01

Background In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. Methods and Findings We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. Conclusions This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities. PMID:18254653

Pharmacokinetics and safety of vitamin E δ-tocotrienol after single and multiple doses in healthy subjects with measurement of vitamin E metabolites.

PubMed

Mahipal, Amit; Klapman, Jason; Vignesh, Shivakumar; Yang, Chung S; Neuger, Anthony; Chen, Dung-Tsa; Malafa, Mokenge P

2016-07-01

Vitamin E delta-tocotrienol (VEDT) has demonstrated chemopreventive and antineoplastic activity in preclinical models. The aim of our study was to determine the safety and pharmacokinetics of VEDT and its metabolites after single- and multiple-dose administrations in healthy subjects. Thirty-six subjects received from 100 to 1600 mg of oral VEDT as a single dose or twice daily for 14 consecutive days. A 3 + 3 dose escalation design was utilized. Pharmacokinetic data were derived from high-performance liquid chromatography (HPLC) assays. Serial blood and urine samples were collected before and during VEDT administration, with serum and urine metabolites assessed using HPLC. No drug-related adverse events were observed. Pharmacokinetic parameters for single and multiple doses were, respectively, as follows (shown as range): time to maximum concentration of 4-9.3 and 4.7-7.3 h, maximum concentration of 795.6-3742.6 and 493.3-3746 ng/mL, half-life of 1.7-5.9 and 2.3-6.9 h, and 0-12 h area under the curve of 4518.7-20,781.4 and 1987.7-22,171.2 ng h/mL. Plasma tocotrienols were significantly increased after VEDT administration, indicating oral bioavailability of VEDT in humans. Plasma and urine levels of metabolites, δ-carboxyethyl hydroxychroman, and δ-carboxymethylbutyl hydroxychroman were elevated after VEDT administration in a dose-dependent manner and were 30-60 times significantly higher than δ-tocotrienol levels. VEDT can be safely administered at doses up to 1600 mg twice daily. Plasma VEDT concentrations were comparable to those obtained in VEDT-treated mice in which tumor growth was delayed. Our results suggest that VEDT can be safely consumed by healthy subjects and achieve bioactive levels, supporting the investigation of VEDT for chemoprevention.

Oral supplementation with L‐homoarginine in young volunteers

PubMed Central

Atzler, Dorothee; Schönhoff, Mirjam; Cordts, Kathrin; Ortland, Imke; Hoppe, Julia; Hummel, Friedhelm C.; Gerloff, Christian; Jaehde, Ulrich; Jagodzinski, Annika; Böger, Rainer H.; Choe, Chi‐un

2016-01-01

Aims Low blood concentrations of the naturally occurring amino acid L‐homoarginine (L‐hArg) are related to impaired cardiovascular outcome and mortality in humans and animals. L‐hArg is a weak substrate of nitric oxide synthase and an inhibitor of arginases in vitro. The aim of our study was to obtain kinetic and dynamic data after oral L‐hArg supplementation. Methods In a double‐blind, randomized, placebo‐controlled crossover study, 20 young volunteers received 125 mg L‐hArg once daily for 4 weeks. Kinetic parameters (C max, T max and AUC0‐24h) were calculated after ingestion of single and multiple doses of oral supplementation as primary endpoint. Secondary endpoints that were evaluated were routine laboratory, L‐arginine, asymmetric dimethylarginine (ADMA), pulse wave velocity (PWV), augmentation index (AIx), flow‐mediated vasodilatation (FMD), corticospinal excitability, i.e. motor threshold (MT), and cortical excitability, i.e. intracortical inhibition (ICI) and facilitation (ICF). Results One hour after ingestion (T max), L‐hArg increased the baseline L‐hArg plasma concentration (2.87 ± 0.91 μmol l−1, mean ± SD) by 8.74 ± 4.46 [95% confidence intervals 6.65; 10.9] and 17.3 ± 4.97 [14.9; 19.6] μmol l−1 (C max), after single and multiple doses, respectively. Once‐only and 4 weeks of supplementation resulted in AUCs0‐24h of 63.5 ± 28.8 [50.0; 76.9] and 225 ± 78.5 [188; 2624] μmol l−1*h, for single and multiple doses, respectively. Routine laboratory parameters, L‐arginine, ADMA, PWV, AIx, FMD, MT, ICI and ICF did not change by L‐hArg supplementation compared to baseline. Conclusion Once daily orally applied 125 mg L‐hArg raises plasma L‐hArg four‐ and sevenfold after single dose and 4 weeks of supplementation, respectively, and is safe and well tolerated in young volunteers. PMID:27434056

Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development.

PubMed

Amory, J K; Anawalt, B D; Bremner, W J; Matsumoto, A M

2001-01-01

Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive gonadotropin levels between men achieving azoospermia and those with persistent spermatogenesis. This study, therefore, demonstrates that neither monthly nor daily differences in serum testosterone, or fluoroimmunoreactive or bioactive gonadotropins explain why some men fail to completely suppress their sperm counts to zero with weekly TE administration. Innate differences in the testicle's ability to maintain spermatogenesis in a low-gonadotropin environment may explain persistent spermatogenesis in some men treated with androgen-based contraceptive regimens.

Verbal communication of families with cancer patients at end of life: A questionnaire survey with bereaved family members.

PubMed

Nakazato, Kazuhiro; Shiozaki, Mariko; Hirai, Kei; Morita, Tatsuya; Tatara, Ryuhei; Ichihara, Kaori; Sato, Shinichi; Simizu, Megumi; Tsuneto, Satoru; Shima, Yasuo; Miyasita, Mitsunori

2018-01-01

To clarify the verbal communication of feelings between families and patients in Japanese palliative care units from the perspective of bereaved family members by examining (1) proportions of families' and patients' verbalization of six feelings (gratitude, love, seeking forgiveness, giving forgiveness, wishes after death, and continuing bonds), (2) recognition of receiving these feelings through verbalization from the family's perspective, and (3) the specific attitudes of family members that influence their verbalizations. In 2010, a cross-sectional survey was conducted with 968 bereaved families of cancer patients in palliative care units across Japan. Five hundred thirty-seven responses were analyzed. (1) "Gratitude" was verbalized most often (families: 47%; patients: 61%), and "expressing forgiveness" least often (families: 16%; patients: 11%). (2) Even if the words were not used, 81.2% to 88.2% of families answered that they had received the patient's feelings, and 71.8% to 85.4% of families felt the patient had received their feelings. (3) Multiple logistic regression analyses indicated that the strongest attitudes determining verbalizing were "not wanting to say farewell without conveying feelings," "a daily basis of expressing," and "heart-to-heart communication" (ishin-denshin). For both families and patients, verbalizing feelings was difficult. Our results showed that families' and patients' verbalizing and receiving of feelings must be aligned to understand their communication at the end of life in Japan. Future research is needed to verify how attitude helps promote or inhibit verbalization. Copyright © 2017 John Wiley & Sons, Ltd.

Improving student achievement through daily activities and assessments in Introduction to Physics

NASA Astrophysics Data System (ADS)

Coppins, Kelly Ann

The combination of a hands-on approach to science with the accountability of daily assessments provides a greater opportunity for students who traditionally receive below-average grades to be successful in science classes. The addition of competitive elements and real world applications plays to their strengths as kinesthetic learners without sacrificing the rigor required to meet graduation standards. Further, daily assessment allows students to develop test-taking skills they will need for the standardized tests used by the state and for college admission. Finally, the combination of daily feedback and daily accountability prevents a struggling student from slipping through the cracks.

Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis.

PubMed

Ogura, Takashi; Taniguchi, Hiroyuki; Azuma, Arata; Inoue, Yoshikazu; Kondoh, Yasuhiro; Hasegawa, Yoshinori; Bando, Masashi; Abe, Shinji; Mochizuki, Yoshiro; Chida, Kingo; Klüglich, Matthias; Fujimoto, Tsuyoshi; Okazaki, Kotaro; Tadayasu, Yusuke; Sakamoto, Wataru; Sugiyama, Yukihiko

2015-05-01

A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone. Copyright ©ERS 2015.

United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results

PubMed Central

1988-01-01

From 1979 to 1985, 2435 patients thought to have had a transient ischaemic attack or minor ischaemic stroke were allocated at random to receive long term blind treatment with either aspirin 600 mg twice daily (n=815), aspirin 300 mg once daily (806), or placebo (814). Treatment continued with about 85% compliance until September 1986 (mean four years). The odds of suffering one or more of four categories of event—namely, non-fatal myocardial infarction, non-fatal major stroke, vascular death, or non-vascular death—were 18% less in the two groups allocated to receive aspirin than in the group allocated to receive placebo (2p=0·01). The more relevant but less frequent composite event of disabling stroke or vascular death was reduced by only 7%; this reduction was not significantly different from zero, but nor was it significantly different from a 25% reduction. There was no definite difference between responses to the 300 mg and 1200 mg daily doses, except that the lower dose was significantly less gastrotoxic. PMID:2894232

Post launch performance of the Meteor-3/TOMS instrument

NASA Technical Reports Server (NTRS)

Jaross, Glen; Ahmad, Zia; Cebula, Richard P.; Krueger, Arlin J.

1994-01-01

The Meteor-3/TOMS instrument is the second in a series of Total Ozone Mapping Spectrometers (TOMS) following the 1978 launch of Nimbus-7/TOMS. TOMS instruments are designed to measure total ozone amounts over the entire earth on a daily basis, and have been the cornerstone of ozone trend monitoring. Consequently, calibration is a critical issue, and is receiving much attention on both instruments. Performance and calibration data obtained by monitoring systems aboard the Meteor-3 instrument have been analyzed through the first full year of operation, and indicate that the instrument is performing quite well. A new system for monitoring instrument sensitivity employing multiple diffusers has been used successfully and is providing encouraging results. The 3-diffuser system has monitored changes in instrument sensitivity of a few percent despite decreases in diffuser reflectivity approaching 50 percent since launch.

Coffee and Caffeine Are Associated With Decreased Risk of Advanced Hepatic Fibrosis Among Patients With Hepatitis C.

PubMed

Khalaf, Natalia; White, Donna; Kanwal, Fasiha; Ramsey, David; Mittal, Sahil; Tavakoli-Tabasi, Shahriar; Kuzniarek, Jill; El-Serag, Hashem B

2015-08-01

Coffee or caffeine has been proposed to protect against hepatic fibrosis, but few data are available on their effects in patients with chronic hepatitis C virus (HCV) infection. We conducted a cross-sectional study of veterans with chronic HCV infection to evaluate the association between daily intake of caffeinated and decaffeinated coffee, tea, and soda, and level of hepatic fibrosis, based on the FibroSURE test (BioPredictive, Paris, France) (F0-F3, mild [controls] vs. F3/F4-F4, advanced). Models were adjusted for multiple potential confounders including age, alcohol abuse, and obesity. Among 910 patients with chronic HCV infection, 98% were male and 38% had advanced hepatic fibrosis. Daily intake of caffeinated coffee was higher among controls than patients with advanced fibrosis (1.37 vs. 1.05 cups/d; P = .038). In contrast, daily intake of caffeinated tea (0.61 vs. 0.56 cups/d; P = .651) or soda (1.14 vs. 0.95 cans/d; P = .106) did not differ between the groups. A higher percentage of controls (66.0%) than patients with advanced fibrosis (57.9%) consumed 100 mg or more of caffeine daily from all sources (P = .014); controls also received a larger proportion of their caffeine from coffee (50.2% vs. 43.0%; P = .035). Hepatoprotective effects of an average daily intake of 100 mg or more of caffeine (adjusted odds ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .020) and 1 cup or more of caffeinated tea by non-coffee drinkers (adjusted odds ratio, 0.56; 95% confidence interval, 0.34-0.94; P = .028) persisted after adjustment for confounders, including insulin resistance. A modest daily caffeine intake (as little as 100 mg) may protect against advanced hepatic fibrosis in men with chronic HCV infection. Additional research is needed to confirm these findings in women and in people with other chronic liver diseases. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Methicillin-resistant Staphylococcus aureus prolongs intensive care unit stay in ventilator-associated pneumonia, despite initially appropriate antibiotic therapy.

PubMed

Shorr, Andrew F; Combes, Alain; Kollef, Marin H; Chastre, Jean

2006-03-01

To determine the impact of methicillin-resistant Staphylococcus aureus (MRSA) on length of stay in the intensive care unit (ICU) for patients with ventilator-associated pneumonia (VAP) and to control for the effect of initially inappropriate antibiotic treatment on outcomes by focusing only on persons who were given appropriate antibiotic therapy for their infection. Retrospective analysis of pooled, patient-level data from multiple clinical trials in VAP. Multiple ICUs in France. Persons with bronchoscopically confirmed VAP due to either MRSA or methicillin-susceptible S. aureus (MSSA) and who received initially appropriate antibiotic treatment. All persons with MRSA VAP received vancomycin (15 mg/kg intravenously, twice daily). None. We compared patients with MRSA VAP to persons with MSSA VAP. ICU length of stay represented the primary end point and ICU-free days served as a secondary end point. We recorded information regarding multiple confounders, including demographics, reasons for ICU admission and mechanical ventilation (MV), severity of illness at both ICU admission and time of diagnosis of VAP, and duration of mechanical ventilation before and following the onset of VAP. The final cohort included 107 patients, and one third of cases were due to MRSA. Despite receiving initially appropriate antibiotic treatment, median ICU length of stay was significantly longer for persons with MRSA infection (33 days vs. 22 days; p=.047). The median number of ICU-free days was concomitantly lower in MRSA VAP (0 days vs. 5 days; p=.011). Survival analysis employing a Cox proportional hazards model identified several predictors of remaining in the ICU: Pao2/Fio2 ratio at diagnosis of VAP, duration of MV before VAP, duration of MV after diagnosis of VAP, and reason for MV. Additionally, infection with MRSA as opposed MSSA doubled the probability of needing continued ICU care (hazard ratio, 2.08; 95% confidence interval, 1.09-3.95; p=.025). MRSA VAP independently prolongs the duration of ICU hospitalization, and in turn, increases overall costs, even for patients initially given appropriate antibiotic treatment. Confronting the adverse impact of MRSA will require efforts that address more than the initial antibiotic prescription.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

PubMed

Xie, Jie; Cao, Jun; Wang, Jing-Fen; Zhang, Bai-Hong; Zeng, Xiao-Hua; Zheng, Hong; Zhang, Yang; Cai, Li; Wu, Yu-Dong; Yao, Qiang; Zhao, Xiao-Chun; Mao, Wei-Dong; Jiang, Ai-Mei; Chen, Shao-Shui; Yang, Shun-E; Wang, Shu-Sen; Wang, Jian-Hong; Pan, Yue-Yin; Ren, Bi-Yong; Chen, Yan-Ju; Ouyang, Li-Zhi; Lei, Kai-Jian; Gao, Jing-Hua; Huang, Wen-He; Huang, Zhan; Shou, Tao; He, Yan-Ling; Cheng, Jing; Sun, Yang; Li, Wei-Ming; Cui, Shu-de; Wang, Xin; Rao, Zhi-Guo; Ma, Hu; Liu, Wei; Wu, Xue-Yong; Shen, Wei-Xi; Cao, Fei-Lin; Xiao, Ze-Min; Wu, Biao; Tian, Shu-Yan; Meng, Dong; Shen, Peng; Wang, Bi-Yun; Wang, Zhonghua; Zhang, Jian; Wang, Leiping; Hu, Xi-Chun

2018-04-01

PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial.

PubMed

Gulati, Ashima; Sinha, Aditi; Sreenivas, Vishnubhatla; Math, Aparna; Hari, Pankaj; Bagga, Arvind

2011-01-01

Relapses of nephrotic syndrome often follow minor infections, commonly of the upper respiratory tract. Daily administration of maintenance prednisolone during intercurrent infections was examined to determine whether the treatment reduces relapse rates in children with frequently relapsing nephrotic syndrome. In a randomized controlled trial (nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic, frequently relapsing nephrotic syndrome eligible for therapy with prolonged low-dose, alternate-day prednisolone with or without levamisole were randomized to either receive their usual dose of alternate-day prednisolone daily for 7 days during intercurrent infections (intervention group) or continue alternate-day prednisolone (controls). Primary outcome was assessed by comparing the rates of infection-associated relapses at 12-month follow-up. Secondary outcomes were the frequency of infections and the cumulative amount of prednisolone received in both groups. Patients in the intervention group showed significantly lower infection-associated (rate difference, 0.7 episodes/patient per year; 95% confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9 episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity. Poisson regression, adjusted for occurrence of infections, showed that daily administration of prednisolone during infections independently resulted in 59% reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every six patients receiving this intervention, one showed a reduction of relapse frequency to less than three per year. Daily administration of maintenance doses of prednisolone, during intercurrent infections, significantly reduces relapse rates and the proportion of children with frequently relapsing nephrotic syndrome.

Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

PubMed Central

Barnewall, Roy E.; Comer, Jason E.; Miller, Brian D.; Gutting, Bradford W.; Wolfe, Daniel N.; Director-Myska, Alison E.; Nichols, Tonya L.; Taft, Sarah C.

2012-01-01

Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 102, 1 × 103, 1 × 104, and 1 × 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 102, 1 × 103, and 1 × 104 CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days. PMID:22919662

Evaluation of the efficacy of once-daily use of tadalafil vs. on-demand use. Is there a cumulative effect?

PubMed

Jamshidian, Hasan; Borhan, Armin; Kooraki, Soheil; Borhan, Arash

2012-11-01

To assess and compare the efficacy of on-demand versus daily dosages of tadalafil in the treatment of erectile dysfunction. The case-control double-blind study was conducted at the Department of Urology, Tehran University of Medical Science, Imam Khomeini Hospital, from March 2008 to January 2010. It comprised 100 males suffering from erectile dysfunction who were randomised into two groups; one receiving on-demand tadalafil (10mg), and the other receiving once-daily dose of tadalafil (10mg). The erectile function domain of the International Index of Erectile Function was evaluated initially at the baseline and then at 24 weeks after treatment. To evaluate the possible cumulative effect of tadalafil, the index was measured in the group taking daily tadalafil at 12 weeks after the initiation of the treatment. SPSS 13 was used for statistical analysis. The study showed significant improvement in the mean erectile function domain measured after 24 weeks in both daily (17.08+/-3.896 vs baseline 12.64+/-2.92; p<0.001) and on-demand (15.46+/-3.64 vs baseline 13.48+/-2.86; p<0.001) groups. Data showed significant difference in mean scores between on-demand and daily groups (p = 0.03). In daily group, the mean domain measured at the 24th week showed significant improvement compared to the mean score of the 12th week (p <0.001). Treatment with daily tadalafil was associated with a significantly higher erectile function domain score compared to the on-demand use. The significant difference between mean scores of 12th week and 24th week in the daily group points towards the possible cumulative effect of tadalafil.

Language Comprehension in Language-Learning Impaired Children Improved with Acoustically Modified Speech

NASA Astrophysics Data System (ADS)

Tallal, Paula; Miller, Steve L.; Bedi, Gail; Byma, Gary; Wang, Xiaoqin; Nagarajan, Srikantan S.; Schreiner, Christoph; Jenkins, William M.; Merzenich, Michael M.

1996-01-01

A speech processing algorithm was developed to create more salient versions of the rapidly changing elements in the acoustic waveform of speech that have been shown to be deficiently processed by language-learning impaired (LLI) children. LLI children received extensive daily training, over a 4-week period, with listening exercises in which all speech was translated into this synthetic form. They also received daily training with computer "games" designed to adaptively drive improvements in temporal processing thresholds. Significant improvements in speech discrimination and language comprehension abilities were demonstrated in two independent groups of LLI children.

Impact of continuous in-home rehabilitation on quality of life and activities of daily living in elderly clients over 1 year.

PubMed

Imanishi, Miyuki; Tomohisa, Hisao; Higaki, Kazuo

2017-11-01

To verify the effect of in-home rehabilitation on quality of life and activities of daily living in elderly clients. In this non-randomized controlled intervention trial, elderly participants were separated into a rehabilitation or a non-rehabilitation group (n = 100 each). The non-rehabilitation group received basic in-home nursing care, including assistance with cooking, cleaning, toileting, meals and medication. The rehabilitation group received a physical treatment program provided by a licensed professional once a week and basic nursing care in the home. For each group, quality of life and activities of daily living were assessed approximately every 3 months over a 1-year period. Quality of life was evaluated using the Philadelphia Geriatric Center Morale Scale, and activities of daily living were evaluated based on the Functional Independence Measure. The rehabilitation group showed statistically significant improvements in both quality of life and activities of daily living. In contrast, the non-rehabilitation group, although showing slight improvement in quality of life at 9 months, showed almost no effects at the other time-points and no significant changes in activities of daily living over the course of the study. The results of the present study suggest that long-term continuous in-home rehabilitation might improve quality of life and activities of daily living in elderly clients. Geriatr Gerontol Int 2017; 17: 1866-1872. © 2017 Japan Geriatrics Society.

Evaluation of the efficacy and safety of bromocriptine QR in type 2 diabetes.

PubMed

Ramteke, Karuna Balwant; Ramanand, Sunita Jaiprakash; Ramanand, Jaiprakash B; Jain, Suyog Subhas; Raparti, Girish Tulsidas; Patwardhan, Milind Hari; Murthy, Mangala; Ghanghas, Ravi G

2011-07-01

Diabetes mellitus is a chronic metabolic disorder of endocrinal origin with multiorgan involement. Today's physician has a lot many options to choose for treating type 2 diabetes, but does not always manages to achieve optimal glycemic control. The newer drug bromocriptine acts by novel hypothalamic circadian rhythm resetting mechanism. To evaluate the efficacy and safety of bromocriptine QR in type 2 diabetes. 105 patients according to inclusion and exclusion criteria were randomized into three groups by simple randomization. Group 1 received bromocriprine 2.4 mg once daily, group 2 received metformin 500 mg twice daily while group 3 received bromocriprine 1.6 mg daily and metformin 500 mg twice daily. Baseline measurement of fasting and postprandial blood sugar, HbA1(C) and BMI were followed up at 6(th) and 12(th) weeks. Safety evaluation was done by questioning the patient and also through routine hematological and biochemical parameters. Z test was used for analysis. Group 1 showed significant reduction in fasting and postprandial sugar and HbA(1c) at 12 weeks. While groups 2 and 3 showed even higher reduction in these parameters albeit with slightly more adverse drug events like nausea, vomiting compared to group 1. Bromocriptine QR is an effective and safe antidiabetic drug which can be employed as monotherapy or in conjuction with metformin to achieve and maintain optimal glycemic control.

A randomized trial to determine the optimal dosage of multivitamin supplements to reduce adverse pregnancy outcomes among HIV-infected women in Tanzania.

PubMed

Kawai, Kosuke; Kupka, Roland; Mugusi, Ferdinand; Aboud, Said; Okuma, James; Villamor, Eduardo; Spiegelman, Donna; Fawzi, Wafaie W

2010-02-01

We previously reported that supplementation with multivitamins (vitamin B complex, vitamin C, and vitamin E) at multiples of the Recommended Dietary Allowance (RDA) significantly decreased the risk of adverse pregnancy outcomes among HIV-infected women. The minimum dosage of multivitamins necessary for optimal benefits is unknown. We investigated the efficacy of multivitamin supplements at single compared with multiple RDAs on decreasing the risk of adverse pregnancy outcomes among HIV-infected women. We conducted a double-blind, randomized controlled trial among 1129 HIV-infected pregnant women in Tanzania. Eligible women between 12 and 27 gestational weeks were randomly assigned to receive daily oral supplements of either single or multiple RDA multivitamins from enrollment until 6 wk after delivery. Multivitamins at multiple and single doses of the RDA had similar effects on the risk of low birth weight (11.6% and 10.2%, respectively; P = 0.75). We found no difference between the 2 groups in the risk of preterm birth (19.3% and 18.4%, respectively; P = 0.73) or small-for-gestational-age (14.8% and 12.0%, respectively; P = 0.18). The mean birth weights were similar in the multiple RDA (3045 + or - 549 g) and single RDA multivitamins group (3052 + or - 534 g; P = 0.83). There were no significant differences between the 2 groups in the risk of fetal death (P = 0.99) or early infant death (P = 0.19). Multivitamin supplements at a single dose of the RDA may be as efficacious as multiple doses of the RDA in decreasing the risk of adverse pregnancy outcomes among HIV-infected women. This trial was registered at clinicaltrials.gov as NCT00197678.

A pharmacokinetic and pharmacodynamic comparison of immediate-release metoprolol and extended-release metoprolol CR/XL in patients with suspected acute myocardial infarction: a randomized, open-label study.

PubMed

Karlson, Björn W; Dellborg, Mikael; Gullestad, Lars; Aberg, Jan; Sugg, Jennifer; Herlitz, Johan

2014-01-01

Previous metoprolol studies in myocardial infarction patients were performed with immediate-release (IR) metoprolol. This study aims to evaluate if extended-release metoprolol CR/XL once daily gives a similar β-blockade over 24 h compared to multiple dosing of metoprolol IR. After 2 days of routine metoprolol treatment, 27 patients with suspected acute myocardial infarction were randomized to open-label treatment with metoprolol IR (50 mg four times daily or 100 mg twice daily) or metoprolol CR/XL 200 mg once daily for 3 days. Metoprolol CR/XL 200 mg once daily gave more pronounced suppression of peak heart rate, with lower peak and less variation in peak to trough plasma levels. There were no differences in AUC between the CR/XL and IR formulations, although the trough plasma metoprolol levels were comparable for metoprolol CR/XL 200 mg once daily and metoprolol IR 50 mg four times daily, but lower for metoprolol IR 100 mg twice daily. Both treatments were well tolerated. Metoprolol CR/XL 200 mg once daily showed lower peak and less variation in peak to trough plasma levels compared to multiple dosing of metoprolol IR with the same AUC. This was accompanied by a more uniform β-blockade over time, which was reflected by heart rate, and a more pronounced suppression of peak heart rate with similar tolerability. This suggests metoprolol CR/XL may be used as an alternative to metoprolol IR in patients with myocardial infarction. © 2013 S. Karger AG, Basel.

Relief of depression and pain improves daily functioning and quality of life in patients with major depressive disorder.

PubMed

Lin, Ching-Hua; Yen, Yung-Chieh; Chen, Ming-Chao; Chen, Cheng-Chung

2013-12-02

The objective of this study was to investigate the effects of depression relief and pain relief on the improvement in daily functioning and quality of life (QOL) for depressed patients receiving a 6-week treatment of fluoxetine. A total of 131 acutely ill inpatients with major depressive disorder (MDD) were enrolled to receive 20mg of fluoxetine daily for 6 weeks. Depression severity, pain severity, daily functioning, and health-related QOL were assessed at baseline and again at week 6. Depression severity, pain severity, and daily functioning were assessed using the 17-item Hamilton Depression Rating Scale, the Short-Form 36 (SF-36) Body Pain Index, and the Work and Social Adjustment Scale. Health-related QOL was assessed by three primary domains of the SF-36, including social functioning, vitality, and general health perceptions. Pearson's correlation and structural equation modeling were used to examine relationships among the study variables. Five models were proposed. In model 1, depression relief alone improved daily functioning and QOL. In model 2, pain relief alone improved daily functioning and QOL. In model 3, depression relief, mediated by pain relief, improved daily functioning and QOL. In model 4, pain relief, mediated by depression relief, improved daily functioning and QOL. In model 5, both depression relief and pain relief improved daily functioning and QOL. One hundred and six patients completed all the measures at baseline and at week 6. Model 5 was the most fitted structural equation model (χ(2) = 8.62, df = 8, p = 0.376, GFI = 0.975, AGFI = 0.935, TLI = 0.992, CFI = 0.996, RMSEA = 0.027). Interventions which relieve depression and pain improve daily functioning and QOL among patients with MDD. The proposed model can provide quantitative estimates of improvement in treating patients with MDD. © 2013 Elsevier Inc. All rights reserved.

Non-linear absorption pharmacokinetics of amoxicillin: consequences for dosing regimens and clinical breakpoints.

PubMed

de Velde, Femke; de Winter, Brenda C M; Koch, Birgit C P; van Gelder, Teun; Mouton, Johan W

2016-10-01

To describe the population pharmacokinetics of oral amoxicillin and to compare the PTA of current dosing regimens. Two groups, each with 14 healthy male volunteers, received oral amoxicillin/clavulanic acid tablets on two separate days 1 week apart. One group received 875/125 mg twice daily and 500/125 mg three times daily and the other group 500/125 mg twice daily and 250/125 mg three times daily. A total of 1428 amoxicillin blood samples were collected before and after administration. We analysed the concentration-time profiles using a non-compartmental pharmacokinetic method (PKSolver) and a population pharmacokinetic method (NONMEM). The PTA was computed using Monte Carlo simulations for several dosing regimens. AUC0-24 and Cmax increased non-linearly with dose. The final model included the following components: Savic's transit compartment model, Michaelis-Menten absorption, two distribution compartments and first-order elimination. The mean central volume of distribution was 27.7 L and mean clearance was 21.3 L/h. We included variability for the central volume of distribution (34.4%), clearance (25.8%), transit compartment model parameters and Michaelis-Menten absorption parameters. For 40% fT>MIC and >97.5% PTA, the breakpoints were 0.125 mg/L (500 mg twice daily), 0.25 mg/L (250 mg three times daily and 875 mg twice daily), 0.5 mg/L (500 mg three times daily) and 1 mg/L (750, 875 or 1000 mg three times daily and 500 mg four times daily). The amoxicillin absorption rate appears to be saturable. The PTAs of high-dose as well as twice-daily regimens are less favourable than regimens with lower doses and higher frequency. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial

PubMed Central

Kardas, Przemyslaw

2007-01-01

Background A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris. Methods One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life. Results The overall compliance was 86.5 ± 21.3% in the betaxolol group versus 76.1 ± 26.3% in the metoprolol group (p < 0.01), and the correct number of doses was taken on 84.4 ± 21.6% and 64.0 ± 31.7% of treatment days, respectively (p < 0.0001). The percentage of missed doses was 14.5 ± 21.5% in the once-daily group and 24.8 ± 26.4% in the twice-daily group (p < 0.01). The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01), correct interdose intervals (77.4% v 53.1%, p < 0.0001), and therapeutic coverage (85.6% vs 73.7%, p < 0.001) were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions. Conclusions The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris. PMID:17580734

Daily bowel care program

MedlinePlus

... a brain or spinal cord injury. People with multiple sclerosis also have problems with their bowels. Those with ... PA: Elsevier Saunders; 2016:chap 18. Read More Multiple sclerosis Recovering after stroke Patient Instructions Constipation - self-care ...

A randomized-controlled trial of intensive case management emphasizing the recovery model among patients with severe and enduring mental illness.

PubMed

O'Brien, S; McFarland, J; Kealy, B; Pullela, A; Saunders, J; Cullen, W; Meagher, D

2012-09-01

There is increasing interest in the application of recovery principles in mental health services. We studied the implementation of a programme of intensive case management (ICM) emphasizing recovery principles in a community mental health service in Ireland. Eighty service attenders with severe and enduring illness characterized by significant ongoing disability were randomized into (1) a group receiving a programme of ICM and (2) a group receiving treatment as usual (TAU). Groups were compared before and after the programme for general psychopathology using the Brief Psychiatric Rating Scale (BPRS) (clinician rated) and How are You? scale (self-rated). The Functional Analysis of Care Environments (FACE) scale provided assessment of multiple functional domains. The overall group (mean age 44.5 ± 13.2 years; 60% male) had mean total Health of the Nation Outcome Scale (HoNOS) scale scores of 10.5 ± 4.6, with problems in social functioning especially prominent (mean social subscale score 5.0 ± 2.7). The ICM group were younger (p < 0.01) with higher baseline scores on the HoNOS social subscale and BPRS (p < 0.05). An analysis of covariance, controlling for these baseline differences, indicated greater improvement in BPRS scores (p = 0.001), How are You? scores (p = 0.02) and FACE domains for cognition, symptoms and interpersonal relationships (all p < 0.001) in the ICM group. The ICM group underwent greater changes in structured daily activities that were linked to improved BPRS scores (p = 0.01). A programme of ICM emphasizing recovery principles resulted in significant improvement across psychopathological and functional domains. Improvements were linked to enhanced engagement with structured daily activities. Recovery-oriented practices can be integrated into existing mental health services and provided alongside traditional models of care.

Differences in self-monitored, blood glucose test strip utilization by therapy for type 2 diabetes mellitus.

PubMed

Tavares, Ruben; Duclos, Marc; Brabant, Marie-Josée; Checchin, Daniella; Bosnic, Nevzeta; Turvey, Katherine; Terres, Jorge Alfonso Ross

2016-06-01

To determine whether blood glucose test strip (BGTS) utilization in patients with type 2 diabetes (T2D) is associated with the type of diabetes therapy, classified according to hypoglycemic risk. A retrospective, longitudinal (2006-2012) study of Canadian private drug plans (PDP) and Ontario Public Drug Programs (OPDP) prescription claims was conducted. Analyses were restricted to patients with T2D with or without a claim for BGTS. Daily BGTS utilization (TS/patient/day) was evaluated by diabetes therapy classified by hypoglycemic risk. Multivariate analyses were conducted to identify determinants of BGTS utilization. The T2D cohort comprised 5,759,591 observations from 1,949,129 claimants. Mean BGTS utilization was 0.84 TS/patient/day and differed between PDP and OPDP (0.66 vs. 1.00). Daily utilization was greatest in patients receiving therapy associated with a pre-defined high risk of hypoglycemia [insulin: basal + bolus (2.16), premixed (1.65), basal (1.16), other insulin regimens (2.13), and sulfonylureas (0.74)] versus non-sulfonylurea non-insulin-based regimens (0.52). For non-insulin therapy, BGTS utilization was greater for patients on multiple non-insulin therapies versus monotherapy (0.74 vs. 0.53 TS/patient/day). In multivariate analyses, drivers for BGTS utilization included insulin use, previous BGTS use, and female gender. Previous diabetes therapy and duration of therapy were negatively correlated with BGTS utilization. BGTS utilization varies depending on the type of therapy used to treat T2D according to hypoglycemic risk. Decision making regarding BGTS needs to account for robust analyses of current utilization and its value in those settings, including in patients not receiving diabetes therapy and the prevalence of circumstances conducive to more intensive monitoring.

Role of treatment for depressive symptoms in relieving the impact of fatigue in HIV-HCV co-infected patients: ANRS Co13 Hepavih, France, 2006-2008.

PubMed

Michel, L; Villes, V; Dabis, F; Spire, B; Winnock, M; Loko, M-A; Poizot-Martin, I; Valantin, M A; Bonnard, P; Salmon-Céron, D; Carrieri, M P

2010-09-01

Fatigue is a major component of quality of life (QOL) and is associated with depression in HIV-HCV co-infected individuals. We investigated whether treating depressive symptoms (DS) could mitigate the impact of fatigue on daily functioning in co-infected patients, even those at an advanced stage of disease. The analysis was conducted on enrollment data of 328 HIV-HCV co-infected patients recruited in the French nationwide ANRS CO 13 HEPAVIH cohort. Data collection was based on medical records and self-administered questionnaires which included items on socio-behavioural data, the fatigue impact scale (FIS) in three domains (cognitive, physical and social functioning), depressive symptoms (CES-D classification) and use of treatments for depressive symptoms (TDS). After multiple adjustment for gender and unemployment, CD4 cell count <200 per mm(3) was associated with a negative impact of fatigue on the physical functioning dimension (P = 0.002). A higher number of symptoms causing discomfort significantly predicted a higher impact of fatigue on all three dimensions (P < 0.001). This was also true for patients with DS receiving TDS when compared with those with no DS but receiving TDS. A significant decreasing linear trend (P < 0.001) of the impact of fatigue was found across the categories 'DS/TDS', 'DS/no TDS', 'no DS/TDS' and 'no DS/no TDS'. Despite limitations related to the cross-sectional nature of this study, our results suggest that routine screening and treatment for DS can reduce the impact of fatigue on the daily functioning of HIV-HCV co-infected patients and relieve the burden of their dual infection.

Protective effect of artichoke (Cynara scolymus) leaf extract against lead toxicity in rat.

PubMed

Heidarian, Esfandiar; Rafieian-Kopaei, Mahmoud

2013-09-01

Artichoke, Cynara scolymus L. (Asteraceae), has many natural antioxidants and multiple pharmacological actions. Recent studies have shown that it has antitoxic activity. Lead (Pb) is a dangerous environmental toxicant that induces a broad range of dysfunctions in human. This study evaluated the protective effect of the hydroethanolic extract of artichoke against altered biochemical parameters in rats fed with lead-containing diet. Thirty-two rats were randomly divided into four groups. The first (control) group received standard diet. The second, third and fourth groups received 500 mg lead/kg diet, 500 mg lead/kg diet plus 300 mg/kg b.w. artichoke extract daily, and 500 mg lead/kg diet plus 1 mg vitamin C/100 g b.w. daily for 6 weeks, respectively. Serum lead, lipoprotein profile, ALT (alanine transaminase), AST (aspartate transaminase), ALP (alkaline phosphatase), malondialdehyde (MDA) and liver histopathology assessments were conducted. Serum lead, triglyceride (TG), VLDL, ALT, AST, ALP and MDA levels decreased significantly (p < 0.05) in the artichoke-treated group (35.85, 38.26, 38.38, 21.90, 12.81, 26.86 and 46.91%, respectively) compared to lead-intoxicated rats without treatment. No significant change was observed in serum lead, ALP and ALT between artichoke and vitamin C-treated groups (p > 0.05). Furthermore, the liver histopathology in rats treated with artichoke showed a mild degree of lymphocyte infiltration that was relatively comparable to the control and vitamin C-treated groups. These results clearly show that the artichoke extract in lead-poisoned rats has suitable chelating properties for the reduction of blood lead levels.

Practice and documentation of palliative sedation: a quality improvement initiative

PubMed Central

McKinnon, M.; Azevedo, C.; Bush, S.H.; Lawlor, P.; Pereira, J.

2014-01-01

Background Palliative sedation (ps), the continuous use of sedating doses of medication to intentionally reduce consciousness and relieve refractory symptoms at end of life, is ethically acceptable if administered according to standards of best practice. Procedural guidelines outlining the appropriate use of ps and the need for rigorous documentation have been developed. As a quality improvement strategy, we audited the practice and documentation of ps on our palliative care unit (pcu). Methods A pharmacy database search of admissions in 2008 identified, for a subsequent chart review, patients who had received either a continuous infusion of midazolam (≥10 mg/24 h), regular parenteral dosing of methotrimeprazine (≥75 mg daily), or regular phenobarbital. Documentation of the decision-making process, consent, and medication use was collected using a data extraction form based on current international ps standards. Results Interpretation and comparison of data were difficult because of an apparent lack of a consistent operational definition of ps. Patient records had no specific documentation in relation to ps initiation, to clearly identified refractory symptoms, and to informed consent in 60 (64.5%), 43 (46.2%), and 38 (40.9%) charts respectively. Variation in the medications used was marked: 54 patients (58%) were started on a single agent and 39 (42%), on multiple agents. The 40 patients (43%) started on midazolam alone received a mean daily dose of 21.4 mg (standard deviation: 24.6 mg). Conclusions The lack of documentation and standardized practice of ps on our pcu has resulted in a quality improvement program to address those gaps. They also highlight the importance of conducting research and developing clinical guidelines in this area. PMID:24764700

Ethical conflict in nurse practitioners and physician assistants in managed care.

PubMed

Ulrich, Connie M; Danis, Marion; Ratcliffe, Sarah J; Garrett-Mayer, Elizabeth; Koziol, Deloris; Soeken, Karen L; Grady, Christine

2006-01-01

More patients are receiving healthcare services from nurse practitioners (NPs) and physician assistants (PAs). These providers are likely to be confronted with a variety of ethical issues as they balance quality care with their patients' rising cost concerns. However, very little is known about the ethical conflicts and causes of these conflicts experienced by these clinicians in their daily practice. To identify ethical concerns and conflicts NPs and PAs encounter related to managed care in the delivery of primary care to patients and the factors that influence ethical conflict. A cross-sectional self-administered mailed questionnaire was sent to 3,900 NPs and PAs randomly selected from primary care and primary care subspecialties in the United States (adjusted response rate, 50.6%). Respondents were surveyed on ethical issues and concerns, ethics preparedness, and ethical conflict. Bivariate and multiple linear regression analyses were used to evaluate predictors of ethical conflict. Insurance constraints were reported to have interfered with the ability to provide quality patient care by 72% of respondents, with 55.3% reporting daily to weekly interferences. Nearly half of respondents (47%) have been asked by a patient to mislead insurers to assist them in receiving care. A perceived obligation to advocate for patients, even if it means exaggerating the severity of a patient's condition, was the single most significant predictor of ethical conflict, explaining 25% of the variance. NPs and PAs are experiencing ethical conflict often associated with their perceived professional obligations to advocate for patients. Being well-prepared in ethics and having sufficient professional independence help clinicians balance the ethical complexities and demands of meeting patients' needs within a constrained healthcare system.

Impact of an EMR-Based Daily Patient Update Letter on Communication and Parent Engagement in a Neonatal Intensive Care Unit

PubMed Central

Palma, Jonathan P.; Keller, Heather; Godin, Margie; Wayman, Karen; Cohen, Ronald S.; Rhine, William D.; Longhurst, Christopher A.

2013-01-01

Summary Objective To evaluate the impact of using electronic medical record (EMR) data in the form of a daily patient update letter on communication and parent engagement in a level II neonatal intensive care unit (NICU). Study Design Parents of babies in a level II NICU were surveyed before and after the introduction of an EMR-generated daily patient update letter, Your Baby’s Daily Update (YBDU). Results Following the introduction of the EMR-generated daily patient update letter, 89% of families reported using YBDU as an information source; 83% of these families found it “very useful”, and 96% of them responded that they “always” liked receiving it. Rates of receiving information from the attending physician were not statistically significantly different pre- and post-implementation, 81% and 78%, respectively (p = 1). Though there was no statistically significant improvement in parents’ knowledge of individual items regarding the care of their babies, a trend towards statistical significance existed for several items (p <.1), and parents reported feeling more competent to manage information related to the health status of their babies (p =.039). Conclusion Implementation of an EMR-generated daily patient update letter is feasible, resulted in a trend towards improved communication, and improved at least one aspect of parent engagement—perceived competence to manage information in the NICU. PMID:23730532

Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment.

PubMed

Saag, Kenneth G; Whelton, Andrew; Becker, Michael A; MacDonald, Patricia; Hunt, Barbara; Gunawardhana, Lhanoo

2016-08-01

Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ). Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function. © 2016, American College of Rheumatology.

Efficacy of twice-daily vs once-daily sessions of repetitive transcranial magnetic stimulation in the treatment of major depressive disorder: a retrospective study

PubMed Central

Modirrousta, Mandana; Meek, Benjamin P; Wikstrom, Sara L

2018-01-01

Purpose There is no clinical consensus on the optimal protocol for the treatment of major depressive disorder (MDD) using repetitive transcranial magnetic stimulation (rTMS). Accelerated protocols using more than a single session of treatment per day have been suggested as a means to reduce the overall length of time required for rTMS therapy. The objective of this study is to compare the treatment outcomes of patients with MDD who received two sessions of rTMS per day vs those who received one session per day, keeping the overall number of delivered pulses constant. Patients and methods In a retrospective study, we compared treatment outcomes of 36 patients with MDD who received 30 sessions of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. Patients received 3,000 pulses per session (5 s trains, 25 s intertrain interval) at 110% of resting motor threshold using a figure-eight coil. Patients received either two rTMS sessions per day (n=17) or one session per day (n=19). Depression symptoms were assessed by a psychiatrist using the Hamilton Rating Scale for Depression at baseline and after every 10 sessions of rTMS. Results The majority of patients in both groups responded to treatment, and there was a trend toward greater response rate in the twice-daily (TD) group (82.4%) compared to the once-daily (OD) group (52.6%). TD stimulation was tolerable for patients and produced no adverse side effects. Patients in the TD group experienced an improvement in symptoms faster than the OD group due to the accelerated therapy period. Conclusion Administration of two rTMS treatment sessions per day is tolerable for patients and does not seem to be inferior in efficacy to a OD protocol. TD administration has the benefit of producing symptom improvement over a shorter time span and requires fewer visits to the clinic. PMID:29398915

Frequency Hopping, Multiple Frequency-Shift Keying, Coding, and Optimal Partial-Band Jamming.

DTIC Science & Technology

1982-08-01

receivers appropriate for these two strategies. Each receiver is noncoherent (a coherent receiver is generally impractical) and implements hard...Advances in Coding and Modulation for Noncoherent Channels Affected by Fading, Partial Band, and Multiple- . Access Interference, in A. J. Viterbi...Modulation for Noncoherent Channels Affected by Fading, Partial Band, and Multiple-Access interference, in A. J. Viterbi, ed., Advances in Coumunication

Overdose and prescribed opioids: Associations among chronic non-cancer pain patients

PubMed Central

Dunn, Kate M; Saunders, Kathleen W; Rutter, Carolyn M; Banta-Green, Caleb J; Merrill, Joseph O; Sullivan, Mark D; Weisner, Constance M; Silverberg, Michael J; Campbell, Cynthia I; Psaty, Bruce M; Von Korff, Michael

2010-01-01

Background Chronic opioid therapy for chronic non-cancer pain (CNCP) is increasingly common in community practice. Concomitant with this practice change, rates of fatal opioid overdose have increased. It is not known to what extent overdose risks are elevated among patients receiving medically prescribed chronic opioid therapy. Objective To estimate rates of opioid overdose and their association with average prescribed daily opioid dose among patients receiving medically prescribed chronic opioid therapy. Design Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at time of overdose. Setting Health maintenance organization. Patients Individuals (n=9940) who received 3+ opioid prescriptions within 90-days for CNCP between 1997 and 2005. Measurements Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes, non-fatal and fatal overdoses, were identified through diagnostic codes from inpatient and outpatient care and death certificates and confirmed by medical record review. Results Fifty-one opioid-related overdoses were identified, including six deaths. Compared to patients receiving 1-20mg of opioids per day (0.2% annual overdose rate), patients receiving 50-99 mg had a 3.7 fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7% annual overdose rate. Patients receiving 100mg or more per day had an 8.9 fold increase in overdose risk (95% C.I. 4.0, 19.7) and a 1.8% annual overdose rate. Limitations Increased overdose risk among patients on higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation. Conclusions Patients receiving higher doses of prescribed opioids are at increased risk of opioid overdose, underscoring the need for close supervision of these patients. PMID:20083827

Energy expenditure estimation during daily military routine with body-fixed sensors.

PubMed

Wyss, Thomas; Mäder, Urs

2011-05-01

The purpose of this study was to develop and validate an algorithm for estimating energy expenditure during the daily military routine on the basis of data collected using body-fixed sensors. First, 8 volunteers completed isolated physical activities according to an established protocol, and the resulting data were used to develop activity-class-specific multiple linear regressions for physical activity energy expenditure on the basis of hip acceleration, heart rate, and body mass as independent variables. Second, the validity of these linear regressions was tested during the daily military routine using indirect calorimetry (n = 12). Volunteers' mean estimated energy expenditure did not significantly differ from the energy expenditure measured with indirect calorimetry (p = 0.898, 95% confidence interval = -1.97 to 1.75 kJ/min). We conclude that the developed activity-class-specific multiple linear regressions applied to the acceleration and heart rate data allow estimation of energy expenditure in 1-minute intervals during daily military routine, with accuracy equal to indirect calorimetry.

Life after the game--injury profile of past elite Australian football players.

PubMed

King, Tyler; Rosenberg, Michael; Braham, Rebecca; Ferguson, Renee; Dawson, Brian

2013-07-01

To investigate the long-term health and well-being of past elite Australian Football League (AFL) players, with particular emphasis on the effect of playing injuries on current lifestyle. Cross sectional survey. A health and well-being survey, completed by past AFL players (n=592) with mean (±SD) age of 55.1 y (±15.8) and playing career of 7.7 y (±4.1) sought information on demographics, education and employment, subjective well-being, lifestyle behaviours, physical health, disease prevalence, community and social structures, and playing history. A majority of past players experienced serious injuries (76%) and concussion (73%) throughout their career, both increasing significantly with the number of games played. Of those who received injuries, 60% require on-going treatment, yet only 6% receive treatment costs covered by their club or the AFL Players' Association. A large proportion (64%) of respondents are affected in daily life from previous AFL injuries. AFL careers are compounded by high injury rates, including loss of consciousness with a high incidence of multiple concussions amongst those players reporting a serious injury. Greater number of injuries received will further the likelihood of requiring on-going treatment and being affected later in life. Additional research and planning may be important in assisting other improvements in the quality of life of past AFL players. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Food and Nutrient Intake among 12-Month-Old Norwegian-Somali and Norwegian-Iraqi Infants.

PubMed

Grewal, Navnit Kaur; Andersen, Lene Frost; Kolve, Cathrine Solheim; Kverndalen, Ingrid; Torheim, Liv Elin

2016-09-28

The aim of the present paper was to describe food and nutrient intake among 12-month-old Norwegian-Somali and Norwegian-Iraqi infants, with a focus on iron and vitamin D intake. A cross-sectional survey was conducted from August 2013 through September 2014. Eighty-nine mothers/infants of Somali origin and 77 mothers/infants of Iraqi origin residing in Eastern Norway participated in the study. Data were collected using two 24-h multiple-pass recalls. Forty percent of the Norwegian-Somali infants and 47% of the Norwegian-Iraqi infants were breastfed at 12 months of age ( p = 0.414). Median energy percentages (E%) from protein, fat and carbohydrates were within the recommended intake ranges, except the level of saturated fats (12-13 E%). Median intakes of almost all micronutrients were above the recommended daily intakes. Most of the infants consumed iron-enriched products (81%) and received vitamin D supplements (84%). The median intakes of iron and vitamin D were significantly higher among infants receiving iron-enriched products and vitamin D supplements compared to infants not receiving such products ( p < 0.001). The findings indicate that the food and nutrient intake of this group of infants in general seems to be in accordance with Norwegian dietary recommendations. Foods rich in iron and vitamin D supplements were important sources of the infants' intake of iron and vitamin D and should continue to be promoted.

Event and Cost Offsets of Switching 20% of the Type 1 Diabetes Population in Germany From Multiple Daily Injections to Continuous Subcutaneous Insulin Infusion: A 4-Year Simulation Model.

PubMed

Zöllner, York Francis; Ziegler, Ralph; Stüve, Magnus; Krumreich, Julia; Schauf, Marion

2016-09-01

Most patients with type 1 diabetes (T1D) administer insulin by multiple daily injections (MDI). However, continuous subcutaneous insulin infusion (CSII) therapy has been shown to improve glycemic control compared with MDI. The objective was to determine the key medical event and cost offsets generated over a 4-year period by introducing CSII to T1D patients who have inadequately controlled glucose metabolism on MDI in Germany. A decision-analytic budget impact model, simulating a treatment switch scenario, was developed. In the base case, all T1D patients received MDI, while in the switch scenario, 20% of the eligible T1D population, randomly selected, moved to CSII. The model focused on 2 medical endpoints and their corresponding cost offsets: severe hypoglycemic events requiring hospitalization (SHEH) and complication-borne diabetic events (CDEs) avoided. Event rates and costs were taken from the literature and official sources, adopting a health insurance perspective. Compared with the base case, treating 20% of patients with CSII in the switch scenario resulted in 47 864 fewer SHEH and 5543 fewer CDEs. This led to total cost offsets of €183 085 281 within the 4-year time horizon. Of these, 92% were driven by avoided SHEH. Compared to an expected budget impact (cost increase) of 83%, only treatment costs considered, the total impact of the switch scenario amounted merely to a 24.5% increase in costs (reduction by 58.5% points; a factor of 3.4). The use of CSII resulted in fewer SHEH and CDEs compared to MDI. The incurred CSII implementation costs are hence offset to a substantial degree by cost savings in complication treatment. © 2016 Diabetes Technology Society.

Pharmacodynamics and pharmacokinetics of single doses of subcutaneous pegylated human G-CSF mutant (Ro 25-8315) in healthy volunteers: comparison with single and multiple daily doses of filgrastim.

PubMed

van Der Auwera, P; Platzer, E; Xu, Z X; Schulz, R; Feugeas, O; Capdeville, R; Edwards, D J

2001-04-01

Ro 25-8315 is produced by conjugation of rhG-CSF mutant with polyethylene glycol (PEG). The purpose of this study was to examine the pharmacodynamics and pharmacokinetics of Ro 25-8315 in comparison with Filgrastim (rhG-CSF). Subjects received single subcutaneous doses of Ro 25-8315 ranging from 10 to 150 microg/kg using a double-blind, randomized, placebo-controlled design. Filgrastim was administered as a single dose (5 or 10 microg/kg) and, following a 14-day washout period, daily for 7 days. Ro 25-8315 increased absolute neutrophil count (ANC) by 6- to 8-fold and CD34+ cell count more than 30-fold at the highest doses tested. Single doses (60-150 microg/kg) of Ro 25-8315 and multiple doses of Filgrastim had similar effects on ANC and CD34+, although Ro 25-8315 had a greater effect on CFU-GM. The pharmacokinetics of Ro 25-8315 were dose-dependent, with peak concentrations and area under the serum concentration-time curve (AUC) increasing 100-fold over the range of doses studied. Time to reach peak concentration (T(max)) and half-life of Ro 25-8315 averaged 20-30 hr at all doses, approximately three times longer than with Filgrastim. Adverse events were not serious and occurred with similar frequency with both products. Pegylation of rhG-CSF mutant results in more desirable pharmacokinetic properties and a longer duration of action with effective increases in ANC and measures of peripheral blood progenitor cell mobilization for at least 1 week. Copyright 2001 Wiley-Liss, Inc.

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women
.

PubMed

Schultze-Mosgau, Marcus-Hillert; Schuett, Barbara; Hafner, Frank-Thorsten; Zollmann, Frank; Kaiser, Andreas; Hoechel, Joachim; Rohde, Beate

2017-01-01

Vilaprisan is a novel, potent, and highly selective progesterone receptor modulator, which might offer a promising option for the treatment of uterine fibroids. In this randomized, placebo-controlled, parallel-group phase 1 study, the pharmacokinetics and safety of vilaprisan were investigated in healthy postmenopausal women. Subjects received a single oral dose of vilaprisan (1, 5, 15, or 30 mg) or placebo and - after a wash-out period - daily doses of the same strength over 28 days. Safety assessments included vital signs, ECGs, clinical laboratory tests, and adverse events. Blood samples for pharmacokinetic (PK) profiles were collected over 14 days after single dose (sd) and multiple dose (md; day 28). Vilaprisan was well tolerated. Mild to moderate adverse events occurred with similar frequency at all dose levels. Following single dose, maximum vilaprisan concentrations were observed 1 - 2 hours post-dose. Terminal half-lives ranged from 31 to 38 hours. Maximum concentrations of vilaprisan (Cmax) and exposure to vilaprisan (AUC) increased roughly dose-proportionally from 3.74 µg/L (1 mg) to 68.6 µg/L (30 mg) and 58.5 µg×h/L to 1,590 µg×h/L, respectively. With daily dosing, accumulation consistent with the long terminal half-life was observed (AUC(0-24)md/AUC(0-24)sd ratios: 1.9 to 3.2). The ratio AUC(0-24)md/AUCsd increased with dose from ~ 1 (1 mg) to 1.5 (30 mg). Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range.
.

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

PubMed Central

Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

2015-01-01

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study.

PubMed

Huang, Fenglei; Marzin, Kristell; Koenen, Rüdiger; Kammerer, Klaus Peter; Strelkowa, Natalja; Elgadi, Mabrouk; Quinson, Anne-Marie; Haertter, Sebastian

2017-10-01

Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by 240 mg faldaprevir once daily from day 6 to day 10, with an additional single dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples for the statins were collected on days 1-3 and days 10-12. Concomitant administration with faldaprevir led to approximately 9-fold and 34-fold increases in AUC 0-∞ and C max , respectively, of atorvastatin and approximately 15-fold and 33-fold increases in AUC 0-∞ and C max , respectively, of rosuvastatin, compared with the statins given alone. Exposure to the major metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased to a similar magnitude as that of the parent compounds. The marked drug-drug interaction observed is most likely related to the inhibitory effects of faldaprevir on transporters, particularly hepatic uptake transporters such as OTAP1B1 and OATP1B3. Given the significant increase in exposure to statins in healthy volunteers, coadministration of faldaprevir with statins should be avoided. © 2017, The American College of Clinical Pharmacology.

Longitudinal Changes in Disabled Husbands' and Wives' Receipt of Care

ERIC Educational Resources Information Center

Noel-Miller, Claire

2010-01-01

Purpose of the Study: This study contrasts 2-year adjustments in disabled husbands' and wives' amount of received care following both worsening and recovery in personal (activities of daily living [ADLs]) and routine care (instrumental activities of daily living [IADLs]) disability. Design and Methods: Using longitudinal data on 789 husbands and…

Water quality ramifications of manure storage and daily haul during winter and early spring

USDA-ARS?s Scientific Manuscript database

Manure storage is supported by the United States Natural Resources Conservation Service (NRCS) as a nutrient management strategy for controlling air and water quality. Daily haul is still a popular practice on the small farms in northeastern USA but receives criticism over the impact of spreading du...

Phase I study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with 5-fluorouracil and leucovorin: a safe combination.

PubMed

Hoekstra, R; de Vos, F Y F L; Eskens, F A L M; de Vries, E G E; Uges, D R A; Knight, R; Carr, R A; Humerickhouse, R; Verweij, J; Gietema, J A

2006-03-01

We performed a phase I study with the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 combined with 5-fluorouracil and leucovorin (5-FU/LV) to determine safety profile and assess pharmacokinetic interactions. Patients with advanced solid malignancies received LV 20 mg/m(2) followed by 5-FU 425 mg/m(2) both administered intravenously in 15 min daily for 5 days every 4 weeks. ABT-510 was administered subcutaneously twice daily continuously from day 2 onwards. Blood and urine samples for pharmacokinetic analyses were collected at days 1, 5 and 22. Twelve patients received a total of 45 cycles of 5-FU/LV combined with ABT-510. ABT-510 dose levels studied were 50 and 100 mg. The combination was well tolerated, with a toxicity profile comparable to that of 5-FU/LV alone. At the dose levels studied no significant pharmacokinetic interactions were observed. These data indicate that ABT-510 administered twice daily subcutaneously can be safely combined with 5-FU/LV administered daily for 5 days, every 4 weeks.

Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

NASA Technical Reports Server (NTRS)

Fiorindo, R. P.; Negulesco, J. A.

1980-01-01

Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

Is There Extra Cost of Institutional Care for MS Patients?

PubMed Central

Noyes, Katia; Bajorska, Alina; Weinstock-Guttman, Bianca

2013-01-01

Throughout life, patients with multiple sclerosis (MS) require increasing levels of support, rehabilitative services, and eventual skilled nursing facility (SNF) care. There are concerns that access to SNF care for MS patients is limited because of perceived higher costs of their care. This study compares costs of caring for an MS patient versus those of a typical SNF patient. We merged SNF cost report data with the 2001–2006 Nursing Home Minimum Data Set (MDS) to calculate percentage of MS residents-days and facility case-mix indices (CMIs). We estimated the average facility daily cost using hybrid cost functions, adjusted for facility ownership, average facility wages, CMI-adjusted number of SNF days, and percentage of MS residents-days. We describe specific characteristics of SNF with high and low MS volumes and examine any sources of variation in cost. MS patients were no longer more costly than typical SNF patients. A greater proportion of MS patients had no significant effect on facility daily costs (P = 0.26). MS patients were more likely to receive care in government-owned facilities (OR = 1.904) located in the Western (OR = 2.133) and Midwestern (OR = 1.3) parts of the USA (P < 0.05). Cost of SNF care is not a likely explanation for the perceived access barriers that MS patients face. PMID:24163769

Daily feeding of diclazuril top dress pellets in foals reduces seroconversion to Sarcocystis neurona.

PubMed

Pusterla, Nicola; Packham, Andrea; Mackie, Sarah; Kass, Philip H; Hunyadi, Laszlo; Conrad, Patricia A

2015-11-01

Thirty-three foals from a farm with a high exposure rate to Sarcocystis neurona were assigned to either an untreated or a diclazuril-treated group. Treated foals received daily 0.5 mg/kg of diclazuril pellets from 1 to 12 months of age. Monthly blood was tested for IgG against S. neurona using the indirect fluorescent antibody test. Following ingestion of colostral antibodies to S. neurona, there was a steady and continuous decline in seroprevalence to S. neurona until foals from both groups reached weaning age. Thereafter, the untreated foal group showed a significant increase in monthly seroprevalence compared to the diclazuril-treated foal group. The difference in temporal seroprevalence could be explained by the successful reduction of S. neurona infection in foals receiving a daily low-dose diclazuril. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measurement of solar radiation at the Earth's surface

NASA Technical Reports Server (NTRS)

Bartman, F. L.

1982-01-01

The characteristics of solar energy arriving at the surface of the Earth are defined and the history of solar measurements in the United States presented. Radiation and meteorological measurements being made at solar energy meteorological research and training sites and calibration procedures used there are outlined. Data illustrating the annual variation in daily solar radiation at Ann Arbor, Michigan and the diurnal variation in radiation at Albuquerque, New Mexico are presented. Direct normal solar radiation received at Albuquerque is contrasted with that received at Maynard, Massachusetts. Average measured global radiation for a period of one year for four locations under clear skies, 50% cloud cover, and 100% cloud cover is given and compared with the solar radiation at the top of the atmosphere. The May distribution of mean daily direct solar radiation and mean daily global solar radiation over the United States is presented. The effects of turbidity on the direct and circumsolar radiation are shown.

Predicting daily use of urban forest recreation sites

Treesearch

John F. Dwyer

1988-01-01

A multiple linear regression model explains 90% of the variance in daily use of an urban recreation site. Explanatory variables include season, day of the week, and weather. The results offer guides for recreation site planning and management as well as suggestions for improving the model.

Motivational interviewing for improving recovery after stroke.

PubMed

Cheng, Daobin; Qu, Zhanli; Huang, Jianyi; Xiao, Yousheng; Luo, Hongye; Wang, Jin

2015-06-03

Psychological problems are common complications following stroke that can cause stroke survivors to lack the motivation to take part in activities of daily living. Motivational interviewing provides a specific way for enhancing intrinsic motivation, which may help to improve activities of daily living for stroke survivors. To investigate the effect of motivational interviewing for improving activities of daily living after stroke. We searched the Cochrane Stroke Group's Trials Register (November 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1), MEDLINE (1948 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), PsycINFO (1806 to March 2015), PsycBITE (March 2015) and four Chinese databases. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers and conference proceedings, checked reference lists, and contacted authors of relevant studies. Randomised controlled trials (RCTs) comparing motivational interviewing with no intervention, sham motivational interviewing or other psychological therapy for people with stroke were eligible. Two review authors independently selected studies for inclusion, extracted eligible data and assessed risk of bias. Outcome measures included activities of daily living, mood and death. One study involving a total of 411 participants, which compared motivational interviewing with usual care, met our inclusion criteria. The results of this review did not show significant differences between groups receiving motivational interviewing or usual stroke care for participants who were not dependent on others for activities of daily living, nor on the death rate after three-month and 12-month follow-up, but participants receiving motivational interviewing were more likely to have a normal mood than those who received usual care at three-months and 12-months follow-up. There is insufficient evidence to support the use of motivational interviewing for improving activities of daily living after stroke. Further well designed RCTs are needed.

Intervention study shows suboptimal growth among children receiving a food supplement for five months in a slum in Bangladesh

PubMed Central

Choudhury, Nuzhat; Bromage, Sabri; Alam, M. Ashraful; Ahmed, A.M. Shamsir; Islam, M. Munirul; Hossain, M. Iqbal; Mahfuz, Mustafa; Mondal, Dinesh; Haque, M. Rashidul; Ahmed, Tahmeed

2017-01-01

Aim This study assessed weight and height changes among underweight children who received a locally produced, cereal-based, ready-to-use supplementary food. Methods We recruited 500 underweight Bangladeshi children aged 6–23 months from a Dhaka slum and individually matched them by sex and neighbourhood with 480 well-nourished controls. The intervention group received the daily food supplement for five months and both groups received daily micronutrient supplements. Their weight, height, mid-upper-arm circumference and head circumference were measured monthly. Results The children’s mean daily weight gain decreased from 1.27 to 0.66 grams per kilogram per day (g/kg/day) in the intervention group and 0.77 to 0.49 g/kg/day in the controls after adjusting for age differences between the two groups from baseline to five months of follow up. The mean monthly height gain decreased from 1.13 to 1.03 millimeters per metre per month in the intervention children and 1.26 to 1.01 in the controls. The weight gain was highest in the intervention children who were most wasted at baseline and the controls who were least stunted. Conclusion The children showed suboptimal growth despite food supplements, highlighting the need for ongoing research to develop inexpensive, locally-sourced food supplements to improve the nutrition of underweight children in Bangladesh. PMID:27415153

Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer?

PubMed

Kopelman, Tammy R; O'Neill, Patrick J; Pieri, Paola G; Salomone, Jeffrey P; Hall, Scott T; Quan, Asia; Wells, Jordan R; Pressman, Melissa S

2013-12-01

Inadequate anti-factor Xa levels and increased venous thromboembolic events occur in trauma patients receiving standard prophylactic enoxaparin dosing. The aim of this study was to test the hypothesis that higher dosing (40 mg twice daily) would improve peak anti-Xa levels and decrease venous thromboembolism. A retrospective review was performed of trauma patients who received prophylactic enoxaparin and peak anti-Xa levels over 27 months. Patients were divided on the basis of dose: group A received 30 mg twice daily, and group B received 40 mg twice daily. Demographics and rates of venous thromboembolism were compared between dose groups and patients with inadequate or adequate anti-Xa levels. One hundred twenty-four patients were included, 90 in group A and 34 in group B. Demographics were similar, except that patients in group B had a higher mean body weight. Despite this, only 9% of group B patients had inadequate anti-Xa levels, compared with 33% of those in group A (P = .01). Imaging studies were available in 69 patients and revealed 8 venous thromboembolic events (P = NS, group A vs group B) with significantly more venous thromboembolic events occurring in patients with low anti-Xa levels (P = .02). Although higher dosing of enoxaparin led to improved anti-Xa levels, this did not equate to a statistical decrease in venous thromboembolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Hypofractionated Prostate Radiotherapy with or without Conventionally Fractionated Nodal Irradiation: Clinical Toxicity Observations and Retrospective Daily Dosimetry.

PubMed

McDonald, Andrew M; Bishop, Justin M; Jacob, Rojymon; Dobelbower, Michael C; Kim, Robert Y; Yang, Eddy S; Smith, Heather; Wu, Xingen; Fiveash, John B

2012-01-01

Purpose. To evaluate toxicity associated with the addition of elective nodal irradiation (ENI) to a hypofractionated regimen for the treatment of prostate cancer. Methods and Materials. Fifty-seven patients received pelvic image-guided IMRT to 50.4 Gy in 28 fractions with a hypofractionated simultaneous boost to the prostate to 70 Gy. Thirty-one patients received prostate-only treatment to 70 Gy in 28 fractions. Results. Median followup was 41.1 months. Early grade ≥2 urinary toxicity rates were 49% (28 of 57) for patients receiving ENI and 58% (18 of 31) for those not (P = 0.61). Early grade ≥2 rectal toxicity rates were 40% (23 of 57) and 23% (7 of 31), respectively (P = 0.09). The addition of ENI resulted in a 21% actuarial rate of late grade ≥2 rectal toxicity at 4 years, compared to 0% for patients treated to the prostate only (P = 0.02). Retrospective daily dosimetry of patients experiencing late rectal toxicity revealed an average increase of 2.67% of the rectal volume receiving 70 Gy compared to the original plan. Conclusions. The addition of ENI resulted in an increased risk of late rectal toxicity. Grade ≥2 late rectal toxicity was associated with worse daily rectal dosimetry compared to the treatment plan.

Electroacupuncture reduces duration of postoperative ileus after laparoscopic surgery for colorectal cancer.

PubMed

Ng, Simon S M; Leung, Wing Wa; Mak, Tony W C; Hon, Sophie S F; Li, Jimmy C M; Wong, Cherry Y N; Tsoi, Kelvin K F; Lee, Janet F Y

2013-02-01

We investigated the efficacy of electroacupuncture in reducing the duration of postoperative ileus and hospital stay after laparoscopic surgery for colorectal cancer. We performed a prospective study of 165 patients undergoing elective laparoscopic surgery for colonic and upper rectal cancer, enrolled from October 2008 to October 2010. Patients were assigned randomly to groups that received electroacupuncture (n = 55) or sham acupuncture (n = 55), once daily from postoperative days 1-4, or no acupuncture (n = 55). The acupoints Zusanli, Sanyinjiao, Hegu, and Zhigou were used. The primary outcome was time to defecation. Secondary outcomes included postoperative analgesic requirement, time to ambulation, and length of hospital stay. Patients who received electroacupuncture had a shorter time to defecation than patients who received no acupuncture (85.9 ± 36.1 vs 122.1 ± 53.5 h; P < .001) and length of hospital stay (6.5 ± 2.2 vs 8.5 ± 4.8 days; P = .007). Patients who received electroacupuncture also had a shorter time to defecation than patients who received sham acupuncture (85.9 ± 36.1 vs 107.5 ± 46.2 h; P = .007). Electroacupuncture was more effective than no or sham acupuncture in reducing postoperative analgesic requirement and time to ambulation. In multiple linear regression analysis, an absence of complications and electroacupuncture were associated with a shorter duration of postoperative ileus and hospital stay after the surgery. In a clinical trial, electroacupuncture reduced the duration of postoperative ileus, time to ambulation, and postoperative analgesic requirement, compared with no or sham acupuncture, after laparoscopic surgery for colorectal cancer. ClinicalTrials.gov number, NCT00464425. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Daily negative affect and smoking after a self-set quit attempt: The role of dyadic invisible social support in a daily diary study.

PubMed

Lüscher, Janina; Stadler, Gertraud; Ochsner, Sibylle; Rackow, Pamela; Knoll, Nina; Hornung, Rainer; Scholz, Urte

2015-11-01

Social support receipt from one's partner is assumed to be beneficial for successful smoking cessation. However, support receipt can have costs. Recent research suggests that the most effective support is unnoticed by the receiver (i.e., invisible). Therefore, this study examined the association between everyday levels of dyadic invisible emotional and instrumental support, daily negative affect, and daily smoking after a self-set quit attempt in smoker-non-smoker couples. Overall, 100 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date on for 22 consecutive days, reporting daily invisible emotional and instrumental social support, daily negative affect, and daily smoking. Same-day multilevel analyses showed that at the between-person level, higher individual mean levels of invisible emotional and instrumental support were associated with less daily negative affect. In contrast to our assumption, more receipt of invisible emotional and instrumental support was related to more daily cigarettes smoked. The findings are in line with previous results, indicating invisible support to have beneficial relations with affect. However, results emphasize the need for further prospective daily diary approaches for understanding the dynamics of invisible support on smoking cessation. Statement of contribution What is already known on this subject? Social support receipt from a close other has proven to have emotional costs. According to current studies, the most effective social support is unnoticed by the receiver (i.e., invisible). There is empirical evidence for beneficial effects of invisible social support on affective well-being. What does this study add? Confirming benefits of invisible social support for negative affect in a health behaviour change setting Providing first evidence for detrimental effects of invisible social support on smoking. © 2015 The British Psychological Society.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

PubMed

Narula, Neeraj; Cooray, Mohan; Anglin, Rebecca; Muqtadir, Zack; Narula, Alisha; Marshall, John K

2017-02-01

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. NCT02615288.

Dilantin therapy in an experimental model of traumatic brain injury: effects of limited versus daily treatment on neurological and behavioral recovery.

PubMed

Darrah, Shaun D; Darrah, Shaun H; Chuang, Jerry; Mohler, Laura M; Chen, Xiangbai; Cummings, Erin E; Burnett, Tiffany; Reyes-Littaua, M Christina; Galang, Gary N; Wagner, Amy K

2011-01-01

The mechanisms by which Dilantin confers anticonvulsant benefits may also be neuroprotective by attenuating the acute excitatory insult in cortical and subcortical structures when the drug is given in the acute phase after traumatic brain injury (TBI). However, when Dilantin is used for prolonged periods, we hypothesized that it may impede recovery, synaptic plasticity may be impaired, and neuroprotective benefits may be lost. As such, we assessed the effect of daily chronic administration (75 mg/kg day 0 followed by 50 mg/kg daily i.p.) and acute administration (75 mg/kg day 0 followed by 50 mg/kg i.p. day 1) of Dilantin in young adult male rats on motor performance, y-maze exploration, Morris Water Maze (MWM), hippocampal (HC) cell survival, contusion size, and regional expression of neuroplasticity markers after controlled cortical impact (CCI) injury. Chronic daily Dilantin administration resulted in beam walking impairments on day 6, whereas acute Dilantin administration resulted in beam walking impairments on days 3 and 4. Chronic Dilantin administration also resulted in worse MWM performance, more HC cell loss and no increases in neuroplasticity markers compared to rats with CCI receiving chronic vehicle. Conversely, rats receiving acute Dilantin administration exhibited more novel arm exploration in the y-maze, greater HC cell sparing, and greater growth-associated protein 43 (GAP-43) expression in the HC ipsilateral to the CCI, compared to injured rats receiving vehicle. MWM was not influenced by acute Dilantin administration. These results suggest that there are beneficial effects of limited acute Dilantin therapy after TBI, and that extended daily Dilantin therapy has deleterious effects on neural recovery. These findings support clinical guidelines for limited use of Dilantin in seizure prophylaxis after TBI.

De novo kidney transplant recipients need higher doses of Advagraf compared with Prograf to get therapeutic levels.

PubMed

Crespo, M; Mir, M; Marin, M; Hurtado, S; Estadella, C; Gurí, X; Rap, O; Moral, R; Puig, J M; Lloveras, J

2009-01-01

Advagraf is a new modified-release once-daily formulation of tacrolimus with a similar efficacy and safety profile to twice-daily tacrolimus (Prograf) according to clinical trials. Few data are published about its use in clinical practice, outside of sponsored clinical trials. We compared efficacy and basic pharmacokinetics of once-daily and twice-daily tacrolimus in de novo renal transplantation. The Advagraf group included 26 de novo renal cases who had received initial immunosuppression with once-daily tacrolimus (0.2 mg/kg from day 1 posttransplantation) combined with mycophenolic acid, steroids, and anti-CD25 monoclonal antibodies (2 doses). We compared them with a Prograf group of 26 transplants performed immediately before, who received equivalent immunosuppression with twice-daily tacrolimus (0.2 mg/kg from day 1). We did not observe significant differences between groups in demographics, efficacy, and basic pharmacokinetics, namely, tacrolimus trough levels at 7, 15, 30, 60, or 90 days. We found that recipients on Advagraf needed significantly higher tacrolimus doses per kg up to 6 months post-transplantation than those on Prograf: 0.16 vs 0.11; 0.14 vs 0.08; and 0.12 vs 0.08 mg/kg at 1, 3, and 6 months. No patient suffered severe liver dysfunction. There were no differences between groups in the administration of drugs interacting with CYP3A4 or prokinetics, which could alter tacrolimus pharmacokinetics. Among de novo renal cases, the new once-daily formulation of tacrolimus offered a similar short-term efficacy profile as the twice-daily tacrolimus. But it was necessary to use up to a 50% higher dose of Advagraf than Prograf to achieve similar trough levels during the first 6 months.

Transient simulation of molten salt central receiver

NASA Astrophysics Data System (ADS)

Doupis, Dimitri; Wang, Chuan; Carcorze-Soto, Jorge; Chen, Yen-Ming; Maggi, Andrea; Losito, Matteo; Clark, Michael

2016-05-01

Alstom is developing concentrated solar power (CSP) utilizing 60/40wt% NaNO3-KNO3 molten salt as the working fluid in a tower receiver for the global renewable energy market. In the CSP power generation cycle, receivers undergo a daily cyclic operation due to the transient nature of solar energy. Development of robust and efficient start-up and shut-down procedures is critical to avoiding component failures due to mechanical fatigue resulting from thermal transients, thus maintaining the performance and availability of the CSP plant. The Molten Salt Central Receiver (MSCR) is subject to thermal transients during normal daily operation, a cycle that includes warmup, filling, operation, draining, and shutdown. This paper describes a study to leverage dynamic simulation and finite element analysis (FEA) in development of start-up, shutdown, and transient operation concepts for the MSCR. The results of the FEA also verify the robustness of the MSCR design to the thermal transients anticipated during the operation of the plant.

Relationships between Lifestyle, Living Environments, and Incidence of Hypertension in Japan (in Men): Based on Participant’s Data from the Nationwide Medical Check-Up

PubMed Central

Oka, Mayumi; Yamamoto, Mio; Mure, Kanae; Takeshita, Tatsuya; Arita, Mikio

2016-01-01

This study aims to investigate factors that contribute to the differences in incidence of hypertension between different regions in Japan, by accounting for not only individual lifestyles, but also their living environments. The target participants of this survey were individuals who received medical treatment for hypertension, as well as hypertension patients who have not received any treatment. The objective variable for analysis was the incidence of hypertension as data aggregated per prefecture. We used data (in men) including obesity, salt intake, vegetable intake, habitual alcohol consumption, habitual smoking, and number of steps walked per day. The variables within living environment included number of rail stations, standard/light vehicle usage, and slope of habitable land. In addition, we analyzed data for the variables related to medical environment including, participation rate in medical check-ups and number of hospitals. We performed multiple stepwise regression analyses to elucidate the correlation of these variables by using hypertension incidence as the objective variable. Hypertension incidence showed a significant negative correlation with walking and medical check-ups, and a significant positive correlation with light-vehicle usage and slope. Between the number of steps and variables related to the living environment, number of rail stations showed a significant positive correlation, while, standard- and light-vehicle usage showed significant negative correlation. Moreover, with stepwise multiple regression analysis, walking showed the strongest effect. The differences in daily walking based on living environment were associated with the disparities in the hypertension incidence in Japan. PMID:27788198

Effect of visual biofeedback cycling training on gait in patients with multiple sclerosis.

PubMed

Hochsprung, A; Granja Domínguez, A; Magni, E; Escudero Uribe, S; Moreno García, A

2017-09-06

Gait alterations are present in a high percentage of patients with multiple sclerosis (MS). They appear from early stages of the disease and can limit patients' capacity to perform basic activities of daily living, affecting their quality of life. Visual biofeedback cycling training appears to be a useful tool in treating these impairments. This study aims to evaluate the short-term effect of visual biofeedback cycling training on gait in patients with MS. A total of 61 patients with mild to moderate MS were randomly assigned to a control group and an intervention group. The intervention group received visual biofeedback cycling training (MOTOmed viva2 system) once per week for 3 months, and a home exercise program. The control group only received the home exercise program. Both groups were evaluated using the GAITRite ® Walkway gait assessment system before the intervention, during the first month of the programme, and after the intervention. In the intervention group, the analysis revealed statistically significant differences between Functional Ambulation Profile (FAP) scores before and during the intervention (P=.014), and before and after the intervention (P=.002). A statistically significant improvement was observed in step length in the intervention group between pre- and post-intervention scores (P=.001) and between first-month and post-intervention scores (P=.004). Visual biofeedback cycling training improved specific gait parameters in the short term and appears to be a therapeutic option for gait retraining in patients with MS. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study.

PubMed

Sørensen, P S; Sellebjerg, F; Lycke, J; Färkkilä, M; Créange, A; Lund, C G; Schluep, M; Frederiksen, J L; Stenager, E; Pfleger, C; Garde, E; Kinnunen, E; Marhardt, K

2016-05-01

Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy. © 2016 EAN.

Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria.

PubMed

Smolen, Josef S; Aletaha, Daniel; Gruben, David; Zwillich, Samuel H; Krishnaswami, Sriram; Mebus, Charles

2017-04-01

Tofacitinib is an oral JAK inhibitor that is used for the treatment of rheumatoid arthritis (RA). In previous clinical trials of tofacitinib, a Disease Activity Score in 28 joints (DAS28)-based analysis was used to assess outcomes. In this study, remission rates according to various remission criteria were evaluated across 5 phase III randomized controlled studies. In all 5 studies, tofacitinib was administered at a dosage of 5 mg twice daily or 10 mg twice daily, either as monotherapy or with background methotrexate or other conventional synthetic disease-modifying antirheumatic drugs. One of the studies included adalimumab 40 mg once every 2 weeks. In addition to the 4-variable DAS28 using the erythrocyte sedimentation rate (DAS28-4[ESR]), a primary efficacy variable used in the phase III studies, disease activity was assessed post hoc by the 4-variable DAS28 using the C-reactive protein level (DAS28-4[CRP]), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and Boolean-based assessment. A total of 3,306 patients were analyzed (1,213 of these patients received tofacitinib 5 mg twice daily, 1,212 received tofacitinib 10 mg twice daily, 679 received placebo, and 202 received adalimumab 40 mg every 2 weeks). Remission rates varied according to the criteria used, with higher rates in the active-treatment groups for the DAS28-4(CRP) than for other scores. At month 3, remission rates with tofacitinib 5 mg twice daily were 18-22% using the DAS28-4(CRP), 5-10% using the DAS28-4(ESR), 4-7% using the SDAI, 5-6% using the CDAI, and 2-7% using the Boolean-based method. In contrast, the remission rates with placebo varied from 0% to 7%, with small differences between the DAS28-4(ESR) and the DAS28-4(CRP). Although tofacitinib at dosages of 5 mg twice daily and 10 mg twice daily was effective compared with placebo in achieving disease remission, regardless of the disease activity measure, remission rates were substantially higher when the DAS28-4(CRP) was used. The presence or absence and type of acute-phase reactants in remission criteria were significant contributors to remission rates across treatment groups. This finding has important consequences for trial design and clinical practice. © 2016, The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Multiple oral dosing of ketoconazole increases dog exposure to ivermectin.

PubMed

Hugnet, Christophe; Lespine, Anne; Alvinerie, Michel

2007-01-01

The parasiticide ivermectin and the antimicrobial drug ketoconazole are macrolides that interact with P-glycoprotein. We investigated the effects of ketoconazole at a clinical dose on the pharmacokinetics of ivermectin, a CYP3A substrate with low hepatic clearance. Beagle dogs received a single subcutaneous injection of ivermectin at 0.05 mg/kg alone (n=6) or in combination with a daily oral dose of ketoconazole 10 mg/kg over 5 days before and after ivermectin administration (n=6). The plasma kinetics of ivermectin and its metabolite were followed over 15 days by HPLC analysis. Co-administered ketoconazole induced a higher plasma concentration and longer residence time of ivermectin in dogs, leading to a substantial increase in the overall exposure of the animal to the drug. Ketoconazole does not interfere with the production of the ivermectin metabolite but it may rather inhibit the elimination of the parental drug by interfering with P-gp transport. Multiple oral dosing of ketoconazole dramatically altered the pharmacokinetics of ivermectin in dogs leading to an increase in systemic exposure to the drug. Neurotoxicity of ivermectin means that inhibition of the P-gp function at the blood-brain barrier during polytherapy using P-gp inhibitors must be taken into consideration.

Pharmacokinetics and Safety of MP-376 (Levofloxacin Inhalation Solution) in Cystic Fibrosis Subjects▿

PubMed Central

Geller, David E.; Flume, Patrick A.; Griffith, David C.; Morgan, Elizabeth; White, Dan; Loutit, Jeffery S.; Dudley, Michael N.

2011-01-01

The pharmacokinetics and tolerability of nebulized MP-376 (levofloxacin inhalation solution [Aeroquin]) were determined in cystic fibrosis (CF) subjects. Ten CF subjects received single 180-mg doses of two formulations of MP-376, followed by a multiple-dose phase of 240 mg once daily for 7 days. Serum and expectorated-sputum samples were assayed for levofloxacin content. Safety was evaluated following the single- and multiple-dose study phases. Nebulized MP-376 produced high concentrations of levofloxacin in sputum. The mean maximum plasma concentration (Cmax) ranged between 2,563 and 2,932 mg/liter for 180-mg doses of the 50- and 100-mg/ml formulations, respectively. After 7 days of dosing, the mean Cmax for the 240-mg dose was 4,691 mg/liter. The mean serum levofloxacin Cmax ranged between 0.95 and 1.28 for the 180-mg doses and was 1.71 for the 240-mg dose. MP-376 was well tolerated. Nebulized MP-376 produces high sputum and low serum levofloxacin concentrations. The pharmacokinetics, safety, and tolerability were similar for the two formulations. MP-376 240 mg (100 mg/ml) is being advanced into late-stage clinical development. PMID:21444699

Gamma-band activation predicts both associative memory and cortical plasticity

PubMed Central

Headley, Drew B.; Weinberger, Norman M.

2011-01-01

Gamma-band oscillations are a ubiquitous phenomenon in the nervous system and have been implicated in multiple aspects of cognition. In particular, the strength of gamma oscillations at the time a stimulus is encoded predicts its subsequent retrieval, suggesting that gamma may reflect enhanced mnemonic processing. Likewise, activity in the gamma-band can modulate plasticity in vitro. However, it is unclear whether experience-dependent plasticity in vivo is also related to gamma-band activation. The aim of the present study is to determine whether gamma activation in primary auditory cortex modulates both the associative memory for an auditory stimulus during classical conditioning and its accompanying specific receptive field plasticity. Rats received multiple daily sessions of single tone/shock trace and two-tone discrimination conditioning, during which local field potentials and multiunit discharges were recorded from chronically implanted electrodes. We found that the strength of tone-induced gamma predicted the acquisition of associative memory 24 h later, and ceased to predict subsequent performance once asymptote was reached. Gamma activation also predicted receptive field plasticity that specifically enhanced representation of the signal tone. This concordance provides a long-sought link between gamma oscillations, cortical plasticity and the formation of new memories. PMID:21900554

Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia: clinical and physiological effects

PubMed Central

Kimberley, Teresa Jacobson; Borich, Michael R.; Arora, Sanjeev; Siebner, Hartwig R.

2016-01-01

Purpose The ability of low-frequency repetitive transcranial magnetic stimulation (rTMS) to enhance intracortical inhibition has motivated its use as a potential therapeutic intervention in focal hand dystonia (FHD). In this preliminary investigation, we assessed the physiologic and behavioral effects of multiple sessions of rTMS in FHD. Methods 12 patients with FHD underwent five daily-sessions of 1Hz rTMS to contralateral dorsal premotor cortex (dPMC). Patients held a pencil and made movements that did not elicit dystonic symptoms during rTMS. We hypothesized that an active but non-dystonic motor state would increase beneficial effects of rTMS. Five additional patients received sham-rTMS protocol. The area under curve (AUC) of the motor evoked potentials and the cortical silent period (CSP) were measured to assess changes in corticospinal excitability and intracortical inhibition, respectively. Behavioral measures included pen force and velocity during handwriting and subjective report. Results Multiple-session rTMS strengthened intracortical inhibition causing a prolongation of CSP after 3 days of intervention and pen force was reduced at day 1 and 5, leaving other measures unchanged. 68% of patients self-reported as ‘responders’ at day 5, and 58% at follow-up. Age predicted responders. Conclusions A strong therapeutic potential of this rTMS paradigm in FHD was not supported but findings warrant further investigation. PMID:23340117

Responses of Spartina alterniflora to Multiple Stressors ...

EPA Pesticide Factsheets

Coastal wetlands, well recognized for their ecosystem services, have faced many threats throughout the United States and elsewhere. Managers require good information on responses of wetlands to the combined stressors that these habitats experience, or may in the future as a result of climate change, and few studies have explored the effect of multiple stressors on wetlands. We conducted a 4-month mesocosm study to analyze the multiple stressor effects of precipitation changes, sea level rise, and eutrophication on the salt marsh plant Spartina alterniflora. Pots containing plants in a soil matrix were positioned in tanks and received Narragansett Bay (RI) water. The mesocosms simulated three precipitation levels (ambient daily rain, biweekly storm, and drought); three elevation levels, low (15 cm below mean high water (MHW)), middle (MHW), and high (15 cm above MHW); and two nutrient enrichment levels (unenriched and nutrient-enriched bay water). Our results demonstrate storm and drought stressors led to significantly less above- and belowground biomass than those in ambient rain conditions. Plants that were flooded at the low elevation had less belowground biomass, fine roots, and S. alterniflora shoots. Nutrients had no detectable effect on total above- and belowground biomass, but the enriched pots had higher stem counts and more fine roots than unenriched pots, in addition to greater CO2 emission rates. However, the unenriched pots had significantly more co

Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1).

PubMed

Westhovens, R; Taylor, P C; Alten, R; Pavlova, D; Enríquez-Sosa, F; Mazur, M; Greenwald, M; Van der Aa, A; Vanhoutte, F; Tasset, C; Harrison, P

2017-06-01

To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX. In this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response. Overall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100  or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported. Filgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated. NCT01888874. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Incidence of deep vein thrombosis is increased with 30 mg twice daily dosing of enoxaparin compared with 40 mg daily.

PubMed

Riha, Gordon M; Van, Philbert Y; Differding, Jerome A; Schreiber, Martin A

2012-05-01

The purpose of this study was to analyze whether 2 standard dosing regimens of enoxaparin (30 mg twice daily vs 40 mg once daily) would result in different deep vein thrombosis (DVT) rates and anti-factor Xa activity (anti-Xa) in surgical patients. Patients who required enoxaparin for prophylaxis were followed prospectively. Demographics were recorded. Patients underwent standardized duplex screening. Peak anti-Xa levels were drawn on 4 consecutive days. Sixty-three patients were followed up (28 patients on 30 mg twice daily, 35 patients on 40 mg once daily). There was no significant difference in demographics between groups. Twenty-five percent of patients on 30 mg twice daily developed a DVT, whereas 2.9% of patients on 40 mg once daily developed a DVT. Patients on 30 mg twice daily had significantly lower anti-Xa levels. The incidence of DVT is increased in surgical patients who receive 30 mg twice daily dosing of enoxaparin compared with 40 mg daily. Dosing of 40 mg once daily results in significantly higher peak anti-Xa levels compared with 30 mg twice daily. Copyright © 2012 Elsevier Inc. All rights reserved.

Quality of life and patient preferences: identification of subgroups of multiple sclerosis patients.

PubMed

Rosato, Rosalba; Testa, Silvia; Oggero, Alessandra; Molinengo, Giorgia; Bertolotto, Antonio

2015-09-01

The aim of this study was to estimate preferences related to quality of life attributes in people with multiple sclerosis, by keeping heterogeneity of patient preference in mind, using the latent class approach. A discrete choice experiment survey was developed using the following attributes: activities of daily living, instrumental activities of daily living, pain/fatigue, anxiety/depression and attention/concentration. Choice sets were presented as pairs of hypothetical health status, based upon a fractional factorial design. The latent class logit model estimated on 152 patients identified three subpopulations, which, respectively, attached more importance to: (1) the physical dimension; (2) pain/fatigue and anxiety/depression; and (3) instrumental activities of daily living impairments, anxiety/depression and attention/concentration. A posterior analysis suggests that the latent class membership may be related to an individual's age to some extent, or to diagnosis and treatment, while apart from energy dimension, no significant difference exists between latent groups, with regard to Multiple Sclerosis Quality of Life-54 scales. A quality of life preference-based utility measure for people with multiple sclerosis was developed. These utility values allow identification of a hierarchic priority among different aspects of quality of life and may allow physicians to develop a care programme tailored to patient needs.

Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

Isaacson, Stuart; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J; Kalu, Uwa; White, William B

2016-10-01

The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days). Rates of serious adverse events (AEs), cardiac-related AEs, and supine hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a cardiovascular nature, were not attributed by investigators to droxidopa. In this large cohort of patients with neurogenic orthostatic hypotension, droxidopa was well tolerated during long-term use. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

PubMed Central

Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru

2010-01-01

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762

VAST Challenge 2014: The Kronos Incident

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whiting, Mark A.; Cook, Kristin A.; Grinstein, Georges

2014-10-31

The 2014 IEEE Visual Analytics Science and Technology (VAST) Challenge presented researchers with a single fictitious scenario: the disappearance of staff members of the GASTech oil and gas company on location on the island of Kronos. A group named the Protectors of Kronos (POK) was the prime suspect in the disappearance. Three mini-challenges and a grand challenge were offered. Mini-challenge 1 included multiple types of text data for participants to provide a timeline of key events and characterize the POK, mini-challenge 2 focused on individuals’ movement and financial data for participants to provide patterns of daily life, and mini-challenge 3more » featured real-time streaming social media and emergency service data for participants to provide hostage and kidnapper information. The grand challenge asked the participants to integrate results and generate a synopsis of events. The VAST Challenge received 73 submissions from 13 countries« less

Training multitasking in a virtual supermarket: a novel intervention after stroke.

PubMed

Rand, Debbie; Weiss, Patrice L Tamar; Katz, Noomi

2009-01-01

To explore the potential of the VMall, a virtual supermarket running on a video-capture virtual reality system, as an intervention tool for people who have multitasking deficits after stroke. Poststroke, 4 participants received ten 60-min sessions over 3 weeks using the VMall. The intervention focused on improving multitasking while the participant was engaged in a virtual shopping task. Instruments included the Multiple Errands Test-Hospital Version (MET-HV) in a real mall and in the VMall. Participants achieved improvements ranging from 20.5% to 51.2% for most of the MET-HV measures performed in a real shopping mall and in the VMall. The data support the VMall's potential as a motivating and effective intervention tool for the rehabilitation of people poststroke who have multitasking deficits during the performance of daily tasks. However, because the sample was small, additional intervention studies with the VMall should be conducted.

Protective Effect of Propolis in Proteinuria, Crystaluria, Nephrotoxicity and Hepatotoxicity Induced by Ethylene Glycol Ingestion.

PubMed

El Menyiy, Nawal; Al Waili, Noori; Bakour, Meryem; Al-Waili, Hamza; Lyoussi, Badiaa

2016-10-01

Propolis is a natural honeybee product with wide biological activities and potential therapeutic properties. The aim of the study is to evaluate the protective effect of propolis extract on nephrotoxicity and hepatotoxicity induced by ethylene glycol in rats. Five groups of rats were used. Group 1 received drinking water, group 2 received 0.75% ethylene-glycol in drinking water, group 3 received 0.75% ethylene-glycol in drinking water along with cystone 500 mg/kg/body weight (bw) daily, group 4 received 0.75% ethylene-glycol in drinking water along with propolis extract at a dose of 100 mg/kg/bw daily, and group 5 received 0.75% ethylene-glycol in drinking water along with propolis extract at a dose of 250 mg/kg/bw daily. The treatment continued for a total of 30 d. Urinalyses for pH, crystals, protein, creatinine, uric acid and electrolytes, and renal and liver function tests were performed. Ethylene-glycol increased urinary pH, urinary volume, and urinary calcium, phosphorus, uric acid and protein excretion. It decreased creatinine clearance and magnesium and caused crystaluria. Treatment with propolis extract or cystone normalized the level of magnesium, creatinine, sodium, potassium and chloride. Propolis is more potent than cystone. Propolis extract alleviates urinary protein excretion and ameliorates the deterioration of liver and kidney function caused by ethylene glycol. Propolis extract has a potential protective effect against ethylene glycol induced hepatotoxicity and nephrotoxicity and has a potential to treat and prevent urinary calculus, crystaluria and proteinuria. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Bacillus Calmette-Guérin with or without interferon α-2b and megadose versus recommended daily allowance vitamins during induction and maintenance intravesical treatment of nonmuscle invasive bladder cancer.

PubMed

Nepple, Kenneth G; Lightfoot, Andrew J; Rosevear, Henry M; O'Donnell, Michael A; Lamm, Donald L

2010-11-01

In a multicenter, prospectively randomized study we evaluated bacillus Calmette-Guérin alone vs bacillus Calmette-Guérin plus interferon α-2b and megadose vitamins vs recommended daily allowance vitamins during induction and maintenance intravesical therapy in the treatment of nonmuscle invasive bladder cancer. Patients who were bacillus Calmette-Guérin naïve with carcinoma in situ, Ta or T1 urothelial cancer were randomized to receive intravesical bacillus Calmette-Guérin or bacillus Calmette-Guérin plus interferon α-2b. Patients were further randomized to receive a recommended daily allowance or megadose vitamin preparation. Induction bacillus Calmette-Guérin treatment was given weekly for 6 weeks, and patients who were recurrence-free received maintenance treatment at 4, 7, 13, 19, 25 and 37 months. Patients were followed with quarterly cystoscopy for 2 years, then semiannually through year 4 and then annually. The primary end point was biopsy confirmed tumor recurrence or positive cytology. A total of 670 patients were accrued and randomized. At 24-month median followup recurrence-free survival was similar in all groups with 63% in the bacillus Calmette-Guérin with recommended daily allowance vitamins group, 59% in bacillus Calmette-Guérin with megadose vitamins, 55% in bacillus Calmette-Guérin/interferon α-2b with recommended daily allowance vitamins and 61% in bacillus Calmette-Guérin/interferon α-2b with megadose vitamins (p >0.05). The addition of interferon α-2b was associated with a more frequent incidence of fever (11% vs 5%) and constitutional symptoms (18% vs 11%) vs bacillus Calmette-Guérin alone (p <0.05). Interferon α-2b added to bacillus Calmette-Guérin induction and maintenance intravesical therapy did not decrease tumor recurrence in bacillus Calmette-Guérin naïve cases, but was associated with increased fever and constitutional symptoms. No difference in time to recurrence was present in patients receiving recommended daily allowance vs high dose vitamins. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Toward daily monitoring of vegetation conditions at field scale through fusing data from multiple sensors

USDA-ARS?s Scientific Manuscript database

Vegetation monitoring requires remote sensing data at fine spatial and temporal resolution. While imagery from coarse resolution sensors such as MODIS/VIIRS can provide daily observations, they lack spatial detail to capture surface features for crop and rangeland monitoring. The Landsat satellite s...

MULTIVARIATE STATISTICAL MODELS FOR EFFECTS OF PM AND COPOLLUTANTS IN A DAILY TIME SERIES EPIDEMIOLOGY STUDY

EPA Science Inventory

Most analyses of daily time series epidemiology data relate mortality or morbidity counts to PM and other air pollutants by means of single-outcome regression models using multiple predictors, without taking into account the complex statistical structure of the predictor variable...

A double-blind, randomized, placebo-controlled study of cevimeline in Sjögren's syndrome patients with xerostomia and keratoconjunctivitis sicca.

PubMed

Petrone, Dianne; Condemi, John J; Fife, Rose; Gluck, Oscar; Cohen, Stanley; Dalgin, Paul

2002-03-01

To evaluate the safety and efficacy of 2 dosages of cevimeline for the treatment of xerostomia and keratoconjunctivitis sicca in patients with Sjögren's syndrome. A 12-week double-blind, randomized, placebo-controlled study was performed. Patients were randomly assigned to receive either placebo, 15 mg of cevimeline 3 times daily, or 30 mg of cevimeline 3 times daily. Patients were evaluated at baseline and throughout the study for their global assessment of dryness (mouth, eyes, overall) as well as their subjective assessment of the specific symptoms of dry mouth and dry eyes. Total saliva and tear flow also were measured. Patients taking 30 mg of cevimeline 3 times daily had statistically significant improvements in their subjective global assessment of dry eyes (P = 0.0453), dry mouth (P = 0.0004), and increased salivary flow (P = 0.007). Patients receiving the 30-mg dosage also showed greater objective improvement (increased salivary and lacrimal flow rates, as measured by Schirmer's test) than did patients receiving placebo. Frequently reported adverse events included headache, increased sweating, abdominal pain, and nausea. Treatment with cevimeline at a dosage of 30 mg 3 times daily resulted in substantive improvement by increasing the rate of saliva and tear flow in patients with Sjögren's syndrome, as well as improving subjective symptoms of dry mouth, dry eyes, and overall dryness. The 15-mg dosage relieved some symptoms, and both dosages were well tolerated.

The Effect of Randomized Homework Contingencies on College Students' Daily Homework and Unit Exam Performance

ERIC Educational Resources Information Center

Galyon, Charles E.; Voils, Kyle L.; Blondin, Carolyn A.; Williams, Robert L.

2015-01-01

Students in an introductory educational psychology course submitted answers to daily homework questions for which they received credit either for percentage of questions answered in every homework assignment or for the accuracy of their answers to 10% of randomly selected questions. Potential credit was the same under both homework contingencies,…

Dissociation between the pharmacokinetics and pharmacodynamics of once-daily rivaroxaban and twice-daily apixaban: a randomized crossover study.

PubMed

Kreutz, R; Persson, P B; Kubitza, D; Thelen, K; Heitmeier, S; Schwers, S; Becka, M; Hemmrich, M

2017-10-01

Essentials In this crossover study the anticoagulant effects of rivaroxaban and apixaban were compared. Healthy volunteers received rivaroxaban 20 mg once daily or apixaban 5 mg twice daily. Rivaroxaban was associated with more prolonged inhibition of thrombin generation than apixaban. Rivaroxaban induced a clear prolongation of prothrombin time and activated partial thromboplastin time. Background The anticoagulant actions of the oral direct activated factor Xa inhibitors, rivaroxaban and apixaban, have not previously been directly compared. Objectives To compare directly the steady-state pharmacokinetics and anticoagulant effects of rivaroxaban and apixaban at doses approved for stroke prevention in patients with non-valvular atrial fibrillation. Methods Twenty-four healthy Caucasian male volunteers were included in this open-label, two-period crossover, phase 1 study (EudraCT number: 2015-002612-32). Volunteers were randomized to receive rivaroxaban 20 mg once daily or apixaban 5 mg twice daily for 7 days, followed by a washout period of at least 7 days before they received the other treatment. Plasma concentrations and anticoagulant effects were measured at steady state and after drug discontinuation. Results Overall exposure was similar for both drugs: the geometric mean area under the plasma concentration-time curve for the 0-24-h interval was 1830 μg h L -1 for rivaroxaban and 1860 μg h L -1 for apixaban. Rivaroxaban was associated with greater inhibition of endogenous thrombin potential (geometric mean area under the curve relative to baseline during the 0-24-h interval: 15.5 h versus 17.5 h) and a more pronounced maximal prolongation relative to baseline of prothrombin time (PT) (1.66-fold versus 1.14-fold) and activated partial thromboplastin time (APTT) (1.43-fold versus 1.16-fold) at steady state than apixaban. Conclusions Despite similar exposure to both drugs, rivaroxaban 20 mg once daily was associated with greater and more sustained inhibition of thrombin generation than apixaban 5 mg twice daily. Sensitive PT and APTT assays can be used to estimate the anticoagulant effects of rivaroxaban. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

[Daily living activities and oral condition among care facility residents with severe intellectual disabilities. Comparative analyses between residents receiving tooth-brushing assistance and those not receiving tooth-brushing assistance].

PubMed

Chiwata, Kaoru; Takeda, Fumi

2007-06-01

To clarify 1) differences in daily living activities and oral condition among care facility residents with severe intellectual disabilities and 2) chronological changes in daily living activities and oral condition for residents receiving tooth-brushing assistance and those never receiving tooth-brushing assistance. Subjects were 44 residents at a care facility for individuals with severe intellectual disabilities, who underwent dental screening in July 1994 and October 2003. At each time point, daily living activities, behavior during oral health guidance, behavior during dental health screening and oral condition were compared between residents receiving tooth-brushing assistance (assistance group) and those not receiving tooth-brushing assistance (independent group). Furthermore, chronological changes were analyzed for residents requiring assistance at both screenings, those requiring assistance only at the second screening, and those not requiring assistance at either screening. 1) In the assistance group, 100% and 36.4% of residents were unable to brush their teeth independently in 1994 and 2003, respectively. Significant differences between the assistance and independent groups were observed in all items of behavior during dental health screening in 1994, but not in 2003. No significant intergroup differences in oral condition were observed in 1994, but differences were seen in 2003; when compared to the assistance group, the number of lost teeth was significantly higher in the independent group, while the number of remaining teeth was lower. 2) Regarding changes over the nine-year period, a significantly greater proportion of residents not requiring assistance at either screening and those requiring assistance only at the second screening finally required assistance in bathing. As for oral condition, no significant changes in healthy teeth were observed in residents requiring assistance at both screening time points, while significant increases in dental caries and filled teeth and a significant decrease in the number of healthy teeth were observed in residents requiring assistance only at the second screening and those not requiring assistance at either screening. Over the nine-year period, the subjects of tooth-brushing assistance changed, and assistance was given to those able to brush their teeth independently in addition to those unable to brush their teeth independently. The number of healthy teeth did not change in residents receiving tooth-brushing assistance during this period, but in residents never receiving tooth-brushing assistance, decrease was noted. Therefore, even for individuals able to brush their teeth independently, some form of tooth-brushing assistance is needed to sufficiently prevent oral diseases.

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease.

PubMed

Larsen, Sanne Bøjet; Grove, Erik Lerkevang; Neergaard-Petersen, Søs; Würtz, Morten; Hvas, Anne-Mette; Kristensen, Steen Dalby

2017-08-05

Increased platelet aggregation during antiplatelet therapy may predict cardiovascular events in patients with coronary artery disease. The majority of these patients receive aspirin monotherapy. We aimed to investigate whether high platelet-aggregation levels predict cardiovascular events in stable coronary artery disease patients treated with aspirin. We included 900 stable coronary artery disease patients with either previous myocardial infarction, type 2 diabetes mellitus, or both. All patients received single antithrombotic therapy with 75 mg aspirin daily. Platelet aggregation was evaluated 1 hour after aspirin intake using the VerifyNow Aspirin Assay (Accriva Diagnostics) and Multiplate Analyzer (Roche; agonists: arachidonic acid and collagen). Adherence to aspirin was confirmed by serum thromboxane B 2 . The primary end point was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At 3-year follow-up, 78 primary end points were registered. The primary end point did not occur more frequently in patients with high platelet-aggregation levels (first versus fourth quartile) assessed by VerifyNow (hazard ratio: 0.5 [95% CI, 0.3-1.1], P =0.08) or Multiplate using arachidonic acid (hazard ratio: 1.0 [95% CI, 0.5-2.1], P =0.92) or collagen (hazard ratio: 1.4 [95% CI, 0.7-2.8], P =0.38). Similar results were found for the composite secondary end point (nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and all-cause death) and the single end points. Thromboxane B 2 levels did not predict any end points. Renal insufficiency was the only clinical risk factor predicting the primary and secondary end points. This study is the largest to investigate platelet aggregation in stable coronary artery disease patients receiving aspirin as single antithrombotic therapy. We found that high platelet-aggregation levels did not predict cardiovascular events. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Social grooming among wild bonobos (Pan paniscus) at Wamba in the Luo Scientific Reserve, DR Congo, with special reference to the formation of grooming gatherings.

PubMed

Sakamaki, Tetsuya

2013-10-01

Chimpanzees (Pan troglodytes) groom in gatherings in which many individuals may be connected via multiple chains of grooming and they often exchange partners with each other. They sometimes groom another while receiving grooming; that is, one animal can play two roles (i.e., groomer and groomee) simultaneously. Although this feature of chimpanzees is notable from the viewpoint of the evolution of human sociality, information on our other closest living relative, the bonobo (Pan paniscus), is still lacking. In this study, I describe grooming interactions of bonobos at Wamba in the Luo Scientific Reserve, Democratic Republic of the Congo (DR Congo), with a particular focus on the formation of grooming gatherings. Like chimpanzees, the bonobos also performed mutual grooming (two individuals grooming each other simultaneously) and polyadic grooming (three or more individuals). However, unlike chimpanzees, these sessions lasted for only a short time. Bonobos rarely groomed another while receiving grooming. Because social grooming occurred not only in trees but also in open spaces, including treefall gaps, the conditions did not necessarily limit the opportunity to make multiple chains of grooming. However, bonobos also engaged in social grooming in different ways from chimpanzees; That is, many individuals were involved simultaneously at a site, in which they separated for dyadic grooming. Some cases clearly showed that bonobos preferred a third party not to join while grooming in a dyad, suggesting that bonobos have a preference for grooming in dyads and that immature individuals formed the preference that was shared among adults while growing up. Most members of the study group ranged together during the majority of the study period. Although bonobos show a fission-fusion grouping pattern, when group members frequently encounter one another on a daily basis, they may not be motivated to form multiple grooming chains at this site, as do chimpanzees.

Impact of 4.0% chlorhexidine cord cleansing on the bacteriologic profile of the newborn umbilical stump in rural Sylhet District, Bangladesh: a community-based, cluster-randomized trial.

PubMed

Mullany, Luke C; Saha, Samir K; Shah, Rasheduzzaman; Islam, Mohammad Shahidul; Rahman, Mostafiz; Islam, Maksuda; Talukder, Radwanur Rahman; El Arifeen, Shams; Darmstadt, Gary L; Baqui, Abdullah H

2012-05-01

Randomized trials from South Asia indicate umbilical cord chlorhexidine cleansing reduces mortality and omphalitis. No community-based data are available on bacteriological profile of the cord, early neonatal colonization dynamics, or impact of cord cleansing on colonizing organisms. Such data could clarify the design of scaled chlorhexidine interventions. Umbilical swabs were collected at home (days 1, 3, 6) after birth from infants participating in a trial of 3 cord-care regimens (no chlorhexidine, single cleansing, multiple cleansing) in Sylhet, Bangladesh. Overall and organism-specific positivity rates were estimated by cord-care regimen and by day of collection. Between September 2008 and October 2009, 1923 infants contributed 5234 umbilical swabs. Positivity rate was high (4057 of 5234, 77.5%) and varied substantially across groups. Immediate (day 1) reductions in cord colonization were observed in single- (prevalence rate ratio = 0.75, 95% confidence interval: 0.70-0.81) and multiple- (prevalence rate ratio = 0.71, 95% confidence interval: 0.66-0.77) cleansing groups. Reductions persisted and increased in magnitude through day 6 only if babies received multiple applications. On days 1, 3, and 6, respectively, multiple cleansing consistently reduced invasive organisms such as Escherichia coli (49%, 64%, and 42% lower), Klebsiella pneumoniae (46%, 53%, and 33% lower), and Staphylococcus aureus (34%, 84%, and 85% lower). Cord cleansing with 4.0% chlorhexidine immediately after birth reduces overall and organism-specific colonization of the stump. Reductions are greater and sustained longer with daily cleansing through the first week of life, suggesting that programs promoting chlorhexidine cleansing should favor multiple over single applications.

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

PubMed

Evans, Malkanthi; Antony, Joseph; Guthrie, Najla; Landes, Bernie; Aruoma, Okezie I

2018-01-01

The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

76 FR 42663 - Magnuson-Stevens Fishery Conservation and Management Act Provisions; Fisheries of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

... through daily Vessel Monitoring System (VMS) catch reports, as is currently proposed through a regulatory..., transfer, receive, sell, purchase, trade, or barter; or attempt to transfer, receive, sell, purchase, trade, or barter, or sell more than 2,000 lb (907 kg) of Atlantic [[Page 42670

27 CFR 25.292 - Daily records of operations.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., or destroyed. (15) Beer received from other breweries or received from pilot brewing plants. (16) Beer and cereal beverage lost due to breakage, theft, casualty, or other unusual cause. (17) Brewing materials sold or transferred to pilot brewing plants (including the name and address of the person to whom...

27 CFR 25.292 - Daily records of operations.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., or destroyed. (15) Beer received from other breweries or received from pilot brewing plants. (16) Beer and cereal beverage lost due to breakage, theft, casualty, or other unusual cause. (17) Brewing materials sold or transferred to pilot brewing plants (including the name and address of the person to whom...

Year-round effects of a four-week randomized controlled trial using different types of feedback on employees' physical activity.

PubMed

Van Hoye, Karen; Wijtzes, Anne I; Lefevre, Johan; De Baere, Stijn; Boen, Filip

2018-04-12

This follow-up study investigated the year-round effects of a four-week randomized controlled trial using different types of feedback on employees' physical activity, including a need-supportive coach intervention. Participants (n = 227) were randomly assigned to a Minimal Intervention Group (MIG; no feedback), a Pedometer Group (PG; feedback on daily steps only), a Display Group (DG; feedback on daily steps, on daily moderate-to-vigorous physical activity [MVPA] and on total energy expenditure [EE]), or a Coaching Group (CoachG; same as DG with need supportive coaching). Daily physical activity level (PAL; Metabolic Equivalent of Task [MET]), number of daily steps, daily minutes of moderate to vigorous physical activity (MVPA), active daily EE (EE > 3 METs) and total daily EE were measured at five time points: before the start of the 4-week intervention, one week after the intervention, and 3, 6, and 12 months after the intervention. For minutes of MVPA, MIG showed higher mean change scores compared with the DG. For steps and daily minutes of MVPA, significantly lower mean change scores emerged for MIG compared with the PG. Participants of the CoachG showed significantly higher change scores in PAL, steps, minutes of MVPA, active EE, total EE compared with the MIG. As hypothesized, participants of the CoachG had significantly higher mean change scores in PAL and total EE compared with groups that only received feedback. However, no significant differences were found for steps, minutes of MVPA and active EE between CoachG and PG. Receiving additional need-supportive coaching resulted in a higher PAL and active EE compared with measurement (display) feedback only. These findings suggest to combine feedback on physical activity with personal coaching in order to facilitate long-term behavioral change. When it comes to increasing steps, minutes of MVPA or active EE, a pedometer constitutes a sufficient tool. Clinical Trails.gov NCT01432327 . Date registered: 12 September 2011.

Volume of hydration in terminal cancer patients.

PubMed

Bruera, E; Belzile, M; Watanabe, S; Fainsinger, R L

1996-03-01

In this retrospective study we reviewed the volume and modality of hydration of consecutive series of terminal cancer patients in two different settings. In a palliative care unit 203/290 admitted patients received subcutaneous hydration for 12 +/- 8 days at a daily volume of 1015 +/- 135 ml/day. At the cancer center, 30 consecutive similar patients received intravenous hydration for 11.5 +/- 5 days (P > 0.2) but at a daily volume of 2080 +/- 720 ml/day (P < 0.001). None of the palliative care unit patients required discontinuation of hydration because of complications. Hypodermoclysis was administered mainly as a continuous infusion, an overnight infusion, or in one to three 1-h boluses in 62 (31%), 98 (48%) and 43 (21%) patients, respectively. Our findings suggest that, in some settings, patients may be receiving excessive volumes of hydration by less comfortable routes such as the intravenous route. Increased education and research in this area are badly needed.

Participation needs of older adults having disabilities and receiving home care: met needs mainly concern daily activities, while unmet needs mostly involve social activities.

PubMed

Turcotte, Pier-Luc; Larivière, Nadine; Desrosiers, Johanne; Voyer, Philippe; Champoux, Nathalie; Carbonneau, Hélène; Carrier, Annie; Levasseur, Mélanie

2015-08-01

Participation is a key determinant of successful aging and enables older adults to stay in their homes and be integrated into the community. Assessing participation needs involves identifying restrictions in the accomplishment of daily and social activities. Although meeting participation needs involves older adults, their caregivers and healthcare providers, little is known about their respective viewpoints. This study thus explored the participation needs of older adults having disabilities as perceived by the older adults themselves, their caregivers and healthcare providers. A qualitative multiple case study consisted of conducting 33 semi-structured interviews in eleven triads, each composed of an older adult, his/her caregiver and a healthcare provider recruited in a Health and Social Services Centre (HSSC) in Québec, Canada. Interview transcripts and reviews of clinical records were analyzed using content analysis and descriptive statistics based on thematic saliency analysis methods. Aged 66 to 88 years, five older adults had physical disabilities, five had mild cognitive impairment and one had psychological problems, leading to moderate to severe functional decline. Caregivers and healthcare providers were mainly women, respectively retired spouses and various professionals with four to 32 years of clinical experience. Participation needs reported by each triad included all domains of participation. Needs related to daily activities, such as personal care, nutrition, and housing, were generally met. Regarding social activities, few needs were met by various resources in the community and were generally limited to personal responsibilities, including making decisions and managing budgets, and some community life activities, such as going shopping. Unmet needs were mainly related to social activities, involving leisure, other community life activities and interpersonal relationships, and some daily activities, including fitness and mobility. This study highlights the complexity of older adults' participation needs, involving daily as well as social activities. Properly assessing and addressing these needs is thus necessary to improve older adults' health and well-being. Discrepancies in the various actors' perceptions of participation needs must be further explored. Additional research would help better understand how to optimize the contribution of community organizations and caregivers.

SU-F-J-69: The Dosimetric Impact of Interfraction Anorectum and Bladder Variability in Prostate Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, V; Chinea, F; Abramowitz, M

Purpose: In the era of dose escalation and numerous protocols evaluating radiation delivery to the prostate, it is imperative to achieve accurate and standardized daily set up. At the Sylvester Comprehensive Cancer Center, patients are instructed to drink 8 ounces of water 30 minutes prior to RT and follow a low residue diet to ensure that the anorectum is not distended and the bladder is adequately filled. If daily CBCT imaging shows any variation, the patient is removed from the table and drinks water or evacuates their rectum prior to a repeat CBCT. Here we attempt to quantify the efficacymore » of this procedure. Methods: CBCTs were collected for 5 patients receiving 40 fractions of definitive treatment for prostate cancer. CBCTs were imported into MIM (v6.5.7, Cleveland OH) and the bladder, anorectum, and prostate were contoured. Using the daily registration reviewed by the attending physician, the planning dose was rigidly transferred to the daily CBCT. On days that multiple CBCTs were performed due to inadequate anorectum or bladder preparation, the repeated and final CBCTs were evaluated for variations in V40Gy and V65Gy to both the anorectum and bladder. Results: A high level of variability in doses to the anorectum and bladder was found in the scans that were not utilized for treatment. The aggregate lower quartile for the unused versus used CBCTs was 27.2% vs. 16.83% for V40Gy and 8.53% vs. 5.66% for V65Gy bladder. The upper quartiles showed to be 48.88% vs. 41.92% and 21.05% vs. 20.55%. The combined lower quartile for the unused vs. used CBCTs was 8.24% vs. 5.49% for V40Gy and 0.57% vs. 0.0% for V65Gy anorectum. The upper quartiles were 34.35% vs. 33.25% and 18.37% vs. 16.11%. Conclusion: This study shows that daily imaging is insufficient and that proper bladder and anorectum preparation are essential to deliver proper treatment.« less

Circadian Clocks for All Meal-Times: Anticipation of 2 Daily Meals in Rats

PubMed Central

Mistlberger, Ralph E.; Kent, Brianne A.; Chan, Sofina; Patton, Danica F.; Weinberg, Alexander; Parfyonov, Maksim

2012-01-01

Anticipation of a daily meal in rats has been conceptualized as a rest-activity rhythm driven by a food-entrained circadian oscillator separate from the pacemaker generating light-dark (LD) entrained rhythms. Rats can also anticipate two daily mealtimes, but whether this involves independently entrained oscillators, one ‘continuously consulted’ clock, cue-dependent non-circadian interval timing or a combination of processes, is unclear. Rats received two daily meals, beginning 3-h (meal 1) and 13-h (meal 2) after lights-on (LD 14∶10). Anticipatory wheel running began 68±8 min prior to meal 1 and 101±9 min prior to meal 2 but neither the duration nor the variability of anticipation bout lengths exhibited the scalar property, a hallmark of interval timing. Meal omission tests in LD and constant dark (DD) did not alter the timing of either bout of anticipation, and anticipation of meal 2 was not altered by a 3-h advance of meal 1. Food anticipatory running in this 2-meal protocol thus does not exhibit properties of interval timing despite the availability of external time cues in LD. Across all days, the two bouts of anticipation were uncorrelated, a result more consistent with two independently entrained oscillators than a single consulted clock. Similar results were obtained for meals scheduled 3-h and 10-h after lights-on, and for a food-bin measure of anticipation. Most rats that showed weak or no anticipation to one or both meals exhibited elevated activity at mealtime during 1 or 2 day food deprivation tests in DD, suggesting covert operation of circadian timing in the absence of anticipatory behavior. A control experiment confirmed that daytime feeding did not shift LD-entrained rhythms, ruling out displaced nocturnal activity as an explanation for daytime activity. The results favor a multiple oscillator basis for 2-meal anticipatory rhythms and provide no evidence for involvement of cue-dependent interval timing. PMID:22355393

Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers.

PubMed

Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

2014-01-01

This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22-48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC(0-24h)), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC(0-24h) were contained within the conventional bioequivalence range of 0.80-1.25 (0.94 [0.88-1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC(0-24h) was not affected. There were no serious adverse events and both formulations were generally well tolerated. At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability.

Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

PubMed Central

Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

2014-01-01

Background This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were generally well tolerated. Conclusion At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability. PMID:24470753

Daily urinary urea excretion to guide intermittent hemodialysis weaning in critically ill patients.

PubMed

Aniort, Julien; Ait Hssain, Ali; Pereira, Bruno; Coupez, Elisabeth; Pioche, Pierre Antoine; Leroy, Christophe; Heng, Anne Elisabeth; Souweine, Bertrand; Lautrette, Alexandre

2016-02-19

There are no easily available markers of renal recovery to guide intermittent hemodialysis (IHD) weaning. The aim of this study was to identify markers for IHD weaning in critically ill patients with acute kidney injury (AKI). We performed a retrospective single-center cohort study of patients treated with IHD for at least 7 days and four dialysis sessions for AKI between 2006 and 2011 in an intensive care unit (ICU) of a French university hospital. Blood and urinary markers were recorded on the day of the last IHD in the ICU for unweaned patients and 2 days after the last IHD for weaned patients. Factors associated with IHD weaning were identified by multiple logistic regression. The areas under the receiver operating characteristic curve (AUROC) and the characteristics of the best diagnostic thresholds were compared. Sixty-seven patients were analyzed, including thirty-seven IHD-weaned patients. Urine output [odds ratio (OR) 1.59, 95% confidence interval (CI) 1.20-2.10 (per ml/kg/24 h increase); P = 0.01] and urinary urea concentration [OR 1.29, 95% CI 1.01-1.64 (per 10 mmol/L increase); P = 0.04] were both associated with IHD weaning. The optimal diagnostic thresholds for IHD weaning were urine output greater than 8.5 ml/kg/24 h, urinary urea concentration greater than 148 mmol/L, and daily urea excretion greater than 1.35 mmol/kg/24 h, with accuracy of 82.1%, 76.1%, and 92.5% (P = 0.03), respectively. The AUROC of daily urinary urea excretion (0.96) was greater than the AUROC of urine output (0.86) or the AUROC of urinary urea concentration (0.83) (P < 0.001). A daily urinary urea excretion greater than 1.35 mmol/kg/24 h was found to be the best marker for weaning ICU patients with AKI from IHD.

Correspondence between Single versus Daily Preference Assessment Outcomes and Reinforcer Efficacy under Progressive-Ratio Schedules

ERIC Educational Resources Information Center

Call, Nathan A.; Trosclair-Lasserre, Nicole M.; Findley, Addie J.; Reavis, Andrea R.; Shillingsburg, M. Alice

2012-01-01

Research has suggested that a daily multiple-stimulus-without-replacement (MSWO) preference assessment may be more sensitive to changes in preference than other assessment formats, thereby resulting in greater correspondence with reinforcer efficacy over time (DeLeon et al., 2001). However, most prior studies have measured reinforcer efficacy…

Mapping daily evapotranspiration at field scales over rainfed and irrigated agricultural areas using remote sensing data fusion

USDA-ARS?s Scientific Manuscript database

A continuous monitoring of daily evapotranspiration (ET) at field scale can be achieved by combining thermal infrared remote sensing data information from multiple satellite platforms. Here, an integrated approach to field scale ET mapping is described, combining multi-scale surface energy balance e...

Brief Daily Writing Activities and Performance on Major Multiple-Choice Exams

ERIC Educational Resources Information Center

Turner, Haley C.; Bliss, Stacy L.; Hautau, Briana; Carroll, Erin; Jaspers, Kathryn E.; Williams, Robert L.

2006-01-01

Although past research indicates that giving brief quizzes, administered either regularly or randomly, may lead to improvement in students' performance on major exams, negligible research has targeted daily writing activities that require the processing of course information at a deeper level than might result from simply reading course materials…

Enhancing the Effectiveness of Special Education Programming for Children with Attention Deficit Hyperactivity Disorder Using a Daily Report Card

ERIC Educational Resources Information Center

Fabiano, Gregory A.; Vujnovic, Rebecca K.; Pelham, William E.; Waschbusch, Daniel A.; Massetti, Greta M.; Pariseau, Meaghan E.; Naylor, Justin; Yu, Jihnhee; Robins, Melissa; Carnefix, Tarah; Greiner, Andrew R.; Volker, Martin

2010-01-01

Children with attention deficit hyperactivity disorder (ADHD) make up a considerable proportion of students who receive special education services in schools. The present study aimed to enhance the outcomes of students with ADHD in special education settings by using a daily report card (DRC). Thirty-three children with ADHD in special education…

Daily Report Card Intervention and Attention Deficit Hyperactivity Disorder: A Meta-Analysis of Single-Case Studies

ERIC Educational Resources Information Center

Pyle, Kellina; Fabiano, Gregory A.

2017-01-01

The daily report card (DRC) is a commonly employed behavioral intervention for treating attention deficit hyperactivity disorder (ADHD) in schools. Much of the support for the DRC comes from single-case studies, which have traditionally received less attention than group studies. This lack of attention to single-case studies results in an…

Daily Report Card Intervention and Attention Deficit Hyperactivity Disorder: A Meta-Analysis of Single-Case Studies

ERIC Educational Resources Information Center

Pyle, Kellina K.; Fabiano, Gregory A.

2017-01-01

The Daily Report Card (DRC) is a commonly employed behavioral intervention for treating Attention Deficit Hyperactivity Disorder (ADHD) in schools. Much of the support for the DRC comes from single-case studies, which have traditionally received less attention than group studies. This lack of attention to single-case studies results in an…

Acute and Chronic Effects of Cocaine on the Spontaneous Behavior of Pigeons

ERIC Educational Resources Information Center

Pinkston, Jonathan W.; Branch, Marc N.

2010-01-01

The present experiment examined the effects of acute and daily cocaine on spontaneous behavior patterns of pigeons. After determining the acute effects of a range of doses, 9 pigeons were divided into three groups that received one of three doses of cocaine daily, either 1.0, 3.0, or 10.0 mg/kg cocaine. Measures were taken of spontaneous…

Does cognitive reappraisal reduce anxiety? A daily diary study of a micro-intervention with individuals with high social anxiety.

PubMed

Kivity, Yogev; Huppert, Jonathan D

2016-03-01

To examine emotion regulation (ER) among individuals with high (HSA) and low social anxiety (LSA) and the effects of 1 week of practiced cognitive reappraisal using self-report, daily diary measures and lab tasks. HSAs received reappraisal (HSA-R; n = 43) or monitoring (HSA-M; n = 40) instructions. LSAs received monitoring instructions (LSA-M; n = 41). Self-report measures of social anxiety and ER, and a lab task of reappraisal were administered at baseline and after 1 week. Daily diaries of anxiety and ER were also collected. At baseline, HSAs compared with LSAs reported lower self-efficacy of reappraisal and higher frequency and self-efficacy of suppression, but no differences emerged in the reappraisal task. Following the intervention, the HSA-R compared with the HSA-M reported lower symptom severity, greater self-efficacy of reappraisal but equal daily anxiety. HSA-R used reappraisal mostly combined with suppression (74.76% of situations). Post hoc analyses demonstrated that clinical diagnosis, but not severity, moderated the intervention effect. The results demonstrate the efficacy of a short intervention in social anxiety, and provide additional areas of research for improving its treatment. (c) 2016 APA, all rights reserved).

Behavioral treatment of caffeinism: reducing excessive coffee drinking.

PubMed Central

Foxx, R M; Rubinoff, A

1979-01-01

Excessive coffee drinking can have deleterious effects because of the large amounts of caffeine that are ingested. Caffeine is thought to be addicting, and prolonged and excessive use can lead to caffeinism, a condition that has serious behavioral and physiological side effects. The present study developed and evaluated a treatment program to reduce excessive daily coffee drinking to moderate and presumably safer levels. Three habitual coffee drinkers received individualized changing criterion programs that systematically and gradually reduced their daily caffeine intake. The coffee drinkers were required to self-monitor and plot their daily intake of caffeine. They received monetary prizes for not exceeding the treatment phase criteria and forfeited a portion of their pretreatment deposit when they did. Their coffee drinking decreased from almost nine cups per day (over 1100 mg of caffeine) during baseline to less than three cups per day (less than 343 mg) at the end of treatment or a reduction of 69%. The treatment effect was maintained during a 10-month follow-up, averaging a 67% reduction from baseline. The program appears to be a reasonable method of reducing and then maintaining daily caffeine intake at less harmful levels. PMID:511802

Comparison of the clinical efficacy of oral terbinafine and ketoconazole combined with cephalexin in the treatment of Malassezia dermatitis in dogs--a pilot study.

PubMed

Rosales, Millie S; Marsella, Rosanna; Kunkle, Gail; Harris, Bradley L; Nicklin, Constance F; Lopez, Jennifer

2005-06-01

The purpose of this randomized, single blinded clinical trial was to evaluate cytologically and clinically the efficacy of oral cephalexin alone and its combination with terbinafine or ketoconazole for the treatment of Malassezia dermatitis in dogs. Twenty-two client-owned dogs with Malassezia dermatitis completed the 3-week study. All received cephalexin (generic, 250 mg or 500 mg) at 22-30 mg kg(-1) twice daily. Eight dogs received terbinafine at 30 mg kg(-1) once daily and seven dogs received ketoconazole (generic, 200 mg) at 5-10 mg kg(-1) twice daily. The remaining seven dogs received cephalexin alone. At week 0 (visit 1) and week 3 (visit 2), mean yeast counts were determined from three affected areas using tape-strip cytology, a clinical index score (CIS) was assigned to the affected areas, and owners evaluated pruritus using a visual analogue scale. All groups showed reduction in mean yeast counts, CIS and pruritus. There was an 86.8%, 80.2% and 28.8% reduction in mean yeast counts from visit 1 to visit 2 for the terbinafine, ketoconazole and cephalexin-only groups, respectively. However, within treatment group comparisons a significant reduction in mean yeast count was only evident for the terbinafine (P < 0.002) and ketoconazole (P < 0.01) groups. Pruritus reduction was only significant for the terbinafine group. These preliminary results suggest that terbinafine should be further assessed for the treatment of canine Malassezia dermatitis.

Inner power, physical strength and existential well-being in daily life: relatives' experiences of receiving soft tissue massage in palliative home care.

PubMed

Cronfalk, Berit Seiger; Strang, Peter; Ternestedt, Britt-Marie

2009-08-01

This article explores relatives' experiences of receiving soft tissue massage as a support supplement while caring for a dying family member at home. In palliative home care, relatives play an important role as carers to seriously ill and dying family members. To improve their quality of life, different support strategies are of importance. Complementary methods, such as soft tissue massage have become an appreciated supplement for these patients. However, only few studies focus on relatives experiences of receiving soft tissue massage as a supplemental support. Qualitative design Nineteen relatives received soft tissue massage (hand or foot) nine times (25 minutes) in their homes. Open-ended semi-structured tape-recorded interviews were conducted once per relative after the nine times of massage, using qualitative content analysis. Soft tissue massage gave the relatives' feelings of 'being cared for', 'body vitality' and 'peace of mind'. For a while, they put worries of daily life aside as they just experienced 'being'. During massage, it became apparent that body and mind is constituted of an indestructible completeness. The overarching theme was 'inner power, physical strength and existential well-being in their daily lives'. All relatives experienced soft tissue massage positively, although they were under considerable stress. Soft tissue massage could be an option to comfort and support relatives in palliative home care. In palliative nursing care, soft tissue massage could present a worthy supplement in supporting caring relatives.

Cognitive evaluation by tasks in a virtual reality environment in multiple sclerosis.

PubMed

Lamargue-Hamel, Delphine; Deloire, Mathilde; Saubusse, Aurore; Ruet, Aurélie; Taillard, Jacques; Philip, Pierre; Brochet, Bruno

2015-12-15

The assessment of cognitive impairment in multiple sclerosis (MS) requires large neuropsychological batteries that assess numerous domains. The relevance of these assessments to daily cognitive functioning is not well established. Cognitive ecological evaluation has not been frequently studied in MS. The aim of this study was to determine the interest of cognitive evaluation in a virtual reality environment in a sample of persons with MS with cognitive deficits. Thirty persons with MS with at least moderate cognitive impairment were assessed with two ecological evaluations, an in-house developed task in a virtual reality environment (Urban DailyCog®) and a divided attention task in a driving simulator. Classical neuropsychological testing was also used. Fifty-two percent of the persons with MS failed the driving simulator task and 80% failed the Urban DailyCog®. Virtual reality assessments are promising in identifying cognitive impairment in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of Sativex(®) on quality of life and activities of daily living in patients with multiple sclerosis spasticity.

PubMed

Arroyo, Rafael; Vila, Carlos; Dechant, Kerry L

2014-07-01

In individuals with multiple sclerosis (MS) spasticity, associated symptoms such as spasms, pain, mobility restrictions and sleep disturbances can interfere with the ability to perform activities of daily living and reduce quality of life (QoL). Recent cross-sectional studies from Europe have confirmed that advancing severity of MS spasticity correlates directly with worsening QoL. The treatment effect of Sativex(®) (GW Pharmaceuticals PLC, Porton Down, UK; Laboratorios Almirall, SA, Barcelona, Spain) on QoL has been evaluated in randomized controlled trials, observational studies conducted under everyday clinical practice conditions and a survey in long-term users. Symptomatic relief of MS spasticity in responders to Sativex was associated with quantifiable improvements in QoL and activities of daily living that were maintained over time. Benefits were perceived by both patients and caregivers.

Fifth-grade children's daily experiences of peer victimization and negative emotions: moderating effects of sex and peer rejection.

PubMed

Morrow, Michael T; Hubbard, Julie A; Barhight, Lydia J; Thomson, Amanda K

2014-10-01

This study examined the relations of fifth-grade children's (181 boys and girls) daily experiences of peer victimization with their daily negative emotions. Children completed daily reports of peer victimization and negative emotions (sadness, anger, embarrassment, and nervousness) on up to eight school days. The daily peer victimization checklist was best represented by five factors: physical victimization, verbal victimization, social manipulation, property attacks, and social rebuff. All five types were associated with increased negative daily emotions, and several types were independently linked to increased daily negative emotions, particularly physical victimization. Girls demonstrated greater emotional reactivity in sadness to social manipulation than did boys, and higher levels of peer rejection were linked to greater emotional reactivity to multiple types of victimization. Sex and peer rejection also interacted, such that greater rejection was a stronger indicator of emotional reactivity to victimization in boys than in girls.

Research and Guidance on Drinking Water Contaminant Mixtures

EPA Science Inventory

Accurate assessment of potential human health risk(s) from multiple-route exposures to multiple chemicals in drinking water is needed because of widespread daily exposure to this complex mixture. Hundreds of chemicals have been identified in drinking water with the mix of chemic...

Air quality and acute deaths in California, 2000-2012.

PubMed

Young, S Stanley; Smith, Richard L; Lopiano, Keneth K

2017-08-01

Many studies have shown an association between air quality and acute deaths, and such associations are widely interpreted as causal. Several factors call causation and even association into question, for example multiple testing and multiple modeling, publication bias and confirmation bias. Many published studies are difficult or impossible to reproduce because of lack of access to confidential data sources. Here we make publically available a dataset containing daily air quality levels, PM 2.5 and ozone, daily temperature levels, minimum and maximum and daily maximum relative humidity levels for the eight most populous California air basins, thirteen years, >2M deaths, over 37,000 exposure days. The data are analyzed using standard time series analysis, and a sensitivity analysis is computed varying model parameters, locations and years. Our analysis finds little evidence for association between air quality and acute deaths. These results are consistent with those for the widely cited NMMAPS dataset when the latter are restricted to California. The daily death variability was mostly explained by time of year or weather variables; Neither PM 2.5 nor ozone added appreciably to the prediction of daily deaths. These results call into question the widespread belief that association between air quality and acute deaths is causal/near-universal. Copyright © 2017 Elsevier Inc. All rights reserved.

Aging Parents' Daily Support Exchanges With Adult Children Suffering Problems.

PubMed

Huo, Meng; Graham, Jamie L; Kim, Kyungmin; Birditt, Kira S; Fingerman, Karen L

2017-06-17

When adult children incur life problems (e.g., divorce, job loss, health problems), aging parents generally report providing more frequent support and experiencing poorer well-being. Yet, it is unclear how adult children's problems may influence aging parents' daily support exchanges with these children or the parents' daily mood. Aging parents from the Family Exchanges Study Wave 2 (N = 207, Mage = 79.86) reported providing and receiving emotional support, practical support, and advice from each adult child each day for 7 days. Parents also rated daily positive and negative mood. Multilevel models showed that aging parents were more likely to provide emotional and practical support to adult children incurring life problems than children not suffering problems. Parents were also more likely to receive emotional support and advice from these children with problems. Further, parents reported less negative mood on days when providing practical support to children with problems. Examining daily support exchanges adds to our understanding of how children's problems influence parent-child ties in late life. Prior research suggests that children's problems upset parents. In this study, however, it appears that supporting adult children who suffer problems may alleviate aging parents' distress regarding such children. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Serum 25-hydroxyvitamin D level is associated with myopia in the Korea national health and nutrition examination survey.

PubMed

Kwon, Jin-Woo; Choi, Jin A; La, Tae Yoon

2016-11-01

The aim of this article was to assess the associations of serum 25-hydroxyvitamin D [25(OH)D] and daily sun exposure time with myopia in Korean adults.This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) of Korean adults in 2010-2012; multiple logistic regression analyses were performed to examine the associations of serum 25(OH)D levels and daily sun exposure time with myopia, defined as spherical equivalent ≤-0.5D, after adjustment for age, sex, household income, body mass index (BMI), exercise, intraocular pressure (IOP), and education level. Also, multiple linear regression analyses were performed to examine the relationship between serum 25(OH)D levels with spherical equivalent after adjustment for daily sun exposure time in addition to the confounding factors above.Between the nonmyopic and myopic groups, spherical equivalent, age, IOP, BMI, waist circumference, education level, household income, and area of residence differed significantly (all P < 0.05). Compared with subjects with daily sun exposure time <2 hour, subjects with sun exposure time ≥2 to <5 hour, and those with sun exposure time ≥5 hour had significantly less myopia (P < 0.001). In addition, compared with subjects were categorized into quartiles of serum 25(OH)D, the higher quartiles had gradually lower prevalences of myopia after adjustment for confounding factors (P < 0.001). In multiple linear regression analyses, spherical equivalent was significantly associated with serum 25(OH)D concentration after adjustment for confounding factors (P = 0.002).Low serum 25(OH)D levels and shorter daily sun exposure time may be independently associated with a high prevalence of myopia in Korean adults. These data suggest a direct role for vitamin D in the development of myopia.

Short-term effects of multiple ozone metrics on daily mortality in a megacity of China.

PubMed

Li, Tiantian; Yan, Meilin; Ma, Wenjun; Ban, Jie; Liu, Tao; Lin, Hualiang; Liu, Zhaorong

2015-06-01

Epidemiological studies have widely demonstrated association between ambient ozone and mortality, though controversy remains, and most of them only use a certain metric to assess ozone levels. However, in China, few studies have investigated the acute effects of ambient ozone, and rare studies have compared health effects of multiple daily metrics of ozone. The present analysis aimed to explore variability of estimated health effects by using multiple temporal ozone metrics. Six metrics of ozone, 1-h maximum, maximum 8-h average, 24-h average, daytime average, nighttime average, and commute average, were used in a time-series study to investigate acute mortality associated with ambient ozone pollution in Guangzhou, China, using 3 years of daily data (2006-2008). We used generalized linear models with Poisson regression incorporating natural spline functions to analyze the mortality, ozone, and covariate data. We also examined the association by season. Daily 1- and 8-h maximum, 24-h average, and daytime average concentrations yielded statistically significant associations with mortality. An interquartile range (IQR) of O3 metric increase of each ozone metric (lag 2) corresponds to 2.92 % (95 % confidence interval (CI) 0.24 to 5.66), 3.60 % (95 % CI, 0.92 to 8.49), 3.03 % (95 % CI, 0.57 to 15.8), and 3.31 % (95 % CI, 0.69 to 10.4) increase in daily non-accidental mortality, respectively. Nighttime and commute metrics were weakly associated with increased mortality rate. The associations between ozone and mortality appeared to be more evident during cool season than in the warm season. Results were robust to adjustment for co-pollutants, weather, and time trend. In conclusion, these results indicated that ozone, as a widespread pollutant, adversely affects mortality in Guangzhou.

Multi-micronutrient-fortified biscuits decreased the prevalence of anaemia and improved iron status, whereas weekly iron supplementation only improved iron status in Vietnamese school children.

PubMed

Hieu, Nguyen Trung; Sandalinas, Fanny; de Sesmaisons, Agnès; Laillou, Arnaud; Tam, Nguyen Phuong; Khan, Nguyen Cong; Bruyeron, Olivier; Wieringa, Frank Tammo; Berger, Jacques

2012-10-28

In Vietnam, nutrition interventions do not target school children despite a high prevalence of micronutrient deficiencies. The present randomised, placebo-controlled study evaluated the impact of providing school children (n 403) with daily multiple micronutrient-fortified biscuits (FB) or a weekly Fe supplement (SUP) on anaemia and Fe deficiency. Micronutrient status was assessed by concentrations of Hb, and plasma ferritin (PF), transferrin receptor (TfR), Zn and retinol. After 6 months of intervention, children receiving FB or SUP had a significantly better Fe status when compared with the control children (C), indicated by higher PF (FB: geometric mean 36·9 (95% CI 28·0, 55·4) μg/l; SUP: geometric mean 46·0 (95% CI 33·0, 71·7) μg/l; C: geometric mean 34·4 (95% CI 15·2, 51·2) μg/l; P < 0·001) and lower TfR concentrations (FB: geometric mean 5·7 (95% CI 4·8, 6·52) mg/l; SUP: geometric mean 5·5 (95% CI 4·9, 6·2) mg/l; C: geometric mean 5·9 (95% CI 5·1, 7·1) mg/l; P = 0·007). Consequently, body Fe was higher in children receiving FB (mean 5·6 (sd 2·2) mg/kg body weight) and SUP (mean 6·1 (sd 2·5) mg/kg body weight) compared with the C group (mean 4·2 (sd 3·3) mg/kg body weight, P < 0·001). However, anaemia prevalence was significantly lower only in the FB group (1·0%) compared with the C group (10·4%, P = 0·006), with the SUP group being intermediate (7·4%). Children receiving FB had better weight-for-height Z-scores after the intervention than children receiving the SUP (P = 0·009). Vitamin A deficiency at baseline modified the intervention effect, with higher Hb concentrations in vitamin A-deficient children receiving FB but not in those receiving the SUP. This indicates that vitamin A deficiency is implicated in the high prevalence of anaemia in Vietnamese school children, and that interventions should take other deficiencies besides Fe into account to improve Hb concentrations. Provision of biscuits fortified with multiple micronutrients is effective in reducing anaemia prevalence in school children.

Antiviral Activity, Safety, and Exposure-Response Relationships of GSK3532795, a Second-Generation Human Immunodeficiency Virus Type 1 Maturation Inhibitor, Administered as Monotherapy or in Combination With Atazanavir With or Without Ritonavir in a Phase 2a Randomized, Dose-Ranging, Controlled Trial (AI468002).

PubMed

Hwang, Carey; Schürmann, Dirk; Sobotha, Christian; Boffito, Marta; Sevinsky, Heather; Ray, Neelanjana; Ravindran, Palanikumar; Xiao, Hong; Keicher, Christian; Hüser, Andreas; Krystal, Mark; Dicker, Ira B; Grasela, Dennis; Lataillade, Max

2017-08-01

GSK3532795 is a second-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor that targets HIV-1 Gag, inhibiting the final protease cleavage between capsid protein p24 and spacer protein-1, producing immature, noninfectious virions. This was a phase 2a, randomized, dose-ranging multipart trial. In part A, subtype B-infected subjects received 5-120 mg GSK3532795 (or placebo) once daily for 10 days. In part B, subtype B-infected subjects received 40 mg or 80 mg GSK3532795 once daily with atazanavir (ATV) with or without (±) ritonavir (RTV) or standard of care (SOC) (tenofovir disoproxil fumarate 300 mg, emtricitabine 200 mg, and ATV/RTV 300 mg/100 mg) for 28 days. In part C, subtype C-infected subjects received 40 mg or 120 mg GSK3532795 once daily (or placebo) for 10 days. Endpoints included change in HIV-1 RNA from baseline on day 11 (parts A/C) or day 29 (part B). A >1 log10 median decline in HIV-1 RNA was achieved by day 11 in parts A and C and day 29 in part B at GSK3532795 doses ≥40 mg; part B subjects receiving GSK3532795 and ATV ± RTV achieved similar declines to those receiving SOC. Median of the maximum declines in HIV-1 RNA were similar for the 40-120 mg once-daily dose groups regardless of baseline Gag polymorphisms. There were no deaths, adverse events leading to discontinuation, or serious adverse events. GSK3532795 demonstrated potent antiviral activity against subtype B (monotherapy or with ATV ± RTV) and subtype C, and was generally well tolerated, which supported continued development of GSK3532795 in subjects with HIV-1 subtype B or subtype C. NCT01803074. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Delamanid for multidrug-resistant pulmonary tuberculosis.

PubMed

Gler, Maria Tarcela; Skripconoka, Vija; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Park, Seung-Kyu; Shim, Tae Sun; Suh, Gee Young; Danilovits, Manfred; Ogata, Hideo; Kurve, Anu; Chang, Joon; Suzuki, Katsuhiro; Tupasi, Thelma; Koh, Won-Jung; Seaworth, Barbara; Geiter, Lawrence J; Wells, Charles D

2012-06-07

Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.).

Breakfast intake among adults with type 2 diabetes: is bigger better?

PubMed Central

Jarvandi, Soghra; Schootman, Mario; Racette, Susan B.

2015-01-01

Objective To assess the association between breakfast energy and total daily energy intake among individuals with type 2 diabetes. Design Cross-sectional study. Daily energy intake was computed from a 24-h dietary recall. Multiple regression models were used to estimate the association between daily energy intake (dependent variable) and quartiles of energy intake at breakfast (independent variable) expressed as either absolute or relative (% of total daily energy intake) terms. Orthogonal polynomial contrasts were used to test for linear and quadratic trends. Models were controlled for sex, age, race/ethnicity, body mass index, physical activity and smoking. In addition, we used separate multiple regression models to test the effect of quartiles of absolute and relative breakfast energy on intake at lunch, dinner, and snacks. Setting The 1999–2004 National Health and Nutrition Examination Survey (NHANES). Subjects Participants aged ≥ 30 years with self-reported history of diabetes (N = 1,146). Results Daily energy intake increased as absolute breakfast energy intake increased (linear trend, P < 0.0001; quadratic trend, P = 0.02), but decreased as relative breakfast energy intake increased (linear trend, P < 0.0001). In addition, while higher quartiles of absolute breakfast intake had no associations with energy intake at subsequent meals, higher quartiles of relative breakfast intake were associated with lower energy intake during all subsequent meals and snacks (P < 0.05). Conclusions Consuming a breakfast that provided less energy or comprised a greater proportion of daily energy intake was associated with lower total daily energy intake in adults with type 2 diabetes. PMID:25529061

A phase I study of recombinant human leukemia inhibitory factor in patients with advanced cancer.

PubMed

Gunawardana, Dishan H; Basser, Russell L; Davis, Ian D; Cebon, Jonathan; Mitchell, Paul; Underhill, Craig; Kilpatrick, Trevor J; Reardon, Katrina; Green, Michael D; Bardy, Peter; Amor, Pene; Crump, David; Ng, Siobhan; Nation, Roger L; Begley, C Glenn

2003-06-01

Leukemia inhibitory factor (LIF) is a pleiotropic molecule of the interleukin 6 family of cytokines. We aimed to examine the safety, pharmacokinetics, and biological effects of recombinant human LIF (rhLIF, emfilermin) in patients with advanced cancer. In stage 1 of the study, 34 patients received rhLIF or placebo (3:1 ratio) at doses of 0.25-16.0 micro g/kg/day or 4.0 micro g/kg three times daily for 7 days. In stage 2, 40 patients received rhLIF or placebo, either once daily for 14 days commencing the day after chemotherapy (0.25-8.0 micro g/kg/day) or for 7 days commencing the day before chemotherapy (4.0 micro g/kg three times daily). The chemotherapy was cisplatin 75 mg/m(2) and paclitaxel 135 mg/m(2). In stage 1, platelet counts increased in most patients, including those who received placebo. Blood progenitor cells increased in response to rhLIF. In stage 2, platelet recovery to baseline levels was earlier for patients receiving higher doses of rhLIF (>/=4.0 micro g/kg/day; P = 0.02). The neutrophil nadir after chemotherapy was less severe in patients receiving >/=4.0 micro g/kg/day of rhLIF. In stages 1 and 2, increases in C reactive protein were seen at higher doses. Several patients developed evidence of autonomic dysfunction, in particular impotence and episodic hypotension. The dose-limiting toxicities were hypotension and rigors. Pharmacokinetic studies demonstrated a short half-life (1-5 h) independent of dose. We demonstrated a biological effect of rhLIF on blood progenitor cells, C reactive protein levels, and hemopoietic recovery after chemotherapy.

Pharmacokinetic profile of extended-release versus immediate-release oral naproxen sodium after single and multiple dosing under fed and fasting conditions: two randomized, open-label trials.

PubMed

Laurora, Irene; Wang, Yuan

2016-10-01

Extended-release (ER) naproxen sodium provides pain relief for up to 24 hours with a single dose (660 mg/day). Its pharmacokinetic profile after single and multiple dosing was compared to immediate release (IR) naproxen sodium in two randomized, open-label, crossover studies, under fasting and fed conditions. Eligible healthy subjects were randomized to ER naproxen sodium 660-mg tablet once daily or IR naproxen sodium 220-mg tablet twice daily (440 mg initially, followed by 220 mg 12 hours later). Primary variables: pharmacokinetic parameters after singleday administration (day 1) and at steady state after multiple-day administration (day 6). Total exposure was comparable for both treatments under fasting and fed conditions. After fasting: peak naproxen concentrations were slightly lower with ER naproxen sodium than with IR naproxen sodium but were reached at a similar time. Fed conditions: mean peak concentrations were comparable but reached after a longer time with ER vs. IR naproxen sodium. ER naproxen sodium was well tolerated, with a similar safety profile to IR naproxen sodium. The total exposure of ER naproxen sodium (660 mg) is comparable to IR naproxen sodium (220 mg) when administered at the maximum over the counter (OTC) dose of 660-mg daily dose on a single day and over multiple days. The rate of absorption is delayed under fed conditions.

Predictors of the transition from experimental to daily smoking among adolescents in the United States.

PubMed

Park, Sunhee; Weaver, Terri E; Romer, Daniel

2009-04-01

This study examined factors affecting the transition from experimental smoking at baseline to two types of daily smoking, temporary daily smoking, and continued daily smoking, at 1-year follow-up. This study analyzed data from the National Longitudinal Study of Adolescent Health (n = 4,903 U.S. adolescents). Baseline predictors were selected based on Problem Behavior Theory. Important problem behavior theory-related predictors of smoking were the number of friends who smoke, academic performance, and alcohol, marijuana, and other illicit drug use. Other significant predictors were age, gender, race, depression, perceived general health, and cigarette availability at home. To prevent teens from progressing to daily smoking, nursing professionals should consider multifaceted factors based on multiple theories.

[A study of non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections in women (the NAPRUTI study)].

PubMed

Beerepoot, M A J; Stobberingh, E E; Geerlings, S E

2006-03-11

Patient enrolment in the 'Non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections' (NAPRUTI) study was started in September 2005. In this study of women with recurrent urinary-tract infections we aim to investigate the effect of 12 months of non-antibiotic prophylaxis in comparison with antibiotic prophylaxis on the rate of recurrence of urinary-tract infections and the development of antibiotic resistance. The study consists of two interlinked, randomised, clinical non-inferiority trials. In one trial, 280 premenopausal women will receive either cranberry capsules (twice daily 500 mg) or standardised antibiotic therapy (once daily 480 mg trimethoprim-sulfamethoxazole). In the other trial, 280 postmenopausal women will receive either oral lactobacilli (twice daily a capsule with > 10(9) colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14) or standardised antibiotic therapy. Non-inferiority of non-antibiotic prophylaxis would be attractive given its potential to reduce the prevalence of microbial resistance to antibiotics significantly.

Improved H-κ Method by Harmonic Analysis on Ps and Crustal Multiples in Receiver Functions with respect to Dipping Moho and Crustal Anisotropy

NASA Astrophysics Data System (ADS)

Li, J.; Song, X.; Wang, P.; Zhu, L.

2017-12-01

The H-κ method (Zhu and Kanamori, 2000) has been widely used to estimate the crustal thickness and Vp/Vs ratio with receiver functions. However, in regions where the crustal structure is complicated, the method may produce uncertain or even unrealistic results, arising particularly from dipping Moho and/or crustal anisotropy. Here, we propose an improved H-κ method, which corrects for these effects first before stacking. The effect of dipping Moho and crustal anisotropy on Ps receiver function has been well studied, but not as much on crustal multiples (PpPs and PpSs+PsPs). Synthetic tests show that the effect of crustal anisotropy on the multiples are similar to Ps, while the effect of dipping Moho on the multiples is 5 times that on Ps (same cosine trend but 5 times in time shift). A Harmonic Analysis (HA) method for dipping/anisotropy was developed by Wang et al. (2017) for crustal Ps receiver functions to extract parameters of dipping Moho and crustal azimuthal anisotropy. In real data, the crustal multiples are much more complicated than the Ps. Therefore, we use the HA method (Wang et al., 2017), but apply separately to Ps and the multiples. It shows that although complicated, the trend of multiples can still be reasonably well represented by the HA. We then perform separate azimuthal corrections for Ps and the multiples and stack to obtain a combined receiver function. Lastly, the traditional H-κ procedure is applied to the stacked receiver function. We apply the improved H-κ method on 40 CNDSN (Chinese National Digital Seismic Network) stations distributed in a variety of geological setting across the Chinese continent. The results show apparent improvement compared to the traditional H-κ method, with clearer traces of multiples and stronger stacking energy in the grid search, as well as more reliable H-κ values.

Food and Nutrient Intake among 12-Month-Old Norwegian-Somali and Norwegian-Iraqi Infants

PubMed Central

Grewal, Navnit Kaur; Andersen, Lene Frost; Kolve, Cathrine Solheim; Kverndalen, Ingrid; Torheim, Liv Elin

2016-01-01

The aim of the present paper was to describe food and nutrient intake among 12-month-old Norwegian-Somali and Norwegian-Iraqi infants, with a focus on iron and vitamin D intake. A cross-sectional survey was conducted from August 2013 through September 2014. Eighty-nine mothers/infants of Somali origin and 77 mothers/infants of Iraqi origin residing in Eastern Norway participated in the study. Data were collected using two 24-h multiple-pass recalls. Forty percent of the Norwegian-Somali infants and 47% of the Norwegian-Iraqi infants were breastfed at 12 months of age (p = 0.414). Median energy percentages (E%) from protein, fat and carbohydrates were within the recommended intake ranges, except the level of saturated fats (12–13 E%). Median intakes of almost all micronutrients were above the recommended daily intakes. Most of the infants consumed iron-enriched products (81%) and received vitamin D supplements (84%). The median intakes of iron and vitamin D were significantly higher among infants receiving iron-enriched products and vitamin D supplements compared to infants not receiving such products (p < 0.001). The findings indicate that the food and nutrient intake of this group of infants in general seems to be in accordance with Norwegian dietary recommendations. Foods rich in iron and vitamin D supplements were important sources of the infants’ intake of iron and vitamin D and should continue to be promoted. PMID:27690092

Factors Related to Premenstrual Syndrome in College Women.

ERIC Educational Resources Information Center

Pierce, Charmaine; Young, Michael

A study sought to determine the incidence of Premenstrual Syndrome (PMS) and identify factors related to PMS among college women. Responses were received from a questionnaire sent to 293 subjects. Questions briefly touched upon life-style (taking the pill, having received a gynecological exam, amount of daily exercise and provided a checklist of…

Evaluation in the Older Blind Independent Living Program: Advantages of a Structural Equation Modeling Approach. Research Report

ERIC Educational Resources Information Center

Giesen, Martin J.; Cavenaugh, Brenda S.

2006-01-01

Rehabilitation Services Administration (RSA) requires that independent living programs annually report demographic information on consumers receiving services and the numbers receiving specific types of services. Although some states collect information on consumer outcomes (for example, improvement in daily living skills), RSA does not request…

Multi-model ensemble hydrologic prediction using Bayesian model averaging

NASA Astrophysics Data System (ADS)

Duan, Qingyun; Ajami, Newsha K.; Gao, Xiaogang; Sorooshian, Soroosh

2007-05-01

Multi-model ensemble strategy is a means to exploit the diversity of skillful predictions from different models. This paper studies the use of Bayesian model averaging (BMA) scheme to develop more skillful and reliable probabilistic hydrologic predictions from multiple competing predictions made by several hydrologic models. BMA is a statistical procedure that infers consensus predictions by weighing individual predictions based on their probabilistic likelihood measures, with the better performing predictions receiving higher weights than the worse performing ones. Furthermore, BMA provides a more reliable description of the total predictive uncertainty than the original ensemble, leading to a sharper and better calibrated probability density function (PDF) for the probabilistic predictions. In this study, a nine-member ensemble of hydrologic predictions was used to test and evaluate the BMA scheme. This ensemble was generated by calibrating three different hydrologic models using three distinct objective functions. These objective functions were chosen in a way that forces the models to capture certain aspects of the hydrograph well (e.g., peaks, mid-flows and low flows). Two sets of numerical experiments were carried out on three test basins in the US to explore the best way of using the BMA scheme. In the first set, a single set of BMA weights was computed to obtain BMA predictions, while the second set employed multiple sets of weights, with distinct sets corresponding to different flow intervals. In both sets, the streamflow values were transformed using Box-Cox transformation to ensure that the probability distribution of the prediction errors is approximately Gaussian. A split sample approach was used to obtain and validate the BMA predictions. The test results showed that BMA scheme has the advantage of generating more skillful and equally reliable probabilistic predictions than original ensemble. The performance of the expected BMA predictions in terms of daily root mean square error (DRMS) and daily absolute mean error (DABS) is generally superior to that of the best individual predictions. Furthermore, the BMA predictions employing multiple sets of weights are generally better than those using single set of weights.

Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis: A Randomized, Placebo-controlled Clinical Trial.

PubMed

Gordon, Glenn L; Zakko, Salam; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ronald; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P; Lichtenstein, Gary R

2016-04-01

To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. Mesalamine is a first-line treatment for induction and maintenance of UC remission. A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)≤2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission.

User's Satisfaction of Multiple Accounting Record System.

PubMed

Chen, M C; Yu, H C

2016-01-01

The study hospital had developed a multiple account recording system that generates the accounting information of the consumed materials based on daily nursing records. A questionnaire survey was delivered to further investigate the impact of the system. Four concepts of the system were investigated. (1) Supportive and time saving; (2) impact on workflows and job satisfactions; (3) ease of use; and (4) overall satisfactions. The system scored 4.03 out of 5 as the highest for helpfulness for daily practices, 3.98 for decrease the time for recording material consumptions, 3.98 for actually changed the way they work. Users mostly expressed positive attitude towards the system.

Effects of rumen-protected choline supplementation on metabolic and performance responses of transition dairy cows.

PubMed

Leiva, T; Cooke, R F; Brandão, A P; Marques, R S; Vasconcelos, J L M

2015-04-01

The objective of this experiment was to compare metabolic and milk production parameters in dairy cows supplemented and nonsupplemented with rumen-protected choline (RPC) during the transition period. Twenty-three nonlactating, multiparous, pregnant Holstein cows were ranked by BW and BCS 21 d before expected date of calving and immediately were assigned to receive (n = 12) or not receive (control; n = 11) RPC until 45 d in milk (DIM). Cows supplemented with RPC received (as-fed basis) 50 and 100 g/d of RPC (18.8% choline) before and after calving, respectively. Before calving, cows were maintained in 2 drylot pens according to treatment with ad libitum access to corn silage, and individually they received (as-fed basis) 3 kg/cow daily of a concentrate. Upon calving, cows were moved to 2 adjacent drylot pens according to treatment, milked twice daily, offered (as-fed basis) 35 kg/cow daily of corn silage, and individually received a concentrate formulated to meet their nutritional requirements after milking. The RPC was individually offered to cows as a topdressing into the morning concentrate feeding. Before calving, cow BW and BCS were recorded weekly, and blood samples were collected every 5 d beginning on d -21 relative to expected calving date. Upon calving and until 45 DIM, BW and BCS were recorded weekly, individual milk production was recorded daily, and milk samples were collected once a week and analyzed for fat, protein, and total solids. Blood samples were collected every other day from 0 to 20 DIM and every 5 d from 20 to 45 DIM. Based on actual calving dates, cows receiving RPC or control began receiving treatments 16.8 ± 1.7 and 17.3 ± 2.0 d before calving, respectively. No treatment effects were detected (P ≥ 0.18) on postpartum concentrate intake, BW and BCS, or serum concentrations of cortisol, β-hydroxybutyrate, NEFA, glucose, and IGF-I. Cows supplemented with RPC had greater (P ≤ 0.01) mean serum haptoglobin and insulin concentrations compared with control. Cows supplemented with RPC had greater (P < 0.01) milk protein, total solids (P < 0.01), and milk fat concentrations (P = 0.09) compared with control. No treatment effects were detected (P ≥ 0.43) for milk yield parameters, such as fat-corrected or solids-corrected milk yield. In conclusion, supplementing RPC to transition dairy cows increased haptoglobin and insulin concentrations and benefited milk composition.

The anti-oxidant effects of ginger and cinnamon on spermatogenesis dys-function of diabetes rats.

PubMed

Khaki, Arash; Khaki, Amir Afshin; Hajhosseini, Laleh; Golzar, Farhad Sadeghpour; Ainehchi, Nava

2014-01-01

Diabetes rats have been linked to reproductive dysfunction and plant medicine has been shown to be effective in its treatment. Antioxidants have distinctive effects on spermatogenesis, sperm biology and oxidative stress, and changes in anti-oxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. Ginger and cinnamon are strong anti-oxidants and have been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. The present study examined the influence of combined ginger and cinnamon on spermatogenesis in STZ-induced diabetes in male Wistar rats. Animals (n = 80) were allocated randomly into eight groups, 10 each: Group 1: Control rats given only 5cc Normal saline (0.9% NaCl) daily;Group2: rats received ginger (100mg/kg/rat) daily; Group 3: rats received cinnamon (75mg/kg) daily; Group 4: rats received ginger and cinnamon, (100mg/kg/rat ginger and 75mg/kg cinnamon) daily; Group 5: Diabetic control rats received only normal saline. Group 6: Diabetic rats received 100mg/kg/day ginger; Group 7: Diabetic rats received 75mg /kg/ day cinnamon; Group 8: Diabetic rats received ginger and cinnamon (100mg/kg/day and 75mg/kg /day). Diabetes was induced with 55 mg/kg, single intra-peritoneal injection of STZ in all groups. At the end of the experiment (56th day), blood samples were taken for determination of testosterone, LH,FSH, total anti-oxidant capacity, and levels of malondialdehyde, SOD, Catalase and GPX. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis. Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased in ginger and cinnamon and combined ginger and cinnamon treated diabetic rats compared with control groups. Serum testosterone, LH and FSH were higher compared to control group and also serum anti-oxidants (TAC, SOD, GPX and catalase) all were increased at the end of treatment. Combined ginger and cinnamon showed more intense increase in all parameters compare to ginger and cinnamon alone. Most of the results were significant (P<0.05). We concluded that combined ginger and cinnamon have significant beneficial effects on the sperm viability, motility, and serum total testosterone, LH,FSH and serum anti-oxidants' level and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetics.

Forecasting daily patient volumes in the emergency department.

PubMed

Jones, Spencer S; Thomas, Alun; Evans, R Scott; Welch, Shari J; Haug, Peter J; Snow, Gregory L

2008-02-01

Shifts in the supply of and demand for emergency department (ED) resources make the efficient allocation of ED resources increasingly important. Forecasting is a vital activity that guides decision-making in many areas of economic, industrial, and scientific planning, but has gained little traction in the health care industry. There are few studies that explore the use of forecasting methods to predict patient volumes in the ED. The goals of this study are to explore and evaluate the use of several statistical forecasting methods to predict daily ED patient volumes at three diverse hospital EDs and to compare the accuracy of these methods to the accuracy of a previously proposed forecasting method. Daily patient arrivals at three hospital EDs were collected for the period January 1, 2005, through March 31, 2007. The authors evaluated the use of seasonal autoregressive integrated moving average, time series regression, exponential smoothing, and artificial neural network models to forecast daily patient volumes at each facility. Forecasts were made for horizons ranging from 1 to 30 days in advance. The forecast accuracy achieved by the various forecasting methods was compared to the forecast accuracy achieved when using a benchmark forecasting method already available in the emergency medicine literature. All time series methods considered in this analysis provided improved in-sample model goodness of fit. However, post-sample analysis revealed that time series regression models that augment linear regression models by accounting for serial autocorrelation offered only small improvements in terms of post-sample forecast accuracy, relative to multiple linear regression models, while seasonal autoregressive integrated moving average, exponential smoothing, and artificial neural network forecasting models did not provide consistently accurate forecasts of daily ED volumes. This study confirms the widely held belief that daily demand for ED services is characterized by seasonal and weekly patterns. The authors compared several time series forecasting methods to a benchmark multiple linear regression model. The results suggest that the existing methodology proposed in the literature, multiple linear regression based on calendar variables, is a reasonable approach to forecasting daily patient volumes in the ED. However, the authors conclude that regression-based models that incorporate calendar variables, account for site-specific special-day effects, and allow for residual autocorrelation provide a more appropriate, informative, and consistently accurate approach to forecasting daily ED patient volumes.

Empowering Marginalized Youth: Curriculum, Media Studies, and Character Development

ERIC Educational Resources Information Center

Ng-A-Fook, Nicholas; Radford, Linda; Yazdanian, Shenin; Norris, Tracy

2013-01-01

Students are bombarded daily with print, visual, and digital media. Whether it is on a billboard, listening to an iPod on the way to school, or text messaging a friend during class, youth culture is hardwired into these multiple forms of communication technologies. Nonetheless, the daily life and respective experiences of students are often still…

Examining the Influence of a Mobile Learning Intervention on Third Grade Math Achievement

ERIC Educational Resources Information Center

Kiger, Derick; Herro, Dani; Prunty, Deb

2012-01-01

Third grade students at a Midwestern elementary school participated in a 9-week mobile learning intervention (MLI). Two classrooms used Everyday Math and daily practice using flashcards, etc., to learn multiplication. Two other classrooms used Everyday Math and web applications for the iPod touch for daily practice. MLI students outperformed…

Formative Assessment Using Direct Behavior Ratings: Evaluating Intervention Effects of Daily Behavior Report Cards

ERIC Educational Resources Information Center

Sims, Wesley A.; Riley-Tillman, Chris; Cohen, Daniel R.

2017-01-01

This study examined the treatment sensitivity of "Direct Behavior Rating-Single Item Scales" (DBR-SIS) in response to an evidence-based intervention delivered in a single-case, multiple-baseline design. DBR-SIS was used as a formative assessment in conjunction with a frequently used intervention in schools, a Daily Behavior Report Card…

21 CFR 320.31 - Applicability of requirements regarding an “Investigational New Drug Application.”

Code of Federal Regulations, 2010 CFR

2010-04-01

... patients where either the maximum single or total daily dose exceeds that specified in the labeling of the... application. (2) A multiple-dose study in normal subjects or patients where either the single or total daily... conducting the study, including any contract research organization, shall retain reserve samples of any test...

The Effectiveness of SpeechEasy during Situations of Daily Living

ERIC Educational Resources Information Center

O'Donnell, Jennifer J.; Armson, Joy; Kiefte, Michael

2008-01-01

A multiple single-subject design was used to examine the effects of SpeechEasy on stuttering frequency in the laboratory and in longitudinal samples of speech produced in situations of daily living (SDL). Seven adults who stutter participated, all of whom had exhibited at least 30% reduction in stuttering frequency while using SpeechEasy during…

From conventionally fractionated radiation therapy to hyperfractionated radiation therapy alone and with concurrent chemotherapy in patients with early-stage nonsmall cell lung cancer.

PubMed

Jeremić, Branislav; Milicić, Biljana

2008-02-15

The authors' single-institution experience in patients with early-stage (I and II) nonsmall cell lung cancer (NSCLC) who were treated between 1980 and 1998 with either conventionally fractionated (CF) radiation therapy (RT), or hyperfractionated (HFX) RT, or HFX RT with concurrent paclitaxel/carboplatin (HFX RT-Pac/C) was reviewed. Seventy-eight patients received 60 grays (Gy) in 30 daily fractions (CF), 116 patients received 69.6 Gy (1.2 Gy twice daily), and 56 patients received 67.6 Gy (1.3 Gy twice daily) with concurrent, low-dose, daily C (25 mg/m2) and Pac (10 mg/m2). Biologically equivalent doses for the 3 groups were 72 Gy, 78 Gy, and 76 Gy, respectively, for acute effects (alpha/beta = 10 Gy) and 120 Gy, 111 Gy, and 111 Gy, respectively, for late effects (alpha/beta = 2 Gy). For all 250 patients, the overall median survival was 27 months, the cause-specific survival was 27 months, the local progression-free survival was 32 months, and distant metastasis-free survival was not achieved; and the respective 5-year survival rates were 27%, 32%, 45%, and 68%. CF achieved significantly inferior survival than either HFX RT alone or HFX RT-Pac/C (P = .0332 and P = .0013, respectively), and no difference was observed between the 2 HFX RT regimens (P = .1934). Only acute hematologic high-grade toxicity (grade >or=3) was more frequent with HFX RT-Pac/C than with either RT alone, whereas other toxicities were similar between the 3 treatment groups. HFX RT with or without concurrent chemotherapy may be better than CF in patients with early-stage NSCLC. The role of chemotherapy deserves further investigation, because the group that received chemotherapy in the current study had a higher incidence of acute high-grade hematologic toxicity. Cancer 2008. (c) 2008 American Cancer Society.

Clinical Value of CYP2C19 Genetic Testing for Guiding the Antiplatelet Therapy in a Chinese Population.

PubMed

Shen, De-Liang; Wang, Bo; Bai, Jing; Han, Qing; Liu, Chuang; Huang, Xiao-Hui; Zhang, Jin-Ying

2016-03-01

To compare the clinical effects between individual antiplatelet therapy guided by CYP2C19 genetic testing and conventional dual antiplatelet therapy in patients with coronary artery disease after percutaneous coronary intervention. In total of 628 coronary artery disease patients who had undergone successful percutaneous coronary intervention were included in this study. Patients were consecutively divided into routine group (n = 319) and individual group (n = 309) because of weather received CYP2C19 genetic testing. The individual group was divided again into extensive metabolizer group, intermediate metabolizer group, and poor metabolizer group according to CYP2C19 genotype. Then extensive metabolizer group received 75 mg daily of clopidogrel, intermediate metabolizer group received 150 mg daily of clopidogrel, and poor metabolizer group received ticagrelor 90 mg twice daily. Routine group was treated with clopidogrel 75 mg daily conventionally. The primary end points were defined as major adverse cardiovascular events (MACE), namely a composite of death from any cause, myocardial infarction, or target vessel revascularization. Safety end points were bleeding events classified by GUSTO. All the 628 patients were followed for an average of 12 months and clinical outcomes were analyzed at 1, 6, and 12 months after discharge. The morbidity rates of MACE in individual group were all lower than those in routine group at 1, 6, and 12 months (1.3% vs. 5.6%, P = 0.003; 3.2% vs. 7.8%, P = 0.012; 4.2% vs. 9.4%, P = 0.010). No significant difference in the rates of bleeding was found between the 2 groups (P > 0.05). Even performed a multivariate logistic regression analysis, the benefit of individual antiplatelet therapy remained. Individual antiplatelet therapy guided by CYP2C19 genetic testing significantly reduced the rate of MACE without an increase in the rate of bleeding in the near term in this Chinese population.

Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia.

PubMed

Gliozzi, Micaela; Walker, Ross; Muscoli, Saverio; Vitale, Cristiana; Gratteri, Santo; Carresi, Cristina; Musolino, Vincenzo; Russo, Vanessa; Janda, Elzbieta; Ragusa, Salvatore; Aloe, Antonio; Palma, Ernesto; Muscoli, Carolina; Romeo, Franco; Mollace, Vincenzo

2013-12-10

Statins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders, some patients experience statin-induced side effects. We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values. The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia. A prospective, open-label, parallel group, placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was designed. Patients were randomly assigned to a control group receiving placebo (n=15), two groups receiving orally administered rosuvastatin (10 and 20mg/daily for 30 days; n=16 for each group), a group receiving BPF alone orally (1000 mg/daily for 30 days; n=15) and a group receiving BPF (1000 mg/daily given orally) plus rosuvastatin (10mg/daily for 30 days; n=15). Both doses of rosuvastatin and BPF reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients, compared to control group. The cholesterol lowering effect was accompanied by reductions of malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB, which are all biomarkers of oxidative vascular damage, in peripheral polymorphonuclear cells. Addition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone. This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage, suggesting a multi-action enhanced potential for BPF in patients on statin therapy. © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Pharmacological doses of daily ascorbate protect tumors from radiation damage after a single dose of radiation in an intracranial mouse glioma model.

PubMed

Grasso, Carole; Fabre, Marie-Sophie; Collis, Sarah V; Castro, M Leticia; Field, Cameron S; Schleich, Nanette; McConnell, Melanie J; Herst, Patries M

2014-01-01

Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumor environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionizing radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumor, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitizing GBM cells will improve survival of GBM patients. Here, we demonstrate that a single fraction (6 Gy) of radiation combined with a 1 h exposure to ascorbate (5 mM) sensitized murine glioma GL261 cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy) of whole brain radiation combined with daily intraperitoneal injections of ascorbate (1 mg/kg) in an intracranial GL261 glioma mouse model. Tumor-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain 8 days after tumor implantation, a second group received daily intraperitoneal injections of ascorbate (day 8-45) after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumor progression, intraperitoneal ascorbate alone had no effect on tumor progression. Tumor progression was faster in tumor-bearing mice treated with radiation and daily ascorbate than in those treated with radiation alone. Histological analysis showed less necrosis in tumors treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumor microenvironment, which determines whether ascorbate remains outside the cell, acting as a pro-oxidant, or whether it enters the cells and acts as an anti-oxidant.

Training response inhibition to food is associated with weight loss and reduced energy intake

PubMed Central

Lawrence, Natalia S.; O'Sullivan, Jamie; Parslow, David; Javaid, Mahmood; Adams, Rachel C.; Chambers, Christopher D.; Kos, Katarina; Verbruggen, Frederick

2015-01-01

The majority of adults in the UK and US are overweight or obese due to multiple factors including excess energy intake. Training people to inhibit simple motor responses (key presses) to high-energy density food pictures reduces intake in laboratory studies. We examined whether online response inhibition training reduced real-world food consumption and weight in a community sample of adults who were predominantly overweight or obese (N = 83). Participants were allocated in a randomised, double-blind design to receive four 10-min sessions of either active or control go/no-go training in which either high-energy density snack foods (active) or non-food stimuli (control) were associated with no-go signals. Participants' weight, energy intake (calculated from 24-h food diaries), daily snacking frequency and subjective food evaluations were measured for one week pre- and post-intervention. Participants also provided self-reported weight and monthly snacking frequency at pre-intervention screening, and one month and six months after completing the study. Participants in the active relative to control condition showed significant weight loss, reductions in daily energy intake and a reduction in rated liking of high-energy density (no-go) foods from the pre-to post-intervention week. There were no changes in self-reported daily snacking frequency. At longer-term follow-up, the active group showed significant reductions in self-reported weight at six months, whilst both groups reported significantly less snacking at one- and six-months. Excellent rates of adherence (97%) and positive feedback about the training suggest that this intervention is acceptable and has the potential to improve public health by reducing energy intake and overweight. PMID:26122756

Healthy Aging 5 Years After a Period of Daily Supplementation With Antioxidant Nutrients: A Post Hoc Analysis of the French Randomized Trial SU.VI.MAX.

PubMed

Assmann, Karen E; Andreeva, Valentina A; Jeandel, Claude; Hercberg, Serge; Galan, Pilar; Kesse-Guyot, Emmanuelle

2015-10-15

This study's objective was to investigate healthy aging in older French adults 5 years after a period of daily nutritional-dose supplementation with antioxidant nutrients. The study was based on the double-blind, randomized trial, Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) Study (1994-2002) and the SU.VI.MAX 2 Follow-up Study (2007-2009). During 1994-2002, participants received a daily combination of vitamin C (120 mg), β-carotene (6 mg), vitamin E (30 mg), selenium (100 µg), and zinc (20 mg) or placebo. Healthy aging was assessed in 2007-2009 by using multiple criteria, including the absence of major chronic disease and good physical and cognitive functioning. Data from a subsample of the SU.VI.MAX 2 cohort, initially free of major chronic disease, with a mean age of 65.3 years in 2007-2009 (n = 3,966), were used to calculate relative risks. Supplementation was associated with a greater healthy aging probability among men (relative risk = 1.16, 95% confidence interval: 1.04, 1.29) but not among women (relative risk = 0.98, 95% confidence interval: 0.86, 1.11) or all participants (relative risk = 1.07, 95% confidence interval: 0.99, 1.16). Moreover, exploratory subgroup analyses indicated effect modification by initial serum concentrations of zinc and vitamin C. In conclusion, an adequate supply of antioxidant nutrients (equivalent to quantities provided by a balanced diet rich in fruits and vegetables) may have a beneficial role for healthy aging. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A 4-Week Intervention Involving Mobile-Based Daily 6-Minute Micro-Sessions of Functional High-Intensity Circuit Training Improves Strength and Quality of Life, but Not Cardio-Respiratory Fitness of Young Untrained Adults.

PubMed

Sperlich, Billy; Hahn, Lea-Sofie; Edel, Antonia; Behr, Tino; Helmprobst, Julian; Leppich, Robert; Wallmann-Sperlich, Birgit; Holmberg, Hans-Christer

2018-01-01

The present study was designed to assess the psycho-physiological responses of physically untrained individuals to mobile-based multi-stimulating, circuit-like, multiple-joint conditioning (Circuit HIIT ) performed either once (1xCircuit HIIT ) or twice (2xCircuit HIIT ) daily for 4 weeks. In this single-center, two-arm randomized, controlled study, 24 men and women (age: 25 ± 5 years) first received no training instructions for 4 weeks and then performed 4 weeks of either 1xCircuit HIIT or 2xCircuit HIIT (5 men and 7 women in each group) daily. The 1xCircuit HIIT and 2xCircuit HIIT participants carried out 90.7 and 85.7% of all planned training sessions, respectively, with average heart rates during the 6-min sessions of 74.3 and 70.8% of maximal heart rate. Body, fat and fat-free mass, and metabolic rate at rest did not differ between the groups or between time-points of measurement. Heart rate while running at 6 km⋅h -1 declined after the intervention in both groups. Submaximal and peak oxygen uptake, the respiratory exchange ratio and heart rate recovery were not altered by either intervention. The maximal numbers of push-ups, leg-levers, burpees, 45°-one-legged squats and 30-s skipping, as well as perception of general health improved in both groups. Our 1xCircuit HIIT or 2xCircuit HIIT interventions improved certain parameters of functional strength and certain dimensions of quality of life in young untrained individuals. However, they were not sufficient to enhance cardio-respiratory fitness, in particular peak oxygen uptake.

Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome.

PubMed

Cataldo, Nicholas A; Barnhart, Huiman X; Legro, Richard S; Myers, Evan R; Schlaff, William D; Carr, Bruce R; Diamond, Michael P; Carson, Sandra A; Steinkampf, Michael P; Coutifaris, Christos; McGovern, Peter G; Gosman, Gabriella; Nestler, John E; Giudice, Linda C

2008-08-01

When used for ovulation induction, higher doses of clomiphene may lead to antiestrogenic side effects that reduce fecundity. It has been suggested that metformin in combination with clomiphene can restore ovulation to some clomiphene-resistant anovulators with polycystic ovary syndrome (PCOS). Our objective was to determine if cotreatment with extended-release metformin (metformin XR) can lower the threshold dose of clomiphene needed to induce ovulation in women with PCOS. A secondary analysis of data from the National Institute of Child Health and Human Development Cooperative Multicenter Reproductive Medicine Network prospective, double-blind, placebo-controlled multicenter clinical trial, Pregnancy in Polycystic Ovary Syndrome, was performed. Study volunteers at multiple academic medical centers were included. Women with PCOS and elevated serum testosterone who were randomized to clomiphene alone or with metformin (n = 209 in each group) were included in the study. Clomiphene citrate, 50 mg daily for 5 d, was increased to 100 and 150 mg in subsequent cycles if ovulation was not achieved; half also received metformin XR, 1000 mg twice daily. Treatment was for up to 30 wk or six cycles, or until first pregnancy. Ovulation was confirmed by a serum progesterone more than or equal to 5 ng/ml, drawn prospectively every 1-2 wk. The overall prevalence of at least one ovulation after clomiphene was 75 and 83% (P = 0.04) for the clomiphene-only and clomiphene plus metformin groups, respectively. Using available data from 314 ovulators, the frequency distribution of the lowest clomiphene dose (50, 100, or 150 mg daily) resulting in ovulation was indistinguishable between the two treatment groups. Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.

A review of OROS methylphenidate (Concerta(®)) in the treatment of attention-deficit/hyperactivity disorder.

PubMed

Katzman, Martin A; Sternat, Tia

2014-11-01

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural disorder with onset during childhood. It affects a child's development, both at home and at school, and impacts on social, emotional and cognitive functioning, in both the home and the school environment. Untreated ADHD is very often associated with poor academic achievement, low occupational status, increased risk of substance abuse and delinquency. Current practice guidelines recommend a multimodal approach in the treatment of ADHD, which includes educational, behavioural and mental health interventions, and pharmacological management. Stimulant medications, including methylphenidate (MPH) and amphetamine products, are recommended as first-line pharmacotherapy in the treatment of ADHD. The choice of stimulant is influenced by several factors; the most influential factor is the duration of action. Long-acting medication provides benefits long after school and work. It also increases the likelihood of once-daily dosing, thereby eliminating the need for mid-day dosing, making the treatment more private, avoiding stigma and improving adherence to medication. MPH is the most widely used psychotropic medication in child psychiatry. It was first developed for use in children as an oral, immediate-release formulation and more recently as various extended-release formulations. These latter formulations include the 12 h preparation Concerta(®) (osmotic-release oral system [OROS] MPH), which utilizes an osmotic pump system, designed to overcome the difficulties of multiple daily dosing. Since it received approval from the US Food and Drug Administration in August 2000, OROS MPH has been quickly and widely accepted as one of the preferred treatments for ADHD because of its once-daily dosing. This paper reviews the data in support of long-acting OROS MPH in children, adolescents and adults, both in ADHD and in association with its comorbidities.

A multi-sensor monitoring system of human physiology and daily activities.

PubMed

Doherty, Sean T; Oh, Paul

2012-04-01

To present the design and pilot test results of a continuous multi-sensor monitoring system of real-world physiological conditions and daily life (activities, travel, exercise, and food consumption), culminating in a Web-based graphical decision-support interface. The system includes a set of wearable sensors wirelessly connected to a "smartphone" with a continuously running software application that compresses and transmits the data to a central server. Sensors include a Global Positioning System (GPS) receiver, electrocardiogram (ECG), three-axis accelerometer, and continuous blood glucose monitor. A food/medicine diary and prompted recall activity diary were also used. The pilot test involved 40 type 2 diabetic patients monitored over a 72-h period. All but three subjects were successfully monitored for the full study period. Smartphones proved to be an effective hub for managing multiple streams of data but required attention to data compression and battery consumption issues. ECG, accelerometer, and blood glucose devices performed adequately as long as subjects wore them. GPS tracking for a full day was feasible, although significant efforts are needed to impute missing data. Activity detection algorithms were successful in identifying activities and trip modes but could benefit by incorporating accelerometer data. The prompted recall diary was an effective tool for augmenting algorithm results, although subjects reported some difficulties with it. The food and medicine diary was completed fully, although end times and medicine dosages were occasionally missing. The unique combination of sensors holds promise for increasing accuracy and reducing burden associated with collecting individual-level activity and physiological data under real-world conditions, but significant data processing issues remain. Such data will provide new opportunities to explore the impacts of human geography and daily lifestyle on health at a fine spatial/temporal scale.

Alterations in taste perception due to recreational drug use are due to smoking a substance rather than ingesting it.

PubMed

Dovey, Terence M; Boyland, Emma J; Trayner, Penelope; Miller, Jo; Rarmoul-Bouhadjar, Amin; Cole, Jon; Halford, Jason C G

2016-12-01

Two studies explored the differences in tastant (salt, sour, bitter, sweet and spicy) concentration preference between recreational drug users and abstainers. In study 1, 250 opportunistically recruited abstainers, cannabis only users and multiple-drug users completed psychometric questionnaires and a concentration preference tastant test. In study 2, 76 participants purposefully recruited abstainers, daily tobacco users, recreational cannabis users and daily cannabis users completed the same protocol as study 1. Study 1 demonstrated that both multiple drug users and cannabis users had a higher preference for salt and sour tastants than abstainers. Study 2 showed that daily cannabis and tobacco users had a higher preference for sweet and spicy tastants than recreational cannabis users and abstainers. As predicted, recreational drug users scored higher on both sensation-seeking and impulsivity compared to abstainers. Participants who habitually smoke tobacco or cannabis daily have different concentration preference for specific tastants. The aim of the current study was to provide an explanation for the inconsistency in published results on taste preferences in recreational drug users. The data offered in this paper indicate that variation in recruitment strategy, definition of 'drug users', and mode of drug delivery, as well as multiple drug use, may explain the preference for stronger tastants in habitual drug users. Future research exploring the psychobiological underpinnings of the impact of drug use on food preferences should carefully define recreational drug user groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medical resource utilization among community-acquired pneumonia patients initially treated with levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily: a US-based study.

PubMed

Frei, C R; Jaso, T C; Mortensen, E M; Restrepo, M I; Raut, M K; Oramasionwu, C U; Ruiz, A D; Makos, B R; Ruiz, J L; Attridge, R T; Mody, S H; Fisher, A; Schein, J R

2009-04-01

The 2007 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend that community-acquired pneumonia (CAP) patients admitted to hospital wards initially receive respiratory fluoroquinolone monotherapy or beta-lactam plus macrolide combination therapy. There is little evidence as to which regimen is preferred, or if differences in medical resource utilization exist between therapies. Thus, the authors compared length of hospital stay (LOS) and length of intravenous antibiotic therapy (LOIV) for patients who received initial levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily ('combination therapy'). Adult hospital CAP cases from January 2005 to December 2007 were identified by principal discharge diagnosis code. Patients with a chest infiltrate and medical notes indicative of CAP were included. Direct intensive care unit admits and healthcare-associated cases were excluded. A propensity score technique was used to balance characteristics associated with initial antimicrobial therapy using multivariable regression to derive the scores. Propensity score categories, defined as propensity score quintiles, rather than propensity scores themselves, were used in the least squares regression model to assess the impact of LOS and LOIV. A total of 495 patients from six hospitals met study criteria. Of these, 313 (63%) received levofloxacin and 182 (37%) received combination therapy. Groups were similar with respect to age, sex, most comorbidities, presenting signs and symptoms, and Pneumonia Severity Index (PSI) risk class. Patients on combination therapy were more likely to have heart failure and receive pre-admission antibiotics. Adjusted least squares mean (+/-SE) LOS and LOIV were shorter with levofloxacin versus combination therapy: LOS, 4.6 +/- 0.17 vs. 5.4 +/- 0.22 days, p < 0.01; and LOIV, 3.6 +/- 0.17 vs. 4.8 +/- 0.21 days, p < 0.01. Results for PSI risk class III or IV patients were: LOS, 5.0 +/- 0.30 vs. 5.9 +/- 0.37 days, p = 0.07; and LOIV, 3.7 +/- 0.33 vs. 5.2 +/- 0.39 days, p < 0.01. Due to the retrospective study design, limited sample size, and scope (single health-network), the authors encourage replication of this study in other data sources. Given the LOS and LOIV reductions of 0.8 and 1.2 days, respectively, utilization of levofloxacin 750 mg daily for CAP patients admitted to the medical floor has the potential to result in substantial cost savings for US hospitals.

Betamethasone enemata in ulcerative colitis

PubMed Central

Matts, S. G. Flavell

1962-01-01

In this series a very large therapeutic dose of corticosteroid was administered by retention enemata. For the first week the author gave the equivalent of between 300 and 750 mg. of cortisone daily and for the next three weeks 150 to 375 mg. daily. The results were excellent but systemic effects were noted in all who received more than the smallest dose used. ImagesFIG. 1FIG. 2 PMID:13933911

Activation of the DLPFC Reveals an Asymmetric Effect in Risky Decision Making: Evidence from a tDCS Study

PubMed Central

Huang, Daqiang; Chen, Shu; Wang, Siqi; Shi, Jinchuan; Ye, Hang; Luo, Jun; Zheng, Haoli

2017-01-01

The phenomenon of loss aversion (the tendency for losses to have a greater impact than comparable gains) has long been observed in daily life. Neurocognitive studies and brain imaging studies have shed light on the correlation between the phenomenon of loss aversion and the brain region of the prefrontal cortex. Recent brain stimulation studies using bilateral transcranial magnetic stimulation or transcranial direct current stimulation (tDCS) have obtained various results showing the causal relationship between brain regions and decision making. With the goal of studying whether unilateral stimulation can change participants’ risky decision making in the frames of gains and losses, we applied different polarities of tDCS over the regions of the right or left prefrontal cortex. We also designed a risk measurement table (Multiple Price List) to reflect the participants’ attitudes toward risky decision making via the crossover point including the frames of gains and losses. The results of our experiment indicated that the participants tended to be more risk averse in the gain frame after receiving left anodal tDCS and more risk seeking in the loss frame after receiving right cathodal tDCS, which was consistent with the hypothesis that the process of risky decision making was correlated with the interaction of multiple systems in the brain. Our conclusion revealed an asymmetric effect of right/left DLPFC when the participants faced gains and losses, which partially provided the neural evidence and a feasible paradigm to help better understand risky decision making and loss aversion. The current study can not only expand the traditional understanding of the behavioral preferences of humans in economics but also accommodate empirical observations of behavioral economists on the preferences of humans. PMID:28174549

Automatic online adaptive radiation therapy techniques for targets with significant shape change: a feasibility study.

PubMed

Court, Laurence E; Tishler, Roy B; Petit, Joshua; Cormack, Robert; Chin, Lee

2006-05-21

This work looks at the feasibility of an online adaptive radiation therapy concept that would detect the daily position and shape of the patient, and would then correct the daily treatment to account for any changes compared with planning position. In particular, it looks at the possibility of developing algorithms to correct for large complicated shape change. For co-planar beams, the dose in an axial plane is approximately associated with the positions of a single multi-leaf collimator (MLC) pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping monitor units (MUs) and number of segments constant for a given beam (fluences are different). Bulk registration (3D) of planning and daily CT images gives global shifts. Slice-by-slice (2D) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beam's-eye-view calculation to account for local linear shifts. A planning study was carried out using two head and neck region MR images of a healthy volunteer which were contoured to simulate a base-of-tongue treatment: one with the head straight (used to simulate the planning image) and the other with the head tilted to the left (the daily image). Head and neck treatment was chosen to evaluate this technique because of its challenging nature, with varying internal and external contours, and multiple degrees of freedom. Shape change was significant: on a slice-by-slice basis, local rotations in the daily image varied from 2 to 31 degrees, and local shifts ranged from -0.2 to 0.5 cm and -0.4 to 0.0 cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave reasonable target coverage (100%, 90% and 80% of the base-of-tongue, left nodes and right nodes, respectively, receiving the daily prescription dose), and kept the daily cord dose below the limit used in the original plan (65%, equivalent to 46 Gy over 35 fractions). Most of the loss of coverage was due to one shoulder being raised more superior relative to the other shoulder compared with the plan. This type of skew-like motion is not accounted for by the proposed ART technique. In conclusion, this technique has potential to correct for fairly extreme daily changes in patient setup, but some control of the daily position would still be necessary. Importantly, it was possible to combine treatments from different plans (MLC sequences) to correct for position and shape change.

Case Study: The Use of Massage Therapy to Relieve Chronic Low-Back Pain.

PubMed

Allen, Laura

2016-09-01

To study the effects of massage on chronic low-back pain in a patient with four different diagnoses: osteoarthritis, scoliosis, spinal stenosis, and degenerative disc disease. The patient's goal was to cut down on the amount of pain medication he takes. A 63-year-old man with chronic back pain received four massages across a twenty-day period. Progress was recorded using the Oswestry Low Back Pain Scale, as he self-reported on levels of pain and interference with his activities of daily living. Improvement was noted in 9 out of 10 measurements of self-reported pain and activities of daily living, with the only exception being his ability to lift heavy objects, which remained unchanged. The most dramatic differences were improvements in his ability to walk, and in the changing degrees of pain. The client also self-reported being able to decrease his pain medication and the ability to ride his bicycle for the first time in years. Massage therapy is a promising treatment for chronic low-back pain for patients who may have multiple pathologies, any one of which could be responsible for the condition. Further study is encouraged to determine the efficacy of massage therapy as a readily accessible, lower-cost alternative to more invasive therapies and as an adjunct to regular medical care, when appropriate.

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination.

PubMed

El Hachem, Hady; Antaki, Roland; Sylvestre, Camille; Kadoch, Isaac-Jacques; Lapensée, Louise; Bouet, Pierre Emmanuel

2017-01-01

To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates. © 2016 S. Karger AG, Basel.

Further examination of various administration protocols of pegylated recombinant human megakaryocyte growth and development factor on thrombocytopenia in myelosuppressed mice.

PubMed

Akahori, H; Ozai, M; Ida, M; Shibuya, K; Kato, T; Miyazaki, H

1998-02-01

Thrombopoietin (TPO) is the recently isolated lineage-dominant hematopoietic factor that plays a pivotal role in the regulation of megakaryocytopoiesis and thrombopoiesis. In vivo studies have shown that daily multiple injections of pegylated human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule related to human TPO, modified with polyethylene glycol, greatly improve thrombocytopenia and in most cases anemia and neutropenia in myelosuppressed animal models. In this study, we further examined various administration protocols of PEG-rHuMGDF on thrombocytopenia in mice treated with a combination of irradiation and carboplatin. After the myelosuppressive treatment on Day 0, mice received the same amount of PEG-rHuMGDF beginning on Day 1 by a single, 3 times (on alternate days), or 7 day daily administration. A single injection of PEG-rHuMGDF significantly reduced the severity and duration of thrombocytopenia and anemia with a concomitant accelerated recovery of megakaryocytic and erythroid progenitors in the bone marrow, similar to the 2 other administration protocols. As the start of a single injection of PEG-rHuMGDF was delayed, its therapeutic effects were attenuated. These results indicate that an administration of PEG-rHuMGDF at an earlier time after the myelosuppressive treatment is necessary to improve thrombocytopenia and anemia.

Diazepam and halazepam in anxiety: some prognostic indicators.

PubMed

Rickels, K; Case, W G; Chung, H; Downing, R W; Vlahovich, J

1978-01-01

A multiple step-search regression procedure was applied to data obtained with 37 diazepam and 42 halazepam treated anxious outpatients. Good treatment outcome was predicted for those patients who reported a more adequate family adjustment, the presence of precipitating stress, and who either had no prior psychotropic drug treatment, or if they had received such treatment, had experienced a good response. Probably of greatest interest to the practicing clinician was the observation that patients high in initial anxiety but low in initial interpersonal problems improved the most with both medications. Differential drug effects indicated halazepam to do particularly poorly in less anxious patients and in those patients given a good prognosis by the doctor. Diazepam response was much less affected by these variables. It is speculated that the excessive sedating effect of the daily halazepam dosage (160 mg/d) used in this study may explain these differential drug effects. In the dosages employed, namely, diazepam 20 mg/d and halazepam 160 mg/d, diazepam produced the more consistent anti-anxiety effects. The indication that halazepam 160 mg/d was more effective than diazepam 20 mg/d in the initially sicker patients, while of interest, is probably simply a dose-related phenomenon, indicating that diazepam 20 mg/d was too low a daily dosage for severely anxious patients, a fact well known by most clinicians.

The character of sleep disturbances produced by multiple administrations of atropine the antagonist of brain muscarinic cholinergic system.

PubMed

Maglakelidze, N T; Chkhartishvili, E V; Mchedlidze, O M; Dzadzamiia, Sh Sh; Nachkebiia, N G

2012-03-01

Modification of brain muscarinic cholinergic system normal functioning can be considered as an appropriate strategy for the study of its role in sleep-wakefulness cycle basic mechanisms in general and in the course/maintenance of PS in particular. For this aim systemic application of muscarinic cholinoreceptors antagonists is significant because it gives possibility to modify functioning all of known five sub-types of muscarinic cholinoreceptors and to study the character of sleep disturbances in these conditions. Problem is very topical because the question about the intimate aspects of BMChS involvement in PS maintaining mechanisms still remains unsolved. In cats Atropine systemic administration was made once daily at 10:00 a.m. and continuous EEG registration of sleep-wakefulness cycle ultradian structure, lasting for 10 hour daily, was started immediately. In sum each animal received anti-muscarinic drugs for 12 times. Thereafter drug administrations were ceased and EEG registration of sleep-wakefulness cycle ultradian structure was continued during 10 consecutive days. On the basis of results obtained in these conditions we can conclude that brain muscarinic cholinergic system normal functioning is significant for basic mechanisms of sleep-wakefulness cycle. During wakefulness, at the level of neocortex and hippocampus, MChS supports only EEG activation, while it is one of the main factors in PS triggering and maintaining mechanisms.

Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects

PubMed Central

Rocha, José Francisco; Almeida, Luis; Falcão, Amílcar; Palma, P Nuno; Loureiro, Ana I; Pinto, Roberto; Bonifácio, Maria João; Wright, Lyndon C; Nunes, Teresa; Soares-da-Silva, Patrício

2013-01-01

Aims The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. Methods This randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days. Results Opicapone was well tolerated. Its systemic exposure increased in an approximately dose-proportional manner with an apparent terminal half-life of 1.0 to 1.4 h. Sulphation was the main metabolic pathway. Opicapone metabolites recovered in urine accounted for less than 3% of the amount of opicapone administered suggesting that bile is likely the main route of excretion. Maximum S-COMT inhibition (Emax) ranged from 69.9% to 98.0% following the last dose of opicapone. The opicapone-induced S-COMT inhibition showed a half-life in excess of 100 h, which was dose-independent and much longer than plasma drug exposure. Such a half-life translates into a putative underlying rate constant that is comparable with the estimated dissociation rate constant of the COMT–opicapone complex. Conclusion Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen. PMID:23336248

Use of interleukin-2 for management of natalizumab-associated progressive multifocal leukoencephalopathy: case report and review of literature

PubMed Central

Dubey, Divyanshu; Zhang, Yinan; Graves, Donna; DeSena, Allen D.; Frohman, Elliot; Greenberg, Benjamin

2015-01-01

A 51-year-old woman with relapsing–remitting multiple sclerosis (RRMS) and 3-year history of natalizumab use developed expressive aphasia. A brain magnetic resonance image (MRI) showed left frontotemporal and right parietal lesion with mild contrast enhancement and cerebrospinal fluid (CSF) was positive for John Cunningham virus (JCV) by polymerase chain reaction (PCR). The patient received five cycles of plasmapheresis followed by intravenous immunoglobulin. Despite this intervention, her speech deteriorated and she developed right hemiparesis. Upon referral to our institution, CSF quantitative JCV PCR was notable for 834 copies/ml. The patient was given an initial dose of 50,000 units of interleukin-2 (IL-2) subcutaneously (SQ) followed by 1 million units IL-2 SQ daily. Due to concern for immune reconstitution inflammatory syndrome (IRIS), the patient also received intravenous methylprednisone weekly. The regimen was tolerated well by the patient with no severe adverse effects. Clinically, the patient showed some improvement, and became more responsive and regained right lower extremity antigravity strength. After 12 weeks of IL-2 therapy, JCV quantitative PCR was notable for 31 copies/ml and the patient was more responsive. Due to persistence of JCV, IL-2 therapy was changed to mefloquine. At follow up after 6 months, the patient showed no clinical deterioration. PMID:27134676

IGF-1 and Chondroitinase ABC Augment Nerve Regeneration after Vascularized Composite Limb Allotransplantation.

PubMed

Kostereva, Nataliya V; Wang, Yong; Fletcher, Derek R; Unadkat, Jignesh V; Schnider, Jonas T; Komatsu, Chiaki; Yang, Yang; Stolz, Donna B; Davis, Michael R; Plock, Jan A; Gorantla, Vijay S

2016-01-01

Impaired nerve regeneration and inadequate recovery of motor and sensory function following peripheral nerve repair remain the most significant hurdles to optimal functional and quality of life outcomes in vascularized tissue allotransplantation (VCA). Neurotherapeutics such as Insulin-like Growth Factor-1 (IGF-1) and chondroitinase ABC (CH) have shown promise in augmenting or accelerating nerve regeneration in experimental models and may have potential in VCA. The aim of this study was to evaluate the efficacy of low dose IGF-1, CH or their combination (IGF-1+CH) on nerve regeneration following VCA. We used an allogeneic rat hind limb VCA model maintained on low-dose FK506 (tacrolimus) therapy to prevent rejection. Experimental animals received neurotherapeutics administered intra-operatively as multiple intraneural injections. The IGF-1 and IGF-1+CH groups received daily IGF-1 (intramuscular and intraneural injections). Histomorphometry and immunohistochemistry were used to evaluate outcomes at five weeks. Overall, compared to controls, all experimental groups showed improvements in nerve and muscle (gastrocnemius) histomorphometry. The IGF-1 group demonstrated superior distal regeneration as confirmed by Schwann cell (SC) immunohistochemistry as well as some degree of extrafascicular regeneration. IGF-1 and CH effectively promote nerve regeneration after VCA as confirmed by histomorphometric and immunohistochemical outcomes.

Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

PubMed

Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

2012-01-01

Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.

Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials

PubMed Central

Pierce, David; Corcoran, Mary; Martin, Patrick; Barrett, Karen; Inglis, Susi; Preston, Peter; Thompson, Thomas N; Willsie, Sandra K

2014-01-01

Background MMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. Aim To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. Methods In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44). Results MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) fell within the predefined equivalence range (0.80–1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild. Conclusion MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of these antibiotics. ClinicalTrials.gov identifiers NCT01442688, NCT01402947, NCT01418365, and NCT01469637. PMID:24868146

Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study.

PubMed

Cheng, Hsiu-Chi; Wu, Chung-Tai; Chang, Wei-Lun; Cheng, Wei-Chun; Chen, Wei-Ying; Sheu, Bor-Shyang

2014-12-01

Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores <6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores <6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th-28th day: 10.8% vs 28.7%, p=0.002). Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. NCT01591083. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials.

PubMed

Pierce, David; Corcoran, Mary; Martin, Patrick; Barrett, Karen; Inglis, Susi; Preston, Peter; Thompson, Thomas N; Willsie, Sandra K

2014-01-01

MMX(®) mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1-4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1-3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1-3 and once on day 4 (N=44). MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) fell within the predefined equivalence range (0.80-1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild. MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of these antibiotics. NCT01442688, NCT01402947, NCT01418365, and NCT01469637.

Associations of maternal nutrition during pregnancy and post-partum with maternal cognition and caregiving.

PubMed

Prado, Elizabeth L; Ashorn, Ulla; Phuka, John; Maleta, Kenneth; Sadalaki, John; Oaks, Brietta M; Haskell, Marjorie; Allen, Lindsay H; Vosti, Steve A; Ashorn, Per; Dewey, Kathryn G

2018-04-01

Pregnant and post-partum women require increased nutrient intake and optimal cognition, which depends on adequate nutrition, to enable reasoning and learning for caregiving. We aimed to assess (a) differences in maternal cognition and caregiving between women in Malawi who received different nutritional supplements, (b) 14 effect modifiers, and (c) associations of cognition and caregiving with biomarkers of iron, Vitamin A, B-vitamin, and fatty acid status. In a randomized controlled trial (n = 869), pregnant women daily received either multiple micronutrients (MMN), 20 g/day lipid-based nutrient supplements (LNS), or a control iron/folic acid (IFA) tablet. After delivery, supplementation continued in the MMN and LNS arms, and the IFA control group received placebo until 6 months post-partum, when cognition (n = 712), caregiving behaviour (n = 669), and biomarkers of nutritional status (n = 283) were assessed. In the full group, only one difference was significant: the IFA arm scored 0.22 SD (95% CI [0.01, 0.39], p = .03) higher than the LNS arm in mental rotation. Among subgroups of women with baseline low hemoglobin, poor iron status, or malaria, those who received LNS scored 0.4 to 0.7 SD higher than the IFA arm in verbal fluency. Breastmilk docosahexaenoic acid and Vitamin B12 concentrations were positively associated with verbal fluency and digit span forward (adjusting for covariates ps < .05). In this population in Malawi, maternal supplementation with MMN or LNS did not positively affect maternal cognition or caregiving. Maternal docosahexaenoic acid and B12 status may be important for post-partum attention and executive function. © 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.

Associations of maternal nutrition during pregnancy and post‐partum with maternal cognition and caregiving

PubMed Central

Ashorn, Ulla; Phuka, John; Maleta, Kenneth; Sadalaki, John; Oaks, Brietta M.; Haskell, Marjorie; Allen, Lindsay H.; Vosti, Steve A.; Ashorn, Per; Dewey, Kathryn G.

2017-01-01

Abstract Pregnant and post‐partum women require increased nutrient intake and optimal cognition, which depends on adequate nutrition, to enable reasoning and learning for caregiving. We aimed to assess (a) differences in maternal cognition and caregiving between women in Malawi who received different nutritional supplements, (b) 14 effect modifiers, and (c) associations of cognition and caregiving with biomarkers of iron, Vitamin A, B‐vitamin, and fatty acid status. In a randomized controlled trial (n = 869), pregnant women daily received either multiple micronutrients (MMN), 20 g/day lipid‐based nutrient supplements (LNS), or a control iron/folic acid (IFA) tablet. After delivery, supplementation continued in the MMN and LNS arms, and the IFA control group received placebo until 6 months post‐partum, when cognition (n = 712), caregiving behaviour (n = 669), and biomarkers of nutritional status (n = 283) were assessed. In the full group, only one difference was significant: the IFA arm scored 0.22 SD (95% CI [0.01, 0.39], p = .03) higher than the LNS arm in mental rotation. Among subgroups of women with baseline low hemoglobin, poor iron status, or malaria, those who received LNS scored 0.4 to 0.7 SD higher than the IFA arm in verbal fluency. Breastmilk docosahexaenoic acid and Vitamin B12 concentrations were positively associated with verbal fluency and digit span forward (adjusting for covariates ps < .05). In this population in Malawi, maternal supplementation with MMN or LNS did not positively affect maternal cognition or caregiving. Maternal docosahexaenoic acid and B12 status may be important for post‐partum attention and executive function. PMID:29098783

Speechlessness in Gilles de la Tourette Syndrome: Cannabis-Based Medicines Improve Severe Vocal Blocking Tics in Two Patients

PubMed Central

Jakubovski, Ewgeni; Müller-Vahl, Kirsten

2017-01-01

We report the cases of two young German male patients with treatment-resistant Tourette syndrome (TS), who suffer from incapacitating stuttering-like speech disfluencies caused by vocal blocking tics and palilalia. Case 1: a 19-year old patient received medical cannabis at a dose of 1 × 0.1 g cannabis daily. Case 2: a 16-year old patient initially received dronabinol at a maximum dose of 22.4–33.6 mg daily. Both treatments provided significant symptom improvement of vocal blocking tics as well as of comorbid conditions and were well tolerated. Thus, cannabis-based medicine appears to be effective in treatment-resistant TS patients with vocal blocking tics. PMID:28796166

Speechlessness in Gilles de la Tourette Syndrome: Cannabis-Based Medicines Improve Severe Vocal Blocking Tics in Two Patients.

PubMed

Jakubovski, Ewgeni; Müller-Vahl, Kirsten

2017-08-10

We report the cases of two young German male patients with treatment-resistant Tourette syndrome (TS), who suffer from incapacitating stuttering-like speech disfluencies caused by vocal blocking tics and palilalia. Case 1: a 19-year old patient received medical cannabis at a dose of 1 × 0.1 g cannabis daily. Case 2: a 16-year old patient initially received dronabinol at a maximum dose of 22.4-33.6 mg daily. Both treatments provided significant symptom improvement of vocal blocking tics as well as of comorbid conditions and were well tolerated. Thus, cannabis-based medicine appears to be effective in treatment-resistant TS patients with vocal blocking tics.

Ulipristal acetate versus leuprolide acetate for uterine fibroids.

PubMed

Donnez, Jacques; Tomaszewski, Janusz; Vázquez, Francisco; Bouchard, Philippe; Lemieszczuk, Boguslav; Baró, Francesco; Nouri, Kazem; Selvaggi, Luigi; Sodowski, Krzysztof; Bestel, Elke; Terrill, Paul; Osterloh, Ian; Loumaye, Ernest

2012-02-02

The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%. Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate). Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.).

Pharmacokinetic and Pharmacodynamic Properties and Tolerability of Single- and multiple-dose Once-daily Empagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, in Chinese Patients With Type 2 Diabetes Mellitus.

PubMed

Zhao, Xia; Cui, Yimin; Zhao, Shuai; Lang, Benjamin; Broedl, Uli C; Salsali, Afshin; Pinnetti, Sabine; Macha, Sreeraj

2015-07-01

The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties and tolerability of the oral once-daily sodium glucose cotransporter 2 inhibitor empagliflozin, given in single and multiple 10 and 25 mg doses in Chinese patients with type 2 diabetes mellitus (T2DM). In a double-blind, placebo-controlled, parallel-group study, Chinese patients with T2DM were randomly assigned to receive a single dose of empagliflozin 10 or 25 mg or placebo on day 1 and once daily on days 3 to 9. A total of 24 patients were enrolled (14 men, 10 women; median age, 53.5 years; empagliflozin 10 mg, n = 9; empagliflozin 25 mg, n = 9; and placebo, n = 6). After both single- and multiple-dose administration, empagliflozin 10 and 25 mg were rapidly absorbed, reaching peak plasma concentrations within 1 to 1.5 hours (median), with plasma levels declining biphasically. Empagliflozin exposure increased roughly dose proportionally between 10 and 25 mg. Mean terminal elimination half-life values at steady state were 13.9 and 12.1 hours with empagliflozin 10 and 25 mg, respectively. Mean (SD) changes from baseline in 24-hour urinary glucose excretion (UGE) on day 1 were +87.7 (22.9) and +82.8 (18.8) g with empagliflozin 10 and 25 mg, respectively, compared with -1.0 (2.8) g with placebo, and on day 9 were +95.8 (24.1), +82.6 (34.8) g with empagliflozin 10 and 25 mg, respectively, compared with -4.1 (6.4) g with placebo. Mean (SD) changes from baseline in fasting plasma glucose (FPG) on day 2 were -18.7 (17.2) mg/dL and -25.8 (19.6) mg/dL with empagliflozin 10 and 25 mg, respectively, compared with -4.2 (15.2) mg/dL with placebo, and on day 9, were -25.6 (20.7) mg/dL and -31.4 (26.9) mg/dL with empagliflozin 10 and 25 mg, respectively, compared to -3.7 (7.5) mg/dL with placebo. On day 10, mean changes in weight were -1.1, -1.6, and +0.5 kg with empagliflozin 10 and 25 mg and placebo, respectively. Overall, empagliflozin 10 and 25 mg had safety profiles similar to that of placebo. There were no reports of hypoglycemia, urinary tract infections, or genital infections. Results with single and multiple doses of empagliflozin 10 and 25 mg suggest linear pharmacokinetic properties in Chinese patients with T2DM, with a safety profile similar to that of placebo. Empagliflozin treatment was associated with increases in UGE and reductions in FPG compared with placebo. ClinicalTrials.gov identifier: NCT01316341. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Women's experiences of daily life after anterior cervical decompression and fusion surgery: A qualitative interview study.

PubMed

Hermansen, Anna; Peolsson, Anneli; Kammerlind, Ann-Sofi; Hjelm, Katarina

2016-04-01

To explore and describe women's experiences of daily life after anterior cervical decompression and fusion surgery. Qualitative explorative design. Fourteen women aged 39-62 years (median 52 years) were included 1.5-3 years after anterior cervical decompression and fusion for cervical disc disease. Individual semi-structured interviews were analysed by qualitative content analysis with an inductive approach. The women described their experiences of daily life in 5 different ways: being recovered to various extents; impact of remaining symptoms on thoughts and feelings; making daily life work; receiving support from social and occupational networks; and physical and behavioural changes due to interventions and encounters with healthcare professionals. This interview study provides insight into women's daily life after anterior cervical decompression and fusion. Whilst the subjects improved after surgery, they also experienced remaining symptoms and limitations in daily life. A variety of mostly active coping strategies were used to manage daily life. Social support from family, friends, occupational networks and healthcare professionals positively influenced daily life. These findings provide knowledge about aspects of daily life that should be considered in individualized postoperative care and rehabilitation in an attempt to provide better outcomes in women after anterior cervical decompression and fusion.

A Twitter-based survey on marijuana concentrate use.

PubMed

Daniulaityte, Raminta; Zatreh, Mussa Y; Lamy, Francois R; Nahhas, Ramzi W; Martins, Silvia S; Sheth, Amit; Carlson, Robert G

2018-06-01

The purpose of this paper is to analyze characteristics of marijuana concentrate users, describe patterns and reasons of use, and identify factors associated with daily use of concentrates among U.S.-based cannabis users recruited via a Twitter-based online survey. An anonymous Web-based survey was conducted in June 2017 with 687 U.S.-based cannabis users recruited via Twitter-based ads. The survey included questions about state of residence, socio-demographic characteristics, and cannabis use including marijuana concentrates. Multiple logistic regression analyses were conducted to identify characteristics associated with lifetime and daily use of marijuana concentrates. Almost 60% of respondents were male, 86% were white, and the mean age was 43.0 years. About 48% reported marijuana concentrate use. After adjusting for multiple testing, significant predictors of concentrate use included: living in "recreational" (AOR = 2.04; adj. p = .042) or "medical, less restrictive" (AOR = 1.74; adj. p = .030) states, being younger (AOR = 0.97, adj. p = .008), and daily herbal cannabis use (AOR = 2.57, adj. p = .008). Out of 329 marijuana concentrate users, about 13% (n = 44) reported daily/near daily use. Significant predictors of daily concentrate use included: living in recreational states (AOR = 3.59, adj. p = .020) and using concentrates for therapeutic purposes (AOR = 4.34, adj. p = .020). Living in states with more liberal marijuana policies is associated with greater likelihood of marijuana concentrate use and with more frequent use. Characteristics of daily users, in particular, patterns of therapeutic use warrant further research with community-recruited samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of relaxation training according to Yoga In Daily Life® system on perceived stress after breast cancer surgery.

PubMed

Kovačič, Tine; Kovačič, Miha

2011-03-01

The purpose of this pilot study was to gather information on the immediate and short-term effects of relaxation training according to Yoga In Daily Life(®) (YIDL) system on the psychological distress of breast cancer patients. 32 patients at the Institute for Oncology of Ljubljana were randomized to the experimental (N=16) and to the control group (N=16). Both groups received the same standard physiotherapy for 1 week, while the experimental group additionally received a group relaxation training sessions according to YIDL(®) system. At discharge the experimental group was issued with audiocassette recordings containing the similar instructions for relaxation training to be practiced individually at home (for further 3 weeks). An experimental repeated measures design was used to investigate the differences over 1 month period in stress levels, changes in mental health and psychological parameters. Measures were obtained at three time points during the study period: baseline, at 1 week, and at 4 weeks, by blinded investigators using standardized questionnaires General Health Questionnaire-12 (GHQ-12), Rotterdam Symptom Checklist (RSCL) psychological subscale, Perceived Stress Scale (PSS). Patients who received relaxation training reported feeling significantly less distressed during hospitalization and after discharge-period than did the controls that did not receive relaxation training. The results indicate that relaxation training according to Yoga in Daily Life(®) system could be useful clinical physiotherapy intervention for breast cancer patients experiencing psychological distress. Although this kind of relaxation training can be applied to clinical oncology in Slovenia, more studies need to be done. © The Author(s) 2011

Efficacy and safety of empagliflozin twice daily versus once daily in patients with type 2 diabetes inadequately controlled on metformin: a 16-week, randomized, placebo-controlled trial.

PubMed

Ross, S; Thamer, C; Cescutti, J; Meinicke, T; Woerle, H J; Broedl, U C

2015-07-01

Patients with type 2 diabetes mellitus (T2DM) with a glycated haemoglobin (HbA1c) level ≥7 and ≤10% were randomized to receive empagliflozin 12.5 mg twice daily (n = 219), 25 mg once daily (n = 218), 5 mg twice daily (n = 219) or 10 mg once daily (n = 220), or placebo (n = 107) as add-on to stable-dose metformin immediate release (IR) twice daily for 16 weeks. The primary endpoint was change from baseline in HbA1c at week 16. At week 16, change from baseline in HbA1c with empagliflozin twice daily was non-inferior to empagliflozin once daily and vice versa. The adjusted mean (95% confidence interval) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was -0.11% (-0.26, 0.03), and with empagliflozin 5 mg twice daily versus 10 mg once daily it was -0.02% (-0.16, 0.13). All empagliflozin regimens were well tolerated; thus, when used as add-on to metformin IR in patients with T2DM, the therapeutic effect of empagliflozin twice-daily and once-daily regimens can be considered equivalent. © 2015 John Wiley & Sons Ltd.

Daily-Life Vocabulary: A Cinderella Component in Iranian High School Context

ERIC Educational Resources Information Center

Aminifard, Yasser; Askari, Hamdollah; Khajehei, Hassan

2015-01-01

This study reports on investigating the difference between Iranian high school students' performance on Academic Word (AW) and Daily-Life Word (DLW) tests. To this end, a number of 120 male senior high school students were randomly selected from twelve high schools in Gachsaran to serve as the participants of the study. Two multiple-choice tests,…

Progress Monitoring Using Direct Behavior Rating Single Item Scales in a Multiple-Baseline Design Study of the Daily Report Card Intervention

ERIC Educational Resources Information Center

Fabiano, Gregory A.; Pyle, Kellina; Kelty, Mary Bridget; Parham, Brittany R.

2017-01-01

Direct behavior rating (DBR) may be a viable assessment for documenting current areas of impaired functioning and progress monitoring students' response to a behavioral intervention. Challenging behaviors are often addressed in general education settings using interventions such as the daily report card (DRC). To best implement and monitor such…

Children's Daily Well-Being: The Role of Mothers', Teachers', and Siblings' Autonomy Support and Psychological Control

ERIC Educational Resources Information Center

van der Kaap-Deeder, Jolene; Vansteenkiste, Maarten; Soenens, Bart; Mabbe, Elien

2017-01-01

This study examined the unique relations between multiple sources (i.e., mothers, teachers, and siblings) of perceived daily autonomy support and psychological control and children's basic psychological needs and well-being. During 5 consecutive days, 2 children from 154 families (M[subscript age] youngest child = 8.54 years; SD = 0.89 and…

Compositional data analysis for physical activity, sedentary time and sleep research.

PubMed

Dumuid, Dorothea; Stanford, Tyman E; Martin-Fernández, Josep-Antoni; Pedišić, Željko; Maher, Carol A; Lewis, Lucy K; Hron, Karel; Katzmarzyk, Peter T; Chaput, Jean-Philippe; Fogelholm, Mikael; Hu, Gang; Lambert, Estelle V; Maia, José; Sarmiento, Olga L; Standage, Martyn; Barreira, Tiago V; Broyles, Stephanie T; Tudor-Locke, Catrine; Tremblay, Mark S; Olds, Timothy

2017-01-01

The health effects of daily activity behaviours (physical activity, sedentary time and sleep) are widely studied. While previous research has largely examined activity behaviours in isolation, recent studies have adjusted for multiple behaviours. However, the inclusion of all activity behaviours in traditional multivariate analyses has not been possible due to the perfect multicollinearity of 24-h time budget data. The ensuing lack of adjustment for known effects on the outcome undermines the validity of study findings. We describe a statistical approach that enables the inclusion of all daily activity behaviours, based on the principles of compositional data analysis. Using data from the International Study of Childhood Obesity, Lifestyle and the Environment, we demonstrate the application of compositional multiple linear regression to estimate adiposity from children's daily activity behaviours expressed as isometric log-ratio coordinates. We present a novel method for predicting change in a continuous outcome based on relative changes within a composition, and for calculating associated confidence intervals to allow for statistical inference. The compositional data analysis presented overcomes the lack of adjustment that has plagued traditional statistical methods in the field, and provides robust and reliable insights into the health effects of daily activity behaviours.

Burden among male caregivers assisting people with multiple sclerosis.

PubMed

Buchanan, Robert J; Radin, Dagmar; Huang, Chunfeng

2010-12-01

Caregiver burden is a multidimensional response to many factors associated with providing assistance to people with multiple sclerosis (MS), including physical, psychological, emotional, and social stressors. The aim of this analysis was to identify the characteristics of male informal caregivers, the assistance provided, and the people receiving assistance who were associated with the burden of care. Data were collected from a national survey (which included the Mental Component Summary of the SF-8 Health Survey) of informal caregivers and analyzed using an ordered logistic regression model to identify characteristics associated with burden among male informal caregivers. Greater burden among male caregivers was associated with significantly greater hours per week providing assistance (P = 0.009) and significantly greater restriction on the caregiver's ability to perform daily activities (P < 0.001) due to assisting the person with MS. We found a strong association between the perception of burden and the mental health status of the male caregiver (P < 0.001). Our findings highlight the strong association of caregiver burden and the Mental Component Summary of the SF-8. Reducing burden may improve the mental health of informal caregivers. Health professionals treating either male caregivers or people with MS should be sensitive to the impact that providing assistance has on the mental health of informal caregivers. Copyright © 2010. Published by EM Inc USA.

High EDSS can predict risk for upper urinary tract damage in patients with multiple sclerosis.

PubMed

Ineichen, Benjamin V; Schneider, Marc P; Hlavica, Martin; Hagenbuch, Niels; Linnebank, Michael; Kessler, Thomas M

2018-04-01

Neurogenic lower urinary tract dysfunction (NLUTD) is very common in patients with multiple sclerosis (MS), and it might jeopardize renal function and thereby increase mortality. Although there are well-known urodynamic risk factors for upper urinary tract damage, no clinical prediction parameters are available. We aimed to assess clinical parameters potentially predicting urodynamic risk factors for upper urinary tract damage. A consecutive series of 141 patients with MS referred from neurologists for primary neuro-urological work-up including urodynamics were prospectively evaluated. Clinical parameters taken into account were age, sex, duration, and clinical course of MS and Expanded Disability Status Scale (EDSS). Multivariate modeling revealed EDSS as a clinical parameter significantly associated with urodynamic risk factors for upper urinary tract damage (odds ratio = 1.34, 95% confidence interval (CI) = 1.06-1.71, p = 0.02). Using receiver operator characteristic (ROC) curves, an EDSS of 5.0 as cutoff showed a sensitivity of 86%-87% and a specificity of 52% for at least one urodynamic risk factor for upper urinary tract damage. High EDSS is significantly associated with urodynamic risk factors for upper urinary tract damage and allows a risk-dependent stratification in daily neurological clinical practice to identify MS patients requiring further neuro-urological assessment and treatment.

Impact of self-reported multiple chemical sensitivity on everyday life: a qualitative study.

PubMed

Skovbjerg, Sine; Brorson, Stig; Rasmussen, Alice; Johansen, Jeanne Duus; Elberling, Jesper

2009-08-01

Multiple chemical sensitivity (MCS) is a descriptive term covering symptoms attributed to exposure to common airborne chemicals. There are no internationally accepted criteria, but it has been suggested that MCS is a chronic and disabling condition. However, details of the impact of MCS on everyday life are limited. To describe the impact of MCS on everyday life, strategies for managing the condition, and experiences with healthcare management. A focus group study was conducted, including two interviews with a sample of six women and six men between 27 and 78 years of age, a duration of MCS of at least 1 year, and with different occupational conditions. MCS may severely influence different aspects of everyday life, including lifestyle, social relations, and occupational conditions. Avoiding common airborne chemicals was the most prevalent coping strategy, which implied creating a chemical-free living space and limiting social activities. Experiences with healthcare management were overall reported as negative in terms of not receiving acknowledgement of the reported symptoms. MCS may have serious implications for daily functioning. Further research on individual consequences and the social and psychological factors that may be associated with MCS is needed in order to add to our understanding of this condition and to the provision of more satisfactory healthcare.

Effects of transcranial random noise stimulation (tRNS) on affect, pain and attention in multiple sclerosis.

PubMed

Palm, Ulrich; Chalah, Moussa A; Padberg, Frank; Al-Ani, Tarik; Abdellaoui, Mohamed; Sorel, Marc; Dimitri, Dalia; Créange, Alain; Lefaucheur, Jean-Pascal; Ayache, Samar S

2016-01-01

Pain and cognitive impairment are frequent symptoms in patients with multiple sclerosis (MS). Neglecting experimental pain and paying attention to demanding tasks is reported to decrease the pain intensity. Little is known about the interaction between chronic neuropathic pain and attention disorders in MS. Recently, transcranial direct current stimulation (tDCS) was used to modulate various cognitive and motor symptoms in MS. We aimed to study the effects of transcranial random noise stimulation (tRNS), a form of transcranial electric stimulation, over the left dorsolateral prefrontal cortex (DLPFC) on attention and neuropathic pain in MS patients. 16 MS patients were included in a randomized, sham-controlled, cross-over study. Each patient randomly received two tRNS blocks, separated by three weeks of washout interval. Each block consisted of three consecutive daily sessions of either active or sham tRNS. The patients were evaluated for pain, attention and mood and further underwent an electrophysiological evaluation. Compared to sham, tRNS showed a trend to decrease the N2-P2 amplitudes of pain related evoked potentials and improve pain ratings. Attention performance and mood scales did not change after stimulations. This study suggests the role of tRNS in pain modulation, which could have been more evident with longer stimulation protocols.

Exploring inter-task transfer following a CO-OP approach with four children with DCD: A single subject multiple baseline design.

PubMed

Capistran, Julie; Martini, Rose

2016-10-01

Cognitive Orientation to daily Occupational Performance (CO-OP) approach has been shown to be effective for improving the performance of tasks worked on in therapy and the use of cognitive strategies. No study to date seems to have explored its effectiveness for improving performance of untrained tasks (inter-task transfer) in children with Developmental Coordination Disorder (DCD). This study aimed to determine whether CO-OP leads to improved performance in an untrained task. A single-subject design with multiple baselines across skills was adopted, with three replications. Four children with DCD (7-12years) received 10 sessions of CO-OP intervention where each child worked on three tasks during therapy sessions and a fourth task was identified, but not worked on, to verify inter-task transfer. Task performance was rated over four phases (baseline, intervention, post-intervention, follow-up) using the Performance Quality Rating Scale (PQRS-OD). Graphed data was statistically analyzed using a two or three standard deviation band method. Significant improvement was obtained for 11 of 12 tasks worked on during therapy and for two of the four untrained tasks. These results indicate that the effectiveness of CO-OP to improve untrained tasks in children merit further exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

Outsourcing issues for nurse practitioner practices.

PubMed

Mackey, Thomas A; McNiel, Nancy O; Klingensmith, Kenneth

2004-01-01

Nurse practitioner managed practices face multiple business and clinical processes. While most practice managers are prepared as clinicians, they are not well prepared to deal with the daily multiple business infrastructure issues they face. To provide for increased efficiency and effectiveness, nurse practitioner practices should consider outsourcing context business functions.

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.

PubMed

Kourlaba, Georgia; Dimopoulos, Meletios A; Pectasides, Dimitrios; Skarlos, Dimosthenis V; Gogas, Helen; Pentheroudakis, George; Koutras, Angelos; Fountzilas, George; Maniadakis, Nikos

2015-07-01

The aim of this study was to compare the effectiveness of prophylactic single fixed dose of pegfilgrastim and daily administration of filgrastim on febrile neutropenia (FN), severe neutropenia, treatment delay, and dose reduction in patients with breast cancer receiving dose-dense adjuvant chemotherapy. A retrospective cohort study with 1058 breast cancer patients matched by age and chemotherapy was conducted. The primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>10 % reduction of the dose planned), and treatment delay (dose given more than 2 days later). Eighteen episodes of FN (3.4%) in the filgrastim group and 23 (4.3%) in the pegfilgrastim group (p = 0.500) were recorded. More than half of the total episodes (27/41) occurred during the first 4 cycles of treatment. Patients who received filgrastim were almost three times more likely to experience a severe neutropenia episode and were significantly more likely to experience a dose reduction (18.5%) compared to those who received pegfilgrastim (10.8%) (p < 0.001). The percentage of patients, who received their planned dose on time, was significantly lower in patients receiving filgrastim (58%) compared to those receiving pegfilgrastim (72.4%, p < 0.001). No significant difference was detected on FN rate between daily administration of filgrastim and single administration of pegfilgrastim. However, patients receiving pegfilgrastim had a significantly lower rate of severe neutropenia, as well as dose reduction and treatment delay, thus, achieving a higher dose density.

Wavelet regression model in forecasting crude oil price

NASA Astrophysics Data System (ADS)

Hamid, Mohd Helmie; Shabri, Ani

2017-05-01

This study presents the performance of wavelet multiple linear regression (WMLR) technique in daily crude oil forecasting. WMLR model was developed by integrating the discrete wavelet transform (DWT) and multiple linear regression (MLR) model. The original time series was decomposed to sub-time series with different scales by wavelet theory. Correlation analysis was conducted to assist in the selection of optimal decomposed components as inputs for the WMLR model. The daily WTI crude oil price series has been used in this study to test the prediction capability of the proposed model. The forecasting performance of WMLR model were also compared with regular multiple linear regression (MLR), Autoregressive Moving Average (ARIMA) and Generalized Autoregressive Conditional Heteroscedasticity (GARCH) using root mean square errors (RMSE) and mean absolute errors (MAE). Based on the experimental results, it appears that the WMLR model performs better than the other forecasting technique tested in this study.

Dialysis adequacy of Asian patients receiving small volume continuous ambulatory peritoneal dialysis.

PubMed

Szeto, C C; Lai, K N; Yu, A W; Leung, C B; Ho, K K; Mak, T W; Li, P K; Lam, C W

1997-08-01

The usage of three x 2 liter daily exchanges is adopted as the standard CAPD regime in Hong Kong over the last 10 years due to budgetary constraint. This dialysis prescription is considered suboptimal in Western standard. However, the necessity of maintaining Kt/V > 1.7 for CAPD dialysis adequacy is not unanimously agreed. We performed a cross-sectional study of 117 patients on CAPD. Seventy-eight percent of our patients had 3 x 2 liter daily exchange while the rest had 4 daily exchanges. Fifteen percent of patients were diabetic. Patients with Kt/V < 1.7 were similar to those with Kt/V > 1.7 in age, duration of CAPD, BUN, plasma creatinine, albumin, peritonitis rate, and incidence of hypertension. Patients with Kt/V > or = 1.7 had higher hemoglobin, higher nPCR, more residual renal function; and more of them received 4 daily exchanges. Their peritoneal permeability did not differ. Their employment and rehabilitation status was also similar. Our 5-year survival was 79% despite a lower Kt/V. Notably, the protein catabolic rate of our patients was higher than that in Western patients. This is likely due to dietary difference. Our study suggests small-volume dialysis may be acceptable in Asian population with smaller body size given the financial constraint.

Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradley, Kristin A., E-mail: bradley@humonc.wisc.edu; Zhou Tianni; McNall-Knapp, Rene Y.

2013-01-01

Purpose: To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. Methods and Materials: Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to standard dose irradiation. Radiation therapy was administered at a daily dose of 1.8 Gy for 30 treatments overmore » 6 weeks. The total dose was 54 Gy. Results: Sixty eligible children received MGd daily, concurrent with 6 weeks of radiation therapy. The estimated 1-year EFS was 18% {+-} 5%, and the estimated 1-year OS was 53% {+-} 6.5%. The most common grade 3 to 4 toxicities were lymphopenia, transient elevation of liver transaminases, and hypertension. Conclusions: Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.« less

Evolution of the treatment of attention-deficit/hyperactivity disorder in children: a review.

PubMed

Findling, Robert L

2008-05-01

Efficacious and well-tolerated medications are available for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants such as methylphenidate (MPH) and amphetamines are the most widely used medications approved by the US Food and Drug Administration for the treatment of ADHDin children. This article reviews the literature on the development and use of medications for the treatment of ADHD in children. A search of MEDLINE was conducted toidentify relevant studies and critical reviews on the treatment of ADHD in children. The main criteria for inclusion of a study were that it have a controlled design, enroll >100 subjects if a clinical trial and >20 subjects if a classroom study, assess symptoms with the most widely used scales and tests,and be published from 2000 to 2008.A few older pivotal studies were also included. Many studies have reported the long-term efficacy and tolerability of immediate-release formulations of MPH. The disadvantages of such formulations include the need for multiple daily dosing and a potential for abuse. Various extended-release formulations of MPH have been found effective in controlled studies enrolling large numbers of children with ADHD. The efficacy and tolerability of dexmethylphenidate, the active D-isomer of MPH, in an extended-release formulation have also been reported. An extended-release formulation of mixed amphetamine salts (MMAS-XR) that is dosed once daily has been found to be efficacious and well tolerated. The non-stimulant atomoxetine has been reported to be well tolerated and efficacious, although it may not be as effective as stimulants; this formulation is, however, less likely than stimulants to be associated with abuse and diversion. A recently approved prodrug stimulant, lisdexamfetamine dimesylate (LDX), was developed to provide a long duration of effect that is consistent throughout the day, with a reduced potential for abuse. In a placebo-controlled study in children with ADHD, less intersubject variability in T(max), C(max), and AUC from time zero to the last quantifiable concentration was seen in the 8 subjects who received LDX (percent coefficient of variation, 15.3, 20.3, and 21.6, respectively) compared with the 9 subjects who received MAS-XR (52.8, 44.0, and 42.8).In 2 clinical trials, significantly greater improvements in teacher and parent ratings of ADHD symptoms were seen with LDX compared with placebo (P<0.001).A study of the abuse potential of LDX evaluated subjective responses to the effects of oral LDX and immediate-release d-amphetamine in adults with a history of stimulant abuse. LDX was associated with a significantly lower abuse-related liking effect than d-aamphetamine (P = 0.039). Currently available treatments for ADHD in children are efficacious and well tolerated, but many of them are limited by the requirement for multiple daily dosing and abuse potential. LDX, a long-acting prodrug of d-amphetamine, has been reported to be effective and appears to overcome some of these limitations.

Delaying cognitive and physical decline through multidomain interventions for residents with mild-to-moderate dementia in dementia care units in Taiwan: A prospective cohort study.

PubMed

Liang, Chih-Kuang; Chou, Ming-Yueh; Chen, Liang-Yu; Wang, Kuei-Yu; Lin, Shih-Yi; Chen, Liang-Kung; Lin, Yu-Te; Liu, Tsung-Yun; Loh, Ching-Hui

2017-04-01

To develop experimental multi-domain interventions for older people with mild-to-moderate dementia, and to evaluate the effect of delaying cognitive and physical decline, and improvement or prevention of geriatric syndromes during 1-year follow up. Participants aged 65 years and older with mild-to-moderate dementia (clinical dementia rating [CDR] 1 or 2) were grouped as intervention in Jia-Li Veterans Home and usual care model in the community (Memory clinic). All residents in Jia-Li Veterans Home received comprehensive intervention, including Multi-disciplinary team consultation and intervention, Multi-component non-pharmacological management, geriatric syndromes survey and intervention by CGA, and a dementia friendly medical Green channel Approach (2MCGA). The decline of cognitive and physical function are determined by the change of Mini-Mental State Examination score, CDR and the sum of CDR box, as well as activities of daily living based on the Barthel Index. We also screened geriatric syndromes at baseline and 1 year later. Participants in the intervention group were older and had a lower educational level, lower body mass index, poor baseline activities of daily living function, lower visual impairment, and higher rates of hearing impairment, polypharmacy and risk of malnutrition. The residents receiving 2MCGA had lower baseline Mini-Mental State Examination scores, and higher CDR. For residents in Jia-Li Veterans Home, all cognitive measurements except Mini-Mental State Examination were significantly associated with delaying the decline of cognition after analyzing by multiple linear regression, and multivariate logistic regression also showed that patients living in the community was independently associated with a higher odds ratio for activities of daily living decline (3.180, 95% CI 1.384-7.308, P = 0.006). There are also more improvement in their baseline geriatric syndromes and suffered less from new geriatric syndromes, including falls, urinary incontinence, and risk of malnutrition. The 2MCGA intervention shows strong delays in the decline of cognition and physical function for older residents with mild-to-moderate dementia. Furthermore, this strategy can also improve or prevent the onset of new geriatric syndromes, especially fall episodes, urinary incontinence and risk of malnutrition. Geriatr Gerontol Int 2017; 17 (Suppl. 1): 36-43. © 2017 Japan Geriatrics Society.

Social differences in who receives questions and advice about smoking habits when visiting primary care - Results from a population based study in Sweden in 2012.

PubMed

Molarius, Anu; Hellstrand, Mats; Engström, Sevek

2017-03-01

The aim of this study was to examine whether there are social disparities in who receives questions and advice on smoking habits when visiting primary care and whether these disparities can be explained by differences in smoking habits. The study is based on 30,188 individuals aged 16-84 years who responded to a population survey questionnaire in 2012 in four counties in mid-Sweden (response rate 51%). Multivariate logistic regression models were used in statistical analyses. A total of 32% of those who visited a health care centre during the last three months reported that they were asked about their smoking habits during their latest visit, 6% received advice. In general, daily smokers received more often questions, and especially advice, than non-smokers. Persons with low education received more advice than persons with high education due to higher smoking prevalence. However, persons on disability pension and the unemployed were less frequently asked about their smoking habits than employees even though they smoke more. Women received less often questions and advice than men. Persons born outside the Nordic countries received advice twice as often as native Swedes regardless of whether they were daily smokers or not. In Sweden, those who are asked and, in particular, receive advice about changing their smoking habits while visiting primary care are mainly those who need it most. But the findings also imply that measures to reduce smoking should be intensified for women and are perhaps too intense for persons born outside the Nordic countries.

Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand.

PubMed

Walsh, D S; Looareesuwan, S; Wilairatana, P; Heppner, D G; Tang, D B; Brewer, T G; Chokejindachai, W; Viriyavejakul, P; Kyle, D E; Milhous, W K; Schuster, B G; Horton, J; Braitman, D J; Brueckner, R P

1999-10-01

WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

Do Medicaid incentive payments boost quality? Florida's direct care staffing adjustment program.

PubMed

Hyer, Kathryn; Thomas, Kali S; Johnson, Christopher E; Harman, Jeffrey S; Weech-Maldonado, Robert

2013-01-01

Beginning in April 2000 and continuing for 21 months, Florida's legislature allocated $31.6 million (annualized) to nursing homes through a Medicaid direct care staffing adjustment. Florida's legislature paid the highest incentives to nursing homes with the lowest staffing levels and the greatest percentage of Medicaid residents--the bottom tier of quality. Using Donabedian's structure-process-outcomes framework, this study tracks changes in staffing, wages, process of care, and outcomes. The incentive payments increased staffing and wages in nursing home processes (decreased restraint use and feeding tubes) for the facilities receiving the largest amount of money but had no change on pressure sores or decline in activities of daily living. The group receiving the lowest incentives payment (those highest staffed at baseline) saw significant improvement in two quality measures: pressure sores and decline in activities of daily living. All providers receiving more resources improved on deficiency scores, suggesting more Medicaid spending improves quality of care regardless of total incentive payments.

Acoustic MIMO communications in a very shallow water channel

NASA Astrophysics Data System (ADS)

Zhou, Yuehai; Cao, Xiuling; Tong, Feng

2015-12-01

Underwater acoustic channels pose significant difficulty for the development of high speed communication due to highly limited band-width as well as hostile multipath interference. Enlightened by rapid progress of multiple input multiple output (MIMO) technologies in wireless communication scenarios, MIMO systems offer a potential solution by enabling multiple spatially parallel communication channels to improve communication performance as well as capacity. For MIMO acoustic communications, deep sea channels offer substantial spatial diversity among multiple channels that can be exploited to address simultaneous multipath and co-channel interference. At the same time, there are increasing requirements for high speed underwater communication in very shallow water area (for example, a depth less than 10 m). In this paper, a space-time multichannel adaptive receiver consisting of multiple decision feedback equalizers (DFE) is adopted as the receiver for a very shallow water MIMO acoustic communication system. The performance of multichannel DFE receivers with relatively small number of receiving elements are analyzed and compared with that of the multichannel time reversal receiver to evaluate the impact of limited spatial diversity on multi-channel equalization and time reversal processing. The results of sea trials in a very shallow water channel are presented to demonstrate the feasibility of very shallow water MIMO acoustic communication.

Monte Carlo Analysis of Molecule Absorption Probabilities in Diffusion-Based Nanoscale Communication Systems with Multiple Receivers.

PubMed

Arifler, Dogu; Arifler, Dizem

2017-04-01

For biomedical applications of nanonetworks, employing molecular communication for information transport is advantageous over nano-electromagnetic communication: molecular communication is potentially biocompatible and inherently energy-efficient. Recently, several studies have modeled receivers in diffusion-based molecular communication systems as "perfectly monitoring" or "perfectly absorbing" spheres based on idealized descriptions of chemoreception. In this paper, we focus on perfectly absorbing receivers and present methods to improve the accuracy of simulation procedures that are used to analyze these receivers. We employ schemes available from the chemical physics and biophysics literature and outline a Monte Carlo simulation algorithm that accounts for the possibility of molecule absorption during discrete time steps, leading to a more accurate analysis of absorption probabilities. Unlike most existing studies that consider a single receiver, this paper analyzes absorption probabilities for multiple receivers deterministically or randomly deployed in a region. For random deployments, the ultimate absorption probabilities as a function of transmitter-receiver distance are shown to fit well to power laws; the exponents derived become more negative as the number of receivers increases up to a limit beyond which no additional receivers can be "packed" in the deployment region. This paper is expected to impact the design of molecular nanonetworks with multiple absorbing receivers.

Tadalafil once daily and extracorporeal shock wave therapy in the management of patients with Peyronie's disease and erectile dysfunction: results from a prospective randomized trial.

PubMed

Palmieri, A; Imbimbo, C; Creta, M; Verze, P; Fusco, F; Mirone, V

2012-04-01

Extracorporeal shock wave therapy improves erectile function in patients with Peyronie's disease. However, erectile dysfunction still persists in many cases. We aimed to investigate the effects of extracorporeal shock wave therapy plus tadalafil 5 mg once daily in the management of patients with Peyronie's disease and erectile dysfunction not previously treated. One hundred patients were enrolled in a prospective, randomized, controlled study. Patients were randomly allocated to receive either extracorporeal shock wave therapy alone for 4 weeks (n = 50) or extracorporeal shock wave therapy plus tadalafil 5 mg once daily for 4 weeks (n = 50). Main outcome measures were: erectile function (evaluated through the shortened version of the International Index of Erectile Function), pain during erection (evaluated through a Visual Analog Scale), plaque size, penile curvature and quality of life (evaluated through an internal questionnaire). Follow-up evaluations were performed after 12 and 24 weeks. In both groups, at 12 weeks follow-up, mean Visual Analog Scale score, mean International Index of Erectile Function score and mean quality of life score ameliorated significantly while mean plaque size and mean curvature degree were unchanged. Intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and quality of life score in patients receiving the combination. After 24 weeks, intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and mean quality of life score in patients that received extracorporeal shock wave therapy plus tadalafil. In conclusion extracorporeal shock wave therapy plus tadalafil 5 mg once daily may represent a valid conservative strategy for the management of patients with Peyronie's disease and erectile dysfunction. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Evidence for a pharmacokinetic interaction between eslicarbazepine and rosuvastatin: Potential effects on xenobiotic transporters.

PubMed

Gidal, Barry E; Mintzer, Scott; Schwab, Matthias; Schutz, Ralph; Kharidia, Jahnavi; Blum, David; Grinnell, Todd; Sunkaraneni, Soujanya

2017-09-01

Patients with partial-onset seizures and comorbid cardiovascular disease may concomitantly receive eslicarbazepine acetate (ESL), an antiepileptic drug, and rosuvastatin, an HMG-CoA reductase inhibitor. This study evaluated the effect of multiple-dose ESL on the pharmacokinetic (PK) parameters of a single dose of rosuvastatin in healthy subjects. This was a Phase I, single-center, fixed-sequence, open-label study. Healthy subjects received two treatments, in sequence. Treatment A: a single 40mg oral dose of rosuvastatin on Day 1, followed by a washout period (Days 1-4); treatment B: titration of ESL (400-800mg once daily) on Days 5-18, followed by ESL 1200mg once daily on Days 19-35, with a single dose of rosuvastatin (40mg) on Day 32. Subjects then entered a 2-week follow-up period. Plasma concentrations of rosuvastatin were quantified for PK analyses. Safety and tolerability were assessed throughout the study. Thirty-three healthy subjects were enrolled and 30 completed the study. Mean rosuvastatin (standard deviation) t 1/2 was similar when rosuvastatin was used concomitantly with ESL and when it was used alone (26.5 [16.3]h, and 22.4 [9.5]h, respectively). The geometric least squares mean ratios (90% confidence intervals) of rosuvastatin exposure levels between rosuvastatin used concomitantly with ESL and rosuvastatin used alone were as follows: C max , 64.0% (55.9-73.3%); AUC (0-∞) , 63.0% (57.1-69.4%); and AUC (0-last) , 60.9% (55.2-67.1%). Concomitant use of ESL and rosuvastatin was generally well tolerated. Rosuvastatin exposure was 36-39% lower with steady-state administration of ESL, potentially due to reduced oral bioavailability of rosuvastatin. Consequently, when rosuvastatin is used with ESL, a rosuvastatin dose adjustment may be necessary if a clinically significant change in lipids is noted. Copyright © 2017. Published by Elsevier B.V.

No clinically meaningful pharmacokinetic interaction between the hepatitis C virus inhibitors elbasvir and grazoprevir and the oral contraceptives ethinyl estradiol and levonorgestrel.

PubMed

Marshall, William L; Feng, Hwa-Ping; Caro, Luzelena; Talaty, Jennifer; Guo, Zifang; Huang, Xiaobi; Panebianco, Deborah; Ma, Joanne; Mangin, Eric; O'Reilly, Terry E; Butterton, Joan R; Yeh, Wendy W

2017-05-01

Oral contraceptive pills (OCPs) are an important element of hepatitis C virus (HCV) treatment in women of childbearing potential. These studies evaluated the safety and pharmacokinetic interactions between elbasvir (EBR) and grazoprevir (GZR) and ethinyl estradiol/levonorgestrel (EE/LNG). Both studies were open-label, single-site, two-period, fixed-sequence, one-way interaction studies. In period 1, subjects received one tablet of EE/LNG (0.03 mg/0.15 mg). In period 2, subjects received EBR (50 mg once daily) for 13 days or GZR (200 mg once daily) for 10 days, with one tablet of EE/LNG on day 7 (GZR group) or 10 (EBR group). Each study enrolled 20 healthy, nonsmoking adult females. There was no clinically meaningful effect of multiple doses of EBR or GZR on the pharmacokinetics of EE or LNG. Geometric mean ratios (GMRs) for AUC 0-∞ and C max in the presence and absence of EBR were 1.01 and 1.10 for EE and 1.14 and 1.02 for LNG, with 90% confidence intervals (CIs) that were contained in the interval [0.80, 1.25]. Similarly, the AUC 0-∞ and C max GMRs in the presence and absence of GZR were 1.10 and 1.05 for EE and 1.23 and 0.93 for LNG, respectively. The 90% CIs for EE AUC 0-∞ and for EE and LNG C max were contained in the interval [0.80, 1.25]; however, the 90% CI for the LNG AUC 0-∞ [1.15, 1.32] slightly exceeded the upper bound. These results suggest that EBR/GZR can be co-administered to female patients with HCV of childbearing potential who are on OCPs to prevent pregnancy.

Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency

PubMed Central

Nilsson, A G; Marelli, C; Fitts, D; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Edén Engström, B; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Lennernäs, H; Skrtic, S; Johannsson, G

2014-01-01

Objective The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Design Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20–40 mg once daily and hydrocortisone 20–40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results In stage 1, patients had a median 1.5 (range, 1–9) intercurrent illness events with DR-HC and 1.0 (1–8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1–3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy. PMID:24944332

Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency.

PubMed

Nilsson, A G; Marelli, C; Fitts, D; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Engström, B Edén; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Lennernäs, H; Skrtic, S; Johannsson, G

2014-09-01

The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy. © 2014 The authors.

Daily consumption of foods and nutrients from institutional and home sources among young children attending two contrasting day-care centers in Guatemala City.

PubMed

Vossenaar, M; Jaramillo, P M; Soto-Méndez, M-J; Panday, B; Hamelinck, V; Bermúdez, O I; Doak, C M; Mathias, P; Solomons, N W

2012-12-01

Adequate nutrition is critical to child development and institutions such as day-care centers could potentially complement children's diets to achieve optimal daily intakes. The aim of the study was to describe the full-day diet of children, examining and contrasting the relative contribution of home-derived versus institutional energy and nutrient sources. The present comparison should be considered in the domain of a case-study format. The diets of 33, 3-6 y old children attending low-income day-care centers serving either 3 or a single meal were examined. The home-diet was assessed by means of 3 non-consecutive 24-hr recalls. Estimated energy and nutrient intakes at the centers and at home were assessed and related to Recommended Nutrient Intakes (RNI). Nutrient densities, critical densities and main sources of nutrients were computed. We observed that in children attending the day-care center serving three meals, home-foods contributed less than half the daily energy (47.7%) and between 29.9% and 53.5% of daily nutrients. In children receiving only lunch outside the home, energy contribution from the home was 83.9% and 304 kcal lower than for children receiving 3 meals. Furthermore, between 59.0% and 94.8% of daily nutrients were provided at home. Daily energy, nutrient intakes and nutrient densities were well above the nutrient requirements for this age group, and particularly high for vitamin A. The overall dietary variety was superior in the situation of greater contribution of home fare, but overall the nutrient density and adequacy of the aggregate intakes did not differ in any important manner.

Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol.

PubMed

Wiesinger, Herbert; Berse, Matthias; Klein, Stefan; Gschwend, Simone; Höchel, Joachim; Zollmann, Frank S; Schütt, Barbara

2015-12-01

The present study was conducted to investigate the influence of the strong CYP3A4 inhibitor ketoconazole (KTZ) on the pharmacokinetics of drospirenone (DRSP) administered in combination with ethinylestradiol (EE) or estradiol (E2). This was a randomized, multicentre, open label, one way crossover, fixed sequence study with two parallel treatment arms. A group sequential design allowed terminating the study for futility after first study cohort. About 50 healthy young women were randomized 1 : 1 to 'DRSP/EE' or 'DRSP/E2'. Subjects in the 'DRSP/EE' group received DRSP 3 mg/EE 0.02 mg (YAZ®, Bayer) once daily for 21 to 28 days followed by DRSP 3 mg/EE 0.02 mg once daily plus KTZ 200 mg twice daily for 10 days. Subjects in the 'DRSP/E2' group received DRSP 3 mg/E2 1.5 mg (research combination) once daily for 21 to 28 days followed by DRSP 3 mg/E2 1.5 mg once daily plus KTZ 200 mg twice daily for 10 days. Oral co-administration of DRSP/EE or DRSP/E2 and KTZ resulted in an increase in DRSP exposure (AUC(0,24 h)) in both treatment groups: DRSP/EE group: 2.68-fold DRSP increase (90% CI 2.44, 2.95); DRSP/E2 group: 2.30-fold DRSP increase (90% CI 2.08, 2.54). EE and estrone (metabolite of E2) exposures were increased ~1.4-fold whereas E2 exposure was largely unaffected by KTZ co-administration. A moderate pharmacokinetic drug-drug interaction between DRSP and KTZ was demonstrated in this study. No relevant changes of medical concern were detected in the safety data collected in this study. © 2015 The British Pharmacological Society.

Physical activity in subjects with multiple sclerosis with focus on gender differences: a survey

PubMed Central

2014-01-01

Background There is increasing research that examines gender-issues in multiple sclerosis (MS), but little focus has been placed on gender-issues regarding physical activity. The aim of the present study was to describe levels of physical activity, self-efficacy for physical activity, fall-related self-efficacy, social support for physical activity, fatigue levels and the impact of MS on daily life, in addition to investigating gender differences. Methods The sample for this cross-sectional cohort study consisted of 287 (84 men; 29.3%) adults with MS recruited from the Swedish Multiple Sclerosis Registry. A questionnaire was sent to the subjects consisting of the self-administrated measurements: Physical Activity Disability Survey – Revised, Exercise Self-Efficacy Scale, Falls- Efficacy Scale (Swedish version), Social Influences on Physical Activity, Fatigue Severity Scale and Multiple Sclerosis Impact Scale. Response rate was 58.2%. Results Men were less physically active, had lower self-efficacy for physical activity and lower fall-related self-efficacy than women. This was explained by men being more physically affected by the disease. Men also received less social support for physical activity from family members. The level of fatigue and psychological consequences of the disease were similar between the genders in the total sample, but subgroups of women with moderate MS and relapsing remitting MS experienced more fatigue than men. Conclusions Men were less physically active, probably a result of being more physically affected by the disease. Men being more physically affected explained most of the gender differences found in this study. However, the number of men in the subgroup analyses was small and more research is needed. A gender perspective should be considered in strategies for promoting physical activity in subjects with MS, e.g. men may need more support to be physically active. PMID:24612446

Physical activity in subjects with multiple sclerosis with focus on gender differences: a survey.

PubMed

Anens, Elisabeth; Emtner, Margareta; Zetterberg, Lena; Hellström, Karin

2014-03-10

There is increasing research that examines gender-issues in multiple sclerosis (MS), but little focus has been placed on gender-issues regarding physical activity. The aim of the present study was to describe levels of physical activity, self-efficacy for physical activity, fall-related self-efficacy, social support for physical activity, fatigue levels and the impact of MS on daily life, in addition to investigating gender differences. The sample for this cross-sectional cohort study consisted of 287 (84 men; 29.3%) adults with MS recruited from the Swedish Multiple Sclerosis Registry. A questionnaire was sent to the subjects consisting of the self-administrated measurements: Physical Activity Disability Survey - Revised, Exercise Self-Efficacy Scale, Falls-Efficacy Scale (Swedish version), Social Influences on Physical Activity, Fatigue Severity Scale and Multiple Sclerosis Impact Scale. Response rate was 58.2%. Men were less physically active, had lower self-efficacy for physical activity and lower fall-related self-efficacy than women. This was explained by men being more physically affected by the disease. Men also received less social support for physical activity from family members. The level of fatigue and psychological consequences of the disease were similar between the genders in the total sample, but subgroups of women with moderate MS and relapsing remitting MS experienced more fatigue than men. Men were less physically active, probably a result of being more physically affected by the disease. Men being more physically affected explained most of the gender differences found in this study. However, the number of men in the subgroup analyses was small and more research is needed. A gender perspective should be considered in strategies for promoting physical activity in subjects with MS, e.g. men may need more support to be physically active.

Determination of osteoporosis risk factors using a multiple logistic regression model in postmenopausal Turkish women.

PubMed

Akkus, Zeki; Camdeviren, Handan; Celik, Fatma; Gur, Ali; Nas, Kemal

2005-09-01

To determine the risk factors of osteoporosis using a multiple binary logistic regression method and to assess the risk variables for osteoporosis, which is a major and growing health problem in many countries. We presented a case-control study, consisting of 126 postmenopausal healthy women as control group and 225 postmenopausal osteoporotic women as the case group. The study was carried out in the Department of Physical Medicine and Rehabilitation, Dicle University, Diyarbakir, Turkey between 1999-2002. The data from the 351 participants were collected using a standard questionnaire that contains 43 variables. A multiple logistic regression model was then used to evaluate the data and to find the best regression model. We classified 80.1% (281/351) of the participants using the regression model. Furthermore, the specificity value of the model was 67% (84/126) of the control group while the sensitivity value was 88% (197/225) of the case group. We found the distribution of residual values standardized for final model to be exponential using the Kolmogorow-Smirnow test (p=0.193). The receiver operating characteristic curve was found successful to predict patients with risk for osteoporosis. This study suggests that low levels of dietary calcium intake, physical activity, education, and longer duration of menopause are independent predictors of the risk of low bone density in our population. Adequate dietary calcium intake in combination with maintaining a daily physical activity, increasing educational level, decreasing birth rate, and duration of breast-feeding may contribute to healthy bones and play a role in practical prevention of osteoporosis in Southeast Anatolia. In addition, the findings of the present study indicate that the use of multivariate statistical method as a multiple logistic regression in osteoporosis, which maybe influenced by many variables, is better than univariate statistical evaluation.

Shorter-Course Whole-Brain Radiotherapy for Brain Metastases in Elderly Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk, E-mail: rades.dirk@gmx.net; Department of Radiation Oncology, University Hospital Hamburg-Eppendorf, Hamburg; Evers, Jasmin N.

2011-11-15

Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 Multiplication-Sign 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 Multiplication-Sign 3 Gy with 5 Multiplication-Sign 4 Gy in elderly patients ({>=}65 years). Methods and Materials: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 Multiplication-Sign 3 Gy were compared with 162 patientsmore » receiving 5 Multiplication-Sign 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: The 6-month overall survival rates were 29% after 5 Multiplication-Sign 4 Gy and 21% after 10 Multiplication-Sign 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS {>=} 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS {>=} 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). Conclusions: Shorter-course WBRT with 5 Multiplication-Sign 4 Gy was not inferior to 10 Multiplication-Sign 3 Gy with respect to overall survival or local control in elderly patients. 5 Multiplication-Sign 4 Gy appears preferable for the majority of these patients.« less

Lunisolar tidal waves, geomagnetic activity and epilepsy in the light of multivariate coherence.

PubMed

Mikulecky, M; Moravcikova, C; Czanner, S

1996-08-01

The computed daily values of lunisolar tidal waves, the observed daily values of Ap index, a measure of the planetary geomagnetic activity, and the daily numbers of patients with epileptic attacks for a group of 28 neurology patients between 1987 and 1992 were analyzed by common, multiple and partial cross-spectral analysis to search for relationships between periodicities in these time series. Significant common and multiple coherence between them was found for rhythms with a period length over 3-4 months, in agreement with seasonal variations of all three variables. If, however, the coherence between tides and epilepsy was studied excluding the influence of geomagnetism, two joint infradian periodicities with period lengths of 8.5 and 10.7 days became significant. On the other hand, there were no joint rhythms for geomagnetism and epilepsy when the influence of tidal waves was excluded. The result suggests a more primary role of gravitation, compared with geomagnetism, in the multivariate process studied.

Stability and change in sustainability of daily routines and social networks in families of children with profound intellectual and multiple disabilities.

PubMed

Wilder, Jenny; Granlund, Mats

2015-03-01

Children with profound intellectual and multiple disabilities (PIMD) demand intense family accommodations from birth and onwards. This study used an exploratory and qualitative study design to investigate stability and change in sustainability of daily routines and social networks of Swedish families of children with PIMD. Eight families participated over two years in eco-cultural family interviews and social networks interviews collected at home visits. Data were analyzed descriptively and by manifest contents analysis. Results showed variations in sustainability of daily routines over time across families. The sustainability was linked to fathers' involvement, couples' connectedness and emotional support. Stability and change of social networks were characterized by low overlap between the child and family networks, the children's communicative dependency and low density of able communication partners. The results indicate that patterns of stability and change were linked both to family resources and child characteristics. © 2014 John Wiley & Sons Ltd.

Using Multiple Metrics to Analyze Trends and Sensitivity of Climate Variability in New York City

NASA Astrophysics Data System (ADS)

Huang, J.; Towey, K.; Booth, J. F.; Baez, S. D.

2017-12-01

As the overall temperature of Earth continues to warm, changes in the Earth's climate are being observed through extreme weather events, such as heavy precipitation events and heat waves. This study examines the daily precipitation and temperature record of the greater New York City region during the 1979-2014 period. Daily station observations from three greater New York City airports: John F. Kennedy (JFK), LaGuardia (LGA) and Newark (EWR), are used in this study. Multiple statistical metrics are used in this study to analyze trends and variability in temperature and precipitation in the greater New York City region. The temperature climatology reveals a distinct seasonal cycle, while the precipitation climatology exhibits greater annual variability. Two types of thresholds are used to examine the variability of extreme events: extreme threshold and daily anomaly threshold. The extreme threshold indicates how the strength of the overall maximum is changing whereas the daily anomaly threshold indicates if the strength of the daily maximum is changing over time. We observed an increase in the frequency of anomalous daily precipitation events over the last 36 years, with the greatest frequency occurring in 2011. The most extreme precipitation events occur during the months of late summer through early fall, with approximately four expected extreme events occurring per year during the summer and fall. For temperature, the greatest frequency and variation in temperature anomalies occur during winter and spring. In addition, temperature variance is also analyzed to determine if there is greater day-to-day temperature variability today than in the past.

Service workers' chain reactions to daily customer mistreatment: Behavioral linkages, mechanisms, and boundary conditions.

PubMed

Chi, Nai-Wen; Yang, Jixia; Lin, Chia-Ying

2018-01-01

Drawing on the stressor-emotion model, we examine how customer mistreatment can evoke service workers' passive forms of deviant behaviors (i.e., work withdrawal behavior [WWB]) and negative impacts on their home life (i.e., work-family conflict [WFC]), and whether individuals' core self-evaluations and customer service training can buffer the negative effects of customer mistreatment. Using the experience sampling method, we collect daily data from 77 customer service employees for 10 consecutive working days, yielding 546 valid daily responses. The results show that daily customer mistreatment increases service workers' daily WWB and WFC through negative emotions. Furthermore, employees with high core self-evaluations and employees who received customer service training are less likely to experience negative emotions when faced with customer mistreatment, and thus are less likely to engage in WWB or provoke WFC. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Use of inpatient continuous passive motion versus no CPM in computer-assisted total knee arthroplasty.

PubMed

Alkire, Martha R; Swank, Michael L

2010-01-01

Continuous passive motion (CPM) has shown positive effects on tissue healing, edema, hemarthrosis, and joint function (L. Brosseau et al., 2004). CPM has also been shown to increase short-term early flexion and decrease length of stay (LOS) ( L. Brosseau et al., 2004; C. M. Chiarello, C. M. S. Gundersen, & T. O'Halloran, 2004). The benefits of CPM for the population of patients undergoing computer-assisted total knee arthroplasty (TKA) have not been examined. The primary objective of this study was to determine whether the use of CPM following computer-assisted TKA resulted in differences in range of motion, edema/drainage, functional ability, and pain. This was an experimental, prospective, randomized study of patients undergoing unilateral, computer-assisted TKA. The experimental group received CPM thrice daily and physical therapy (PT) twice daily during their hospitalization. The control group received PT twice daily and no CPM during the hospital stay. Both groups received PT after discharge. Measurement included Knee Society scores, Western Ontario McMaster Osteoarthritis Index values, range of motion, knee circumference, and HemoVac drainage. Data were collected at various intervals from preoperatively through 3 months. Although the control group was found to be higher functioning preoperatively, there was no statistically significant difference in flexion, edema or drainage, function, or pain between groups through the 3-month study period.

Reduction in morbidity after iliac crest bone harvesting: the concept of preemptive analgesia.

PubMed

Hoard, M A; Bill, T J; Campbell, R L

1998-09-01

The technique of autologous iliac crest bone grafting is an important aspect in the treatment of patients with cleft lip, cleft palate, and other craniofacial disorders. In patients with cleft lip and palate, the alveolar bone graft creates a continuous maxillary arch, closes the oronasal fistula, provides bony support for facial soft tissue and teeth, and facilitates orthodontic movement of teeth. The anatomic and physiologic benefits of this and similar autologous bone graft procedures are apparent. However, pain at the donor site represents a significant source of postoperative morbidity. This study was conducted to evaluate postoperative pain and the ability to perform activities of daily living after bupivacaine infiltration to iliac crest donor sites. Thirty-four alveolar bone graft patients (18 females, 16 males) treated at two teaching hospitals were included in the study. Eleven of the patients received intraoperative bupivacaine at the iliac donor site and 23 did not. A questionnaire was returned by all participants, and telephone follow-up was obtained. Responses to postoperative pain, time period to ambulation, and ability to perform activities of daily living were evaluated. Patients who received postoperative bupivacaine experienced delayed onset of postoperative pain, earlier ambulation, and were able to return to normal daily activity in a shorter period of time than those patients who received no local anesthesia. The concept of preemptive analgesia and its application to craniofacial surgery is discussed.

Towards the development of a multimodel hydrological ensemble prediction system for La Mojana, Colombia

NASA Astrophysics Data System (ADS)

Brochero, D.; Peña, J.; Anctil, F.; Boucher, M. A.; Nogales, J.; Reyes, N.

2016-12-01

The impacts of floods in Colombia during 2010 and 2011 as a result of ENSO in its cold phase (La Niña) marked a milestone in Colombian politics. In La Mojana region the balance was around 100,000 homeless and 3 km2 of flooded crops. We model the upstream basin of La Mojana (3600 km2 and a mean annual precipitation from 1000mm in valleys to 4500 mm in mountains). A forecasting system of at least three days in advance was judged prudent. This basin receives an streamflow highly regulated by multiple reservoirs that we model with a recurrent neural networks from 1 to 3-days ahead. For hydrological modeling purposes we use the GR4J, HBV, and SIMHYD models, records of daily precipitation, temperature, and streamflows, and 110 prediction scenarios of precipitation and temperature from Canada, USA, Brazil, and Europe extracted from the TIGGE database (MEPS). Calibration period is between January 2004 and August 2011. Validation from September to December 2011, taking as meteorological input the MEPS. We analised four alternative for the 3-day Hydrological Ensemble Prediction System (HEPS) Calibration: 1) only the GR4J model and observed values, 2). as 1 but HBV and SIMHYD are included, 3). Simultaneous optimization of the three hydrological models based on the reliability maximisation and the CRPS minimisation using the multiobjective calibration, observed and forecasted temperature and precipitation from the MEPS and, 4). as 3 but adding the daily streamflow data assimilation. Results show that the use of multiple hydrological models is clearly advantageous but even more performing the simultaneous optimization of hydrological models in the probabilistic context directly. The results evolution of the MAE on the reliability diagram (MAE-RD) are 43%, 27%, 17% and 15% respectively for the four alternatives. Regarding CRPS, MAE results show that the probabilistic prediction improves the deterministic estimate based on the daily mean HEPS scenario, despite the improvement in reliability is not necessarily reflected in the CRPS for the four alternatives: 4.3, 3.06 , 9.98, and 3.94, values that also accompany the mean scenario Nash-Sutcliffe of 0.93, 0.96, 0.51, and 0.93 respectively. In conclusion it shows that alternative 4 reached a good compromise between the deterministic and probabilistic performance (NS=0.93 and MAERD = 15%).

[Factors related to the demand of caregivers for institutionalization of disabled persons living at home].

PubMed

Tanikake, Chisato

2005-03-01

Recently, there has been an increase in the number of caregivers who are demanding institutionalization of the disabled, despite having taken care of them at home since their birth. It is important to clarify the background of this demand in order to help develop plans aimed at socially supporting the caregivers. This study was aimed at elucidating the factors related to demands of caregivers to have disabled persons living at home institutionalized. To caregivers of 410 home-living disabled persons, we handed out and collected questionnaires asking for the following information: age of the disabled persons and their caregivers, severity of the disability, status and level of manageability of the caregivers, and the place where the caregivers wanted the disabled to live in the future. The demand for institutionalization of the disabled and the attributes of the responders were analyzed by multiple logistic regression. From the responses of 297 people who replied to the questions, univariate analysis revealed that the demand for institutionalization significantly correlated with the labels of "severe" in the mental disability certificate, "incapable of conversation" according to the Office of Population Censuses and Surveys (OPCS) scale, "severe disability" in Oshima's classification and "unfit" and "unable to give daily care." The results analyzed by multiple logistic regression revealed that older caregivers had a significantly higher odds ratio (18.3 for those in their 40s and 37.2 for those in their 50s), indicating a strong correlation between the demand for institutionalization and the age of the caregivers. According to the mental disability certificate, the odds ratio of those with "A" was 5.0 relative to "other than A," while the odds ratio was 3.8 for those "unable to give care" against "able to give care," in both cases statistically significant. As for suffering in daily life, a majority of the caregivers aged 50 years or older claimed "a limit to home caring" and "aging". Regarding the shortage of public welfare services, a large percentage pointed out the inconveniences of emergency short stay, short stay, day care, and bathing services. The factors related to demand for institutionalization of disabled care receivers at home were aging of the caregivers, incapability of giving daily care, and severe mental impairment. The age of the caregivers was identified as an explicit factor.

Association between Exposure to Smartphones and Ocular Health in Adolescents.

PubMed

Kim, Joowon; Hwang, Yunji; Kang, Seungheon; Kim, Minhye; Kim, Tae-Shin; Kim, Jay; Seo, Jeongmin; Ahn, Hyojeong; Yoon, Sungjoon; Yun, Jun Pil; Lee, Yae Lim; Ham, Hyunsoo; Yu, Hyeong Gon; Park, Sue K

2016-08-01

Smartphone use has dramatically increased in recent years. Smartphones may have adverse health effects, particularly on the eyes, because users stare at the screen for a much longer time than they do with ordinary mobile phones. The objective of this study was to elucidate the relationship between smartphone use and ocular symptoms among adolescents. Information on smartphone use and ocular symptoms (blurring, redness, visual disturbance, secretion, inflammation, lacrimation and dryness) related to eye fatigue and strain from 715 adolescent subjects from three cities in Korea was obtained using a structured questionnaire. Ocular health was scored using number of ocular symptoms. Odds ratios (ORs), 95% confidence intervals (95% CIs) and p-values for ocular symptoms were calculated with binomial and multinomial logistic regression models. Higher prevalence rates for ocular symptoms were observed in groups with greater exposure to smartphones (p < 0.05). Longer daily smartphone use was associated with a higher likelihood of having multiple ocular symptoms (5-7 symptoms out of 7 symptoms; p = 0.005). Excessive/intermittent use (>2 hours daily and ≤2 hours continuously) and excessive/persistent use (>2 hours daily and >2 hours continuously) compared to shorter use (<2 hours daily) were associated with multiple ocular symptoms (OR 2.18, 95% CI 1.09-4.39; OR 2.26, 95% CI 1.11-4.57, respectively). A higher lifetime exposure to smartphones was associated with a higher likelihood of having multiple ocular symptoms (OR 3.05, 95% CI 1.51-6.19; p = 0.001). Increasing exposure to smartphones can have a negative impact on ocular health in adolescents.

Donepezil dosing strategies: pharmacokinetic considerations.

PubMed

Gomolin, Irving H; Smith, Candace; Jeitner, Thomas M

2011-10-01

Donepezil (Aricept) is a cholinesterase inhibitor approved for the treatment of Alzheimer's disease. Immediate release formulations of 5- and 10-mg tablets were approved by the Food and Drug Administration in the United States in 1996. In July 2010, the Food and Drug Administration approved a 23-mg sustained release (SR) formulation. The SR formulation may provide additional benefit to patients receiving 10 mg daily but the incidence of adverse reactions is increased. We derived plasma concentration profiles for higher dose immediate-release formulations (15 mg once daily, 10 mg twice daily, and 20 mg once daily) and for the profile anticipated to result from the 23-mg SR formulation. Our model predicts similar steady-state concentration profiles for 10 mg twice daily, 20 mg once daily, and 23 mg SR once daily. This provides the theoretical basis for incremental immediate release dose escalation to minimize the emergence of adverse reactions and the potential to offer a cost-effective alternative to the SR formulation with currently approved generic immediate release formulations. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

Young adolescents who respond to an inulin-type fructan substantially increase total absorbed calcium and daily calcium accretion to the skeleton

USDA-ARS?s Scientific Manuscript database

Calcium absorption and whole-body bone mineral content are greater in young adolescents who receive 8 g/d of Synergy, a mixture of inulin-type fructans (ITF), compared with those who received a maltodextrin control. Not all adolescents responded to this intervention, however. We evaluated 32 respond...

Disulfiram-induced acute organic brain syndrome.

PubMed

Kump, J G; Flaten, P A; Greenlaw, C W

1979-08-01

Reversible acute organic brain syndrome is described in a patient receiving disulfiram, 250 mg daily. Slowing of the electroencephalogram (3 to 4 cycles per second) in the occipital region resolved ten days after discontinuation of disulfiram. Acute organic brain syndrome induced by disulfiram is not rare but is often not correlated, and it should always be considered a possibility in patients receiving disulfiram therapy.

Effects of Physalis peruviana L on Toxicity and Lung Cancer Induction by Nicotine Derived Nitrosamine Ketone in Rats.

PubMed

El-Kenawy, Ayman El-Meghawry; Elshama, Said Said; Osman, Hosam-Eldin Hussein

2015-01-01

Nicotine-derived nitrosamine ketone (NNK) is considered a key tobacco smoke carcinogen inducing lung tumors. Physalis peruviana L (harankash) is considered one plant with marked health benefits. This study aimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by using pulmonary histopathological, immunohistochemical and DNA flow cytometric analyses. Sixty adult male rats were divided into four groups, each consisting of fifteen animals. The first group received saline, the second received two successive toxic doses of NNK only while the third received two successive toxic doses of NNK with a single daily dose of Physalis peruviana L. The fourth group received a single daily dose of Physalis peruviana L only. Toxic doses of NNK induced hyperplasia and adenocarcinoma in the lung and positive immunoreactivity for Ki-67 and p53 staining with disturbance of the lung DNA content. Administration of Physalis peruviana L with NNK led to a mild pulmonary hyperplasia and weak expression of Ki-67 and p53 with an improvement in the lung DNA content. Physalis peruviana L may protect against NNK induced lung carcinogenesis due to its antioxidant and anti-proliferative effects.

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors.

PubMed

Gladman, Dafna; Rigby, William; Azevedo, Valderilio F; Behrens, Frank; Blanco, Ricardo; Kaszuba, Andrzej; Kudlacz, Elizabeth; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

2017-10-19

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis. At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib. In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).

Modifications of the One-More-Than Technique: A Comparison of Two Strategies for Teaching Purchasing Skills to Students with Intellectual Disability in Taiwan

ERIC Educational Resources Information Center

Hsu, Guo-Liang; Tang, Jung-Chang; Hwang, Wu-Yuin; Li, Yung-Chang; Hwang, Wu-Yuin; Li, Yung-Chang; Hung, Jung-Chao; Wei, Chun-Hwa

2016-01-01

The demands of money-counting skills potentially limit individuals with intellectual disability (ID) to master the one-more-than technique, particularly in Taiwan, which requires high daily minimum living expense for supporting an individual's daily life. Employing a multiple treatment design across price ranges and settings, this study compared…

Antihypertensive Effects of Hydroalcoholic Extract of Crataegus Azarolus Subspecies Aronia Fruit in Rats with Renovascular Hypertension: An Experimental Mechanistic Study

PubMed Central

Haydari, Mohammad Reza; Panjeshahin, Mohammad Reza; Mashghoolozekr, Elaheh; Nekooeian, Ali Akbar

2017-01-01

Background: Hawthorn species decreases blood pressure and relaxes precontracted vessels. This study aimed at examining the antihypertensive effect and related mechanisms of hydroalcoholic extract of Crataegus azarolus subspecies aronia fruit in rats with renovascular hypertension. Methods: Six groups of male Sprague-Dawley rats, each containing 6 to 8 rats, were studied. The groups comprised of one sham group and 5 renal artery-clipped groups. The sham group received vehicle (distilled water 0.5 ml/day) and the renal artery-clipped groups received vehicle or the extract at 5, 10, 20 or 30 mg/kg/day. Oral vehicle or extract was administered daily for 4 weeks following sham-operation or induction of hypertension. Systolic blood pressure and heart rate were measured weekly. Isolated aorta study was performed by last week and serum superoxide dismutase and glutathione reductase were measured. The findings were analyzed using one-way analysis of variance and Duncan’s multiple range tests at P≤0.05 using SigmaStat software. Results: The data obtained after 4 weeks of treatment showed that the renal artery-clipped group receiving vehicle had significantly higher systolic blood pressure (P=0.002) and phenylephrine maximal response (P=0.01); and lower acetylcholine maximal response (P=0.01), serum superoxide dismutase (P=0.006) and serum glutathione reductase (P=0.006) than those of the sham group. The renal artery-clipped group receiving extract had significantly lower systolic blood pressure (P=0.03) and phenylephrine maximal response (P=0.01); and significantly higher acetylcholine maximal response (P=0.01), serum superoxide dismutase (P=0.015), and serum glutathione reductase (P=0.015) than those of the renal artery-clipped group receiving vehicle. Conclusion: Our findings show that the hydroalcoholic extract of Crataegus azarolus subspecies aronia fruit has antihypertensive effects, which may be partly due to antioxidant and nitric oxide releasing effects. PMID:28533575

Antihypertensive Effects of Hydroalcoholic Extract of Crataegus Azarolus Subspecies Aronia Fruit in Rats with Renovascular Hypertension: An Experimental Mechanistic Study.

PubMed

Haydari, Mohammad Reza; Panjeshahin, Mohammad Reza; Mashghoolozekr, Elaheh; Nekooeian, Ali Akbar

2017-05-01

Hawthorn species decreases blood pressure and relaxes precontracted vessels. This study aimed at examining the antihypertensive effect and related mechanisms of hydroalcoholic extract of Crataegus azarolus subspecies aronia fruit in rats with renovascular hypertension. Six groups of male Sprague-Dawley rats, each containing 6 to 8 rats, were studied. The groups comprised of one sham group and 5 renal artery-clipped groups. The sham group received vehicle (distilled water 0.5 ml/day) and the renal artery-clipped groups received vehicle or the extract at 5, 10, 20 or 30 mg/kg/day. Oral vehicle or extract was administered daily for 4 weeks following sham-operation or induction of hypertension. Systolic blood pressure and heart rate were measured weekly. Isolated aorta study was performed by last week and serum superoxide dismutase and glutathione reductase were measured. The findings were analyzed using one-way analysis of variance and Duncan's multiple range tests at P≤0.05 using SigmaStat software. The data obtained after 4 weeks of treatment showed that the renal artery-clipped group receiving vehicle had significantly higher systolic blood pressure (P=0.002) and phenylephrine maximal response (P=0.01); and lower acetylcholine maximal response (P=0.01), serum superoxide dismutase (P=0.006) and serum glutathione reductase (P=0.006) than those of the sham group. The renal artery-clipped group receiving extract had significantly lower systolic blood pressure (P=0.03) and phenylephrine maximal response (P=0.01); and significantly higher acetylcholine maximal response (P=0.01), serum superoxide dismutase (P=0.015), and serum glutathione reductase (P=0.015) than those of the renal artery-clipped group receiving vehicle. Our findings show that the hydroalcoholic extract of Crataegus azarolus subspecies aronia fruit has antihypertensive effects, which may be partly due to antioxidant and nitric oxide releasing effects.

Launch Control System Master Console Event Message Reduction

NASA Technical Reports Server (NTRS)

Nguyen, Uyen

2014-01-01

System monitoring and control (SMC) message browsers receive so many messages daily that operators do not need to see. Important messages are often mixed up among the less important ones. My job is to reduce the messages displayed in the message browser so that warning and emergency messages can be seen easily and therefore, responded promptly. There are multiple methods to achieve this. Firstly, duplicate messages should not appear many times in the message browser. Instead, the message should appear only once but with a number that counts the times that it appears. This method is called duplicate message suppression. Secondly, messages that update the most recent state (e.g. up/down) of a component should replace the old-state messages. This method is called state based message correlation. Thirdly, messages that display "normal" alarm level should be suppressed unless it's a response to an operator action. In addition to message reduction, I also work on correcting the severity level and text formats on messages.

Complicated lichenoid drug eruption.

PubMed

Armour, Katherine; Lowe, Patricia

2005-02-01

We report a case of severe lichenoid drug eruption with multiple possible causative agents. A hepatitis C-positive male presented with a short history of painful erosions of the vermilion, lichenoid lesions on the buccal mucosa and glans penis, and erosions and lichenification of the scrotum. In addition, he had a pruritic polymorphic eruption over the scalp, trunk and limbs, comprising psoriasiform and eczematous lesions. He had received combination therapy of pegylated interferon-alpha-2a and ribavirin, along with granulocyte colony-stimulating factor for interferon-induced leucopenia, and propranolol for portal hypertension. The former three agents were ceased 3 weeks prior to presentation, but he remained on propranolol at the initial dermatology consultation. The polymorphous clinical picture was consistent with lichenoid drug eruption, which was confirmed on histology. The papulosquamous eruption responded quickly to 2 weeks of oral prednisone 25 mg daily, which was tapered to 1 mg over 3 months and then ceased. The mucosal lesions were slow to improve and required the addition of tacrolimus 0.03% solution t.d.s. for complete resolution.

Cholestyramine induced hyperchloremic metabolic acidosis.

PubMed

Eaves, E R; Korman, M G

1984-10-01

The first reported case, in an adult, of cholestyramine induced hyperchloremic metabolic acidosis is a 70 year old female with a two year history of primary biliary cirrhosis confirmed by histologic and immunologic criteria. After taking cholestyramine II sachets twice daily for two months she presented with lethargy, confusion and drowsiness. Examination revealed confusion, jaundice, signs of chronic liver disease, portal hypertension and hepatic encephalopathy. Laboratory investigations confirmed a metabolic acidosis (pH 7.15) and hyperchloremia. Multiple cultures failed to reveal sepsis and a urinary pH of 4.85 together with tests of renal acidification, excluded renal tubular acidosis. She received 600 mEq of sodium bicarbonate intravenously over 36 hours by which time her mentation, electrolytes and pH were normal. It is presumed that her hyperchloremic metabolic acidosis was secondary to cholestyramine because of the similarity to pediatric reports; the rapid and lasting response to intravenous sodium bicarbonate; the absence of another etiology; normal serum potassium, chloride and bicarbonate despite continued spironolactone therapy after recovery.

Sustained complete response of hepatocellular carcinoma with portal vein tumor thrombus following discontinuation of sorafenib: A case report

PubMed Central

SHIOZAWA, KAZUE; WATANABE, MANABU; IKEHARA, TAKASHI; MATSUKIYO, YASUSHI; KOGAME, MICHIO; KANAYAMA, MASAHIRO; MATSUI, TEPPEI; KIKUCHI, YOSHINORI; ISHII, KOJI; IGARASHI, YOSHINORI; SUMINO, YASUKIYO

2014-01-01

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated mortality worldwide. No effective treatment has been established for unresectable advanced HCC, and the prognosis is poor. Sorafenib is an oral multi-targeted tyrosine kinase inhibitor for unresectable advanced HCC that significantly improves progression-free and overall survival. However, in the two large phase III clinical trials (the SHARP and Asia-Pacific trials), no cases of complete response (CR) were reported. The present study reports the case of a 68-year-old male with hepatitis C virus-related cirrhosis and multiple recurrent HCCs, with a tumor thrombus of the third portal vein following resection. The patient received 400 mg once daily (half the standard dose) of sorafenib for two years and achieved a CR. At the most recent follow-up examination at one year after the cessation of treatment, the patient was observed to be in remission without clinical or imaging evidence of disease recurrence. PMID:24348819

A new model for antisperm autoimmunity in guine pigs.

PubMed

Mazzolli, A B; Bustuoabad, O D; Barrera, C; Mancini, R E

1976-01-01

Adult outbread male guinea pigs were autoimmunized without adjuvant. Homogenates were prepared with one of their own testes previously submitted "in vivo" and "in vitro" to thermal injury. Animals received a single or daily repeated intradermal injection without added adjuvant, in one or different skin sites. Guinea pigs daily sensitized in the same site during 30 days showed the presence of: a) dermal granuloma at the site of injection; b) several foci of typical allergic orchitis; c) delayed hypersensitivity detected by inhibition of macrophage migration; d) moderate titres of spermagglutinins and negligible levels of hemagglutinating antibodies. Guinea pigs receiving a single dose in one site only developed delayed hypersensitivity. Animals daily sensitized with the same dose of altered antigen in different sites, or with normal testis antigen either in one or different sites, showed negative results. The correlation among testicular lesion, dermal granuloma and cellular immunity is discussed. It is concluded that testis autosensitization is obtained in the absence of added adjuvant provided that a thermally injured gonad used as antigen is repeatedly injected in the same site.

Effect of low-level laser therapy on dental root cementum remodeling in rats.

PubMed

Alsulaimani, M; Doschak, M; Dederich, D; Flores-Mir, C

2015-05-01

To investigate the amount of the cementum layer formed over the rat's dental root surfaces by daily application of low-level laser therapy (LLLT) for 2 weeks. Twelve female Sprague-Dawley (SD) rats were divided into two groups: six rats received daily LLLT (Ga-Al-As, 830 nm), and six rats received no treatment (control). The treatment lasted 2 weeks. In vivo Micro-CT imaging analyzed the root's hard tissue volumetric changes. The cementum thickness was evaluated histologically. Total cementum thicknesses in the LLLT group increased significantly (p = 0.015) compared to the control group. This significant increase in the cementum thickness, verified histologically, was not detectable during in vivo Micro-CT imaging, which showed no significant difference between the groups regarding the root hard tissues volumetric changes over the 2-week evaluation period. Two weeks of daily application of LLLT significantly increased rat's dental root cementum thickness as determined histologically. However, in vivo Micro-CT imaging failed to accurately reveal this cementum growth as it was not possible to differentiate dentinal changes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Relationships between Weather-Related Factors and Daily Outdoor Physical Activity Counts on an Urban Greenway

PubMed Central

Wolff, Dana; Fitzhugh, Eugene C.

2011-01-01

The purpose of this study was to examine relationships between weather and outdoor physical activity (PA). An online weather source was used to obtain daily max temperature [DMT], precipitation, and wind speed. An infra-red trail counter provided data on daily trail use along a greenway, over a 2-year period. Multiple regression analysis was used to examine associations between PA and weather, while controlling for day of the week and month of the year. The overall regression model explained 77.0% of the variance in daily PA (p < 0.001). DMT (b = 10.5), max temp-squared (b = −4.0), precipitation (b = −70.0), and max wind speed (b = 1.9) contributed significantly. Conclusion: Aggregated daily data can detect relationships between weather and outdoor PA. PMID:21556205

Radio Meteors Observations Techniques at RI NAO

NASA Astrophysics Data System (ADS)

Vovk, Vasyl; Kaliuzhnyi, Mykola

2016-07-01

The Solar system is inhabited with large number of celestial bodies. Some of them are well studied, such as planets and vast majority of big asteroids and comets. There is one group of objects which has received little attention. That is meteoroids with related to them meteors. Nowadays enough low-technology high-efficiency radio-technical solutions are appeared which allow to observe meteors daily. At RI NAO three methodologies for meteor observation are developed: single-station method using FM-receiver, correlation method using FM-receiver and Internet resources, and single-station method using low-cost SDR-receiver.

Effect of intermittent versus daily calorie restriction on changes in weight and patient reported outcomes in people with multiple sclerosis

USDA-ARS?s Scientific Manuscript database

An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding stud...

Creatively Encountering Languages in Caregiving and in the Early Childhood Classroom

ERIC Educational Resources Information Center

Madera, Piña

2015-01-01

For years, research has shown that language learning at an early age has great benefits. Most recently, a May 2015 study published in "Science Daily" suggests that exposure to multiple languages in childhood produces better communicators ("Children exposed to multiple languages"). A 2014 study in Singapore showed that infants…

Mexican American Adolescents' Profiles of Risk and Mental Health: A Person-Centered Longitudinal Approach

ERIC Educational Resources Information Center

Zeiders, Katharine H.; Roosa, Mark W.; Knight, George P.; Gonzales, Nancy A.

2013-01-01

Although Mexican American adolescents experience multiple risk factors in their daily lives, most research examines the influences of risk factors on adjustment independently, ignoring the additive and interactive effects of multiple risk factors. Guided by a person-centered perspective and utilizing latent profile analysis, this study identified…

Teachers Little Helper: Multi-Math-Coach

ERIC Educational Resources Information Center

Ebner, Martin; Schön, Martin; Taraghi, Behnam; Steyre, Michael

2013-01-01

Individual learning is out of sync with the elements of a curricula and the daily program of a teacher. At a time when multidigit multiplication methods are taught, many children are not perfectly performing the basic multiplication table. Teachers organize settings for learning and they usually have no time to give an individual feedback to every…

Intensive (Daily) Behavior Therapy for School Refusal: A Multiple Baseline Case Series

ERIC Educational Resources Information Center

Tolin, David F.; Whiting, Sara; Maltby, Nicholas; Diefenbach, Gretchen J.; Lothstein, Mary Anne; Hardcastle, Surrey; Catalano, Amy; Gray, Krista

2009-01-01

The following multiple baseline case series examines school refusal behavior in 4 male adolescents. School refusal symptom presentation was ascertained utilizing a functional analysis from the School Refusal Assessment Scale (Kearney, 2002). For the majority of cases, treatment was conducted within a 15-session intensive format over a 3-week…

Teaching Choice Making to Children with Visual Impairments and Multiple Disabilities in Preschool and Kindergarten Classrooms

ERIC Educational Resources Information Center

Clark, Christine; McDonnell, Andrea P.

2008-01-01

This study examined the effectiveness of an intervention package that included visual accommodations, daily preference assessments, and naturalistic instructional strategies on the accuracy of choice-making responses for three participants with visual impairments and multiple disabilities. It also examined the participants' ability to maintain and…

Daily consumption of orange-fleshed sweet potato with added fat tends to increase total body vitamin A pool size in vitamin A depleted Bangladeshi women

USDA-ARS?s Scientific Manuscript database

We assessed the affect of daily consumption of orange-fleshed sweet potato (OFSP), with or without added fat, on the total body vitamin A (VA) pool size of Bangladeshi women with low initial VA status. Women (n=120) received for 60d either 1) 0 µg RAE/d as boiled white-fleshed sweet potatoes (WFSP) ...

Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes.

PubMed

Marso, Steven P; McGuire, Darren K; Zinman, Bernard; Poulter, Neil R; Emerson, Scott S; Pieber, Thomas R; Pratley, Richard E; Haahr, Poul-Martin; Lange, Martin; Brown-Frandsen, Kirstine; Moses, Alan; Skibsted, Simon; Kvist, Kajsa; Buse, John B

2017-08-24

Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome. Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups. Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529 .).

Experimental metolachlor toxicosis in Nubian goats in the Sudan.

PubMed

Mohamed, O S; Ahmed, K E; Adam, S E; Idris, O F

1994-01-01

Six out of 15 Nubian goats kids were given single oral doses of metolachlor (Dual 720 EC) at 2,000 or 500 mg/kg liveweight and died within 1 h of the dosing. Other 6 goats were given daily oral doses at 200 or 25 mg/kg and died or were slaughtered between days 8 and 25. In goats receiving single doses, the signs of poisoning were convulsive episodes, incoordination of movement, tremors, severe muscular spasms, stiffness, profuse salivation, respiratory distress, abnormal posture and recumbency. In goats receiving metolachlor at daily doses, the signs were similar, but developed slowly. Increases in the activities of serum AST and GGT and in the concentration of urea, and decreases in total protein concentration were correlated with clinical changes and lesions.

[Atomoxetine and piracetam in the treatment of attention deficit hyperactivity disorder in children].

PubMed

Zavadenko, N N; Suvorinova, N Iu

2008-01-01

Therapeutic effect of atomoxetine and piracetam has been assessed in the open controlled study included 42 patients with attention deficit hyperactivity disorder (ADHD), aged from 6 to 13 years. Group 1 (16 patients) received atomoxetine (strattera) in daily dosage 0,8-1,2 mg/kg as a monotherapy for 6 weeks. Patients of group 2 (14 children) received piracetam as a monotherapy in daily dosage 50-70 mg/kg for 6 weeks. No pharmacological therapy was conducted in group 3 (a control one) which included 12 patients with ADHD. The high effectiveness of both atomoxetine and piracetam has been shown. However, comparing to piracetam, the therapeutic effect of atomoxetine was reached earlier (two weeks after the beginning of therapy) and was more pronounced for all components of syndromes.

Effect of optimal daily fertigation on migration of water and salt in soil, root growth and fruit yield of cucumber (Cucumis sativus L.) in solar-greenhouse.

PubMed

Liang, Xinshu; Gao, Yinan; Zhang, Xiaoying; Tian, Yongqiang; Zhang, Zhenxian; Gao, Lihong

2014-01-01

Inappropriate and excessive irrigation and fertilization have led to the predominant decline of crop yields, and water and fertilizer use efficiency in intensive vegetable production systems in China. For many vegetables, fertigation can be applied daily according to the actual water and nutrient requirement of crops. A greenhouse study was therefore conducted to investigate the effect of daily fertigation on migration of water and salt in soil, and root growth and fruit yield of cucumber. The treatments included conventional interval fertigation, optimal interval fertigation and optimal daily fertigation. Generally, although soil under the treatment optimal interval fertigation received much lower fertilizers than soil under conventional interval fertigation, the treatment optimal interval fertigation did not statistically decrease the economic yield and fruit nutrition quality of cucumber when compare to conventional interval fertigation. In addition, the treatment optimal interval fertigation effectively avoided inorganic nitrogen accumulation in soil and significantly (P<0.05) increased the partial factor productivity of applied nitrogen by 88% and 209% in the early-spring and autumn-winter seasons, respectively, when compared to conventional interval fertigation. Although soils under the treatments optimal interval fertigation and optimal daily fertigation received the same amount of fertilizers, the treatment optimal daily fertigation maintained the relatively stable water, electrical conductivity and mineral nitrogen levels in surface soils, promoted fine root (<1.5 mm diameter) growth of cucumber, and eventually increased cucumber economic yield by 6.2% and 8.3% and partial factor productivity of applied nitrogen by 55% and 75% in the early-spring and autumn-winter seasons, respectively, when compared to the treatment optimal interval fertigation. These results suggested that optimal daily fertigation is a beneficial practice for improving crop yield and the water and fertilizers use efficiency in solar greenhouse.

Effect of Optimal Daily Fertigation on Migration of Water and Salt in Soil, Root Growth and Fruit Yield of Cucumber (Cucumis sativus L.) in Solar-Greenhouse

PubMed Central

Liang, Xinshu; Gao, Yinan; Zhang, Xiaoying; Tian, Yongqiang; Zhang, Zhenxian; Gao, Lihong

2014-01-01

Inappropriate and excessive irrigation and fertilization have led to the predominant decline of crop yields, and water and fertilizer use efficiency in intensive vegetable production systems in China. For many vegetables, fertigation can be applied daily according to the actual water and nutrient requirement of crops. A greenhouse study was therefore conducted to investigate the effect of daily fertigation on migration of water and salt in soil, and root growth and fruit yield of cucumber. The treatments included conventional interval fertigation, optimal interval fertigation and optimal daily fertigation. Generally, although soil under the treatment optimal interval fertigation received much lower fertilizers than soil under conventional interval fertigation, the treatment optimal interval fertigation did not statistically decrease the economic yield and fruit nutrition quality of cucumber when compare to conventional interval fertigation. In addition, the treatment optimal interval fertigation effectively avoided inorganic nitrogen accumulation in soil and significantly (P<0.05) increased the partial factor productivity of applied nitrogen by 88% and 209% in the early-spring and autumn-winter seasons, respectively, when compared to conventional interval fertigation. Although soils under the treatments optimal interval fertigation and optimal daily fertigation received the same amount of fertilizers, the treatment optimal daily fertigation maintained the relatively stable water, electrical conductivity and mineral nitrogen levels in surface soils, promoted fine root (<1.5 mm diameter) growth of cucumber, and eventually increased cucumber economic yield by 6.2% and 8.3% and partial factor productivity of applied nitrogen by 55% and 75% in the early-spring and autumn-winter seasons, respectively, when compared to the treatment optimal interval fertigation. These results suggested that optimal daily fertigation is a beneficial practice for improving crop yield and the water and fertilizers use efficiency in solar greenhouse. PMID:24475204

Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study.

PubMed

Dimopoulos, Meletios; Siegel, David S; Lonial, Sagar; Qi, Junyuan; Hajek, Roman; Facon, Thierry; Rosinol, Laura; Williams, Catherine; Blacklock, Hilary; Goldschmidt, Hartmut; Hungria, Vania; Spencer, Andrew; Palumbo, Antonio; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Sun, Linda; Vuocolo, Scott; Anderson, Kenneth C

2013-10-01

We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (≥18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1:1) using an interactive voice response system to receive 21 day cycles of bortezomib (1·3 mg/m(2) intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1-14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage ≥2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or ≥2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number 00773747. Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7·63 months (95% CI 6·87-8·40) in the vorinostat group and 6·83 months (5·67-7·73) in the placebo group (hazard ratio [HR] 0·77, 95% CI 0·64-0·94; p=0·0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most common grade 3-4 adverse events were thrombocytopenia (143 [45%] patients in the vorinostat group vs 77 [24%] patients in the placebo group), neutropenia (89 [28%] vs 80 [25%]), and anaemia (53 [17%] vs 40 [13%]). Although the combination of vorinostat and bortezomib prolonged PFS relative to bortezomib and placebo, the clinical relevance of the difference in PFS between the two groups is not clear. Different treatment schedules of bortezomib and vorinostat might improve tolerability and enhance activity. Merck. Copyright © 2013 Elsevier Ltd. All rights reserved.

Retrieving atmospheric transmissivity for biologically active daily dose, in various european sites

NASA Astrophysics Data System (ADS)

de La Casinière, A.; Touré, M. L.; Lenoble, J.; Cabot, T.

2003-04-01

In the frame of the European Project EDUCE, global UV irradiance spectra recorded all along the year in several European sites are stored in a common database located in Finland. From the spectra set of some of these stations, are calculated atmospheric transmissivities for daily doses of four biologically active UV radiation, namely: UV-B, erythema, DNA damage, and plant damage. A transmissivity is defined as the ratio of the ground level value of the daily dose of interest to its corresponding extra-atmospheric value. Multiple linear correlation of the various transmissivities with three predictors (daily sunshine fraction, cosine of the daily minimum SZA, and daily total ozone column) assumed to be independent variables, are done for year 2000. The coefficients obtained from year 2000 correlation in a given site are expected to retrieve, from the local predictors, the daily dose for year 2001 in the same site, the average error being lesser than 10% for monthly mean values, and lesser than 5% for three-monthly mean values, depending on the daily dose type. Comparison of yearly mean daily doses retrieved in a given site from coefficients obtained in other sites is also presented.

Quantifying Ecological Memory of Plant and Ecosystem Processes in Variable Environments

NASA Astrophysics Data System (ADS)

Ogle, K.; Barron-Gafford, G. A.; Bentley, L.; Cable, J.; Lucas, R.; Huxman, T. E.; Loik, M. E.; Smith, S. D.; Tissue, D.

2010-12-01

Precipitation, soil water, and other factors affect plant and ecosystem processes at multiple time scales. A common assumption is that water availability at a given time directly affects processes at that time. Recent work, especially in pulse-driven, semiarid systems, shows that antecedent water availability, averaged over several days to a couple weeks, can be just as or more important than current water status. Precipitation patterns of previous seasons or past years can also impact plant and ecosystem functioning in many systems. However, we lack an analytical framework for quantifying the importance of and time-scale over which past conditions affect current processes. This study explores the ecological memory of a variety of plant and ecosystem processes. We use memory as a metaphor to describe the time-scale over which antecedent conditions affect the current process. Existing approaches for incorporating antecedent effects arbitrarily select the antecedent integration period (e.g., the past 2 weeks) and the relative importance of past conditions (e.g., assign equal or linearly decreasing weights to past events). In contrast, we utilize a hierarchical Bayesian approach to integrate field data with process-based models, yielding posterior distributions for model parameters, including the duration of the ecological memory (integration period) and the relative importance of past events (weights) to this memory. We apply our approach to data spanning diverse temporal scales and four semiarid sites in the western US: leaf-level stomatal conductance (gs, sub-hourly scale), soil respiration (Rs, hourly to daily scale), and net primary productivity (NPP) and tree-ring widths (annual scale). For gs, antecedent factors (daily rainfall and temperature, hourly vapor pressure deficit) and current soil water explained up to 72% of the variation in gs in the Chihuahuan Desert, with a memory of 10 hours for a grass and 4 days for a shrub. Antecedent factors (past soil water, temperature, photosynthesis rates) explained 73-80% of the variation in sub-daily and daily Rs. Rs beneath shrubs had a moisture and temperature memory of a few weeks, while Rs in open space and beneath grasses had a memory of 6 weeks. For pinyon pine ring widths, the current and previous year accounted for 85% of the precipitation memory; for the current year, precipitation received between February and June was most important. A similar result emerged for NPP in the short grass steppe. In both sites, tree growth and NPP had a memory of 3 years such that precipitation received >3 years ago had little influence. Understanding ecosystem dynamics requires knowledge of the temporal scales over which environmental factors influence ecological processes, and our approach to quantifying ecological memory provides a means to identify underlying mechanisms.

Lycopene

MedlinePlus

... specific lycopene supplement by mouth (LycoRed, Jagsonpal Pharmaceuticals, India) for 2 weeks or receiving a single injection ... taking a specific lycopene supplement (LycoRed, Jagsonpal Pharmaceuticals, India) by mouth daily for 6 months lowers total ...

Insulin pump patient characteristics and glucose control in the hospitalized setting.

PubMed

Kannan, Subramanian; Satra, Ankita; Calogeras, Ellen; Lock, Patricia; Lansang, M Cecilia

2014-05-01

Patients' knowledge of their insulin pumps and glucose control during hospitalization has not been studied. The aim was to study the determinants of glycemic control in patients using continuous subcutaneous insulin infusion (CSII) in the hospital. Three groups of patients were identified: those who did not need any inpatient education and continued on CSII (gorup A), those who received education then continued on CSII (group B), and those for whom CSII was not appropriate and were treated with multiple daily insulin injections (gorup C). We compared the measures of glycemic control between the 3 groups and analyzed which variables impacted glucose control. There were 50 patients, with 51 hospital admissions, 57% males, mean age 48 ± 13 years, 86% had type 1 diabetes (T1DM). The mean DM duration was 26 ± 14 years, mean duration of CSII use was 8.7 ± 6 years, and mean HbA1c was 7.6 ± 1.4%. The mean duration of hospital stay was 5.6 ± 4.6 days. Mean blood glucose (BG) and frequency of hyperglycemia and hypoglycemic events among the 3 groups adjusted for their duration of hospital stay were not statistically different. None of the patients developed diabetic ketoacidosis while using their pump. Stepwise multivariate analysis revealed knowledge of hypoglycemia correction was the single most important predictor of mean BG (P < .001). Patients who received inpatient education performed similarly to patients who did not need inpatient education. Patients who receive inpatient education on CSII fare similar as patients who did not require inpatient education. © 2014 Diabetes Technology Society.

Effects of daily pyrantel tartrate on strongylid population dynamics and performance parameters of young horses repeatedly infected with cyathostomins and Strongylus vulgaris.

PubMed

Reinemeyer, C R; Prado, J C; Andersen, U V; Nielsen, M K; Schricker, B; Kennedy, T

2014-08-29

Strongylid infections are ubiquitous in grazing horse populations. Infections with cyathostomin (small strongyle) and strongylin (large strongyle) nematodes have long been associated with clinical disease in horses, but little is known about their subclinical impact. A masked, randomized, controlled study was conducted to evaluate the effects of daily administration of pyrantel tartrate on body condition scores, weight gain, fecal egg counts, and total worm counts of young horses repeatedly inoculated with strongylid larvae. Twenty eight immature horses were treated with larvicidal anthelmintic regimens and randomly allocated to two groups. Group 1 horses were given a pelleted placebo product once daily, and those in Group 2 received pyrantel tartrate once daily at ∼ 2.64 mg/kg body weight. On five days during each week, ∼ 5000 infective cyathostomin larvae were administered to each horse. In addition, horses received ∼ 25 infective Strongylus vulgaris larvae once weekly. Horses were maintained on pasture for 154 days and had ad libitum access to grass hay throughout. At approximate, 14-day intervals, body weights were measured, body condition scores were assigned, fecal samples were collected for egg counts, and blood samples were collected for measurement of S. vulgaris antibodies and various physiologic parameters. After 22 weeks at pasture and 14-17 days in confinement, horses were euthanatized and necropsied. Nematodes were recovered and counted from aliquots of organ contents, representative samples of large intestinal mucosa, and the root of the cranial mesenteric artery. Daily treatment with pyrantel tartrate at the recommended dosage significantly reduced numbers of adult cyathostomins in the gut lumen and early third-stage larvae in the cecal mucosa, increased the proportions of fourth-stage larvae in the gut contents, and was accompanied by significant improvements in body condition scores. Fecal egg counts of horses receiving daily pyrantel tartrate were significantly reduced, with percentages of efficacy ranging from 84.4% to 98.9%, but egg counts of both groups increased significantly over the course of the study. Treatment also significantly reduced the numbers of S. vulgaris larvae in the cranial mesenteric artery by 99.2%. Serum antibodies to S. vulgaris apparently persisted from pre-enrollment infections, but ELISA values gradually declined over the course of the study. This study has provided useful insights into the effects of daily pyrantel tartrate on the dynamics of cyathostomin infection, and into some subclinical effects of strongylid parasitism in horses. Copyright © 2014 Elsevier B.V. All rights reserved.

Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study.

PubMed

Clotet, Bonaventura; Feinberg, Judith; van Lunzen, Jan; Khuong-Josses, Marie-Aude; Antinori, Andrea; Dumitru, Irina; Pokrovskiy, Vadim; Fehr, Jan; Ortiz, Roberto; Saag, Michael; Harris, Julia; Brennan, Clare; Fujiwara, Tamio; Min, Sherene

2014-06-28

Dolutegravir has been shown to be non-inferior to an integrase inhibitor and superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI). In FLAMINGO, we compared dolutegravir with darunavir plus ritonavir in individuals naive for antiretroviral therapy. In this multicentre, open-label, phase 3b, non-inferiority study, HIV-1-infected antiretroviral therapy-naive adults with HIV-1 RNA concentration of 1000 copies per mL or more and no resistance at screening were randomly assigned (1:1) to receive either dolutegravir 50 mg once daily or darunavir 800 mg plus ritonavir 100 mg once daily, with investigator-selected tenofovir-emtricitabine or abacavir-lamivudine. Randomisation was stratified by screening HIV-1 RNA (≤100,000 or >100,000 copies per mL) and nucleoside reverse transcriptase inhibitor (NRTI) selection. The primary endpoint was the proportion of patients with HIV-1 RNA concentration lower than 50 copies per mL (Food and Drug Administration [FDA] snapshot algorithm) at week 48 with a 12% non-inferiority margin. This trial is registered with ClinicalTrials.gov, NCT01449929. Recruitment began on Oct 31, 2011, and was completed on May 24, 2012, in 64 research centres in nine countries worldwide. Of 595 patients screened, 484 patients were included in the analysis (242 in each group). At week 48, 217 (90%) patients receiving dolutegravir and 200 (83%) patients receiving darunavir plus ritonavir had HIV-1 RNA of less than 50 copies per mL (adjusted difference 7·1%, 95% CI 0·9-13·2), non-inferiority and on pre-specified secondary analysis dolutegravir was superior (p=0·025). Confirmed virological failure occurred in two (<1%) patients in each group; we recorded no treatment-emergent resistance in either group. Discontinuation due to adverse events or stopping criteria was less frequent for dolutegravir (four [2%] patients) than for darunavir plus ritonavir (ten [4%] patients) and contributed to the difference in response rates. The most commonly reported (≥10%) adverse events were diarrhoea (dolutegravir 41 [17%] patients vs darunavir plus ritonavir 70 [29%] patients), nausea (39 [16%] vs 43 [18%]), and headache (37 [15%] vs 24 [10%]). Patients receiving dolutegravir had significantly fewer low-density lipoprotein values of grade 2 or higher (11 [2%] vs 36 [7%]; p=0·0001). Once-daily dolutegravir was superior to once-daily darunavir plus ritonavir. Once-daily dolutegravir in combination with fixed-dose NRTIs represents an effective new treatment option for HIV-1-infected, treatment-naive patients. ViiV Healthcare and Shionogi & Co. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmacokinetics and Safety of Tenofovir in HIV-infected Women during Labor and their Infants During the First Week of Life

PubMed Central

Mirochnick, Mark; Taha, Taha; Kreitchmann, Regis; Nielsen-Saines, Karin; Kumwenda, Newton; Joao, Esau; Pinto, Jorge; Santos, Breno; Parsons, Teresa; Kearney, Brian; Emel, Lynda; Herron, Casey; Richardson, Paul; Hudelson, Sarah E.; Eshleman, Susan H.; George, Kathleen; Fowler, Mary Glenn; Sato, Paul; Mofenson, Lynne

2013-01-01

Background Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking. Methods HPTN 057 was a phase 1, open label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses day 0, 3 and 5; maternal 900 mg doses/infant 6 mg/kg doses day 0, 3 and 5; maternal 600 mg doses/infant 6 mg/kg doses daily ×7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants. Plasma, amniotic fluid and breast milk tenofovir concentrations were determined by liquid chromatographic – tandem mass spectrometric assay. The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL, the median trough tenofovir concentration in adults receiving standard chronic TDF dosing. Results 122 mother-infant pairs from Malawi and Brazil were studied. Tenofovir exposure in mothers receiving 600 mg and 900 mg exceeded that in non-pregnant adults receiving standard 300 mg doses. Tenofovir elimination in the infants was equivalent to that in older children and adults and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74–97% of infants receiving daily dosing. Conclusion A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in studies of TDF efficacy for HIV PMTCT and early infant treatment. PMID:23979002

Diets labelled with (13)C-starch and (15)N-protein reveal daily rhythms of nutrient use in gilthead sea bream (Sparus aurata).

PubMed

Felip, Olga; Blasco, Josefina; Ibarz, Antoni; Martín-Pérez, Miguel; Fernández-Borràs, Jaume

2015-01-01

All functions in animals rely on daily rhythms, and mealtime can act as a rhythm-marker of nutrients assimilation and use. The effects of meal timing and food composition on carbohydrate use and protein retention of gilthead sea bream were studied. Three groups were fed twice a day (10am and at 5pm) for two months with two alternating diets: a commercial diet (Cd) and a high-carbohydrate, low-protein diet (Ed). The Ed/Cd group received the Ed diet in the morning and the Cd diet in the afternoon, and the Cd/Ed group received these diets in the reverse order. The Cd/Cd group only received the commercial diet (control group). After 56days, two force-feeding experiments (PF1 and PF2) measured for all three groups the fate of a single meal labelled with (15)N-protein and (13)C-starch through the retention of both isotopes in the main organs and tissue reserves. In PF1 fish were fed at 10am (morning mealtime), and in PF2 at 5pm (afternoon mealtime). Fish were sampled at the next two mealtimes (PF1: 7 and 24h post-feeding, PF2: 17 and 24h post-feeding). Nutrients recovery differed according to, first, the dietary regime, and second, the last meal received (Cd or Ed). Daily lower protein intake was compensated with higher protein retention combined with more use of carbohydrates for energy. Nevertheless, carbohydrates from the morning meal were used more efficiently. So, the use of carbohydrate for energy production and protein for growth can be improved by adjusting diet composition and mealtime. Copyright © 2014 Elsevier Inc. All rights reserved.

Synergistic effects of aerobic exercise and cognitive training on cognition, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline: study protocol for a randomized controlled trial.

PubMed

Yeh, Ting-Ting; Wu, Ching-Yi; Hsieh, Yu-Wei; Chang, Ku-Chou; Lee, Lin-Chien; Hung, Jen-Wen; Lin, Keh-Chung; Teng, Ching-Hung; Liao, Yi-Han

2017-08-31

Aerobic exercise and cognitive training have been effective in improving cognitive functions; however, whether the combination of these two can further enhance cognition and clinical outcomes in stroke survivors with cognitive decline remains unknown. This study aimed to determine the treatment effects of a sequential combination of aerobic exercise and cognitive training on cognitive function and clinical outcomes. Stroke survivors (n = 75) with cognitive decline will be recruited and randomly assigned to cognitive training, aerobic exercise, and sequential combination of aerobic exercise and cognitive training groups. All participants will receive training for 60 minutes per day, 3 days per week for 12 weeks. The aerobic exercise group will receive stationary bicycle training, the cognitive training group will receive cognitive-based training, and the sequential group will first receive 30 minutes of aerobic exercise, followed by 30 minutes of cognitive training. The outcome measures involve cognitive functions, physiological biomarkers, daily function and quality of life, physical functions, and social participation. Participants will be assessed before and immediately after the interventions, and 6 months after the interventions. Repeated measures of analysis of variance will be used to evaluate the changes in outcome measures at the three assessments. This trial aims to explore the benefits of innovative intervention approaches to improve the cognitive function, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline. The findings will provide evidence to advance post-stroke cognitive rehabilitation. ClinicalTrials.gov, NCT02550990 . Registered on 6 September 2015.

Effects of Arctium lappa on Cadmium-Induced Damage to the Testis and Epididymis of Adult Wistar Rats.

PubMed

Predes, Fabricia de Souza; Diamante, M A S; Foglio, M A; Dolder, H

2016-10-01

The protective role of Arctium lappa (AL) on the testes of rats acutely exposed to cadmium (Cd) was tested. The rats were randomly divided into a control group (C-group) and three major experimental groups, which were further subdivided into minor groups (n = 6) according to the experimental period (7 or 56 days). The C-group was subdivided into C-7 and C-56 [receiving a single saline solution, intraperitoneal (i.p.), on the first day]; the AL-group, AL-7, and AL-56, received AL extract (300 mg/kg/daily); the Cd group, Cd-7 and Cd-56, received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) on the first day; the CdAL group, CdAL-7 and CdAL-56, received the same Cd dose, followed by AL extract. Water or AL extract was administered daily by gavage. After either 7 or 56 days, the testis and accessory glands were removed after whole-body perfusion. Exposure to Cd and CdAL decreased the weight of the testis and epididymis, the gonadosomatic index, seminiferous tubular (ST) diameter, and ST volumetric proportion, and increased the volumetric proportion of interstitium after 56 days. In the epididymis caput, the tubular volumetric proportion decreased along with an increase of interstitial volumetric proportion and epithelium height after 56 days. The alterations observed were less severe only after 7 days. A progressive testicular damage resulted mainly in tubules lined only by Sertoli cells. The sperm number and cell debris decreased in the epididymis. We demonstrated that the testicular damage induced by single acute i.p. exposure to Cd occurred despite the daily oral intake of AL extract.

The costs of fluid overload in the adult intensive care unit: is a small-volume infusion model a proactive solution?

PubMed Central

Child, Debra L; Cao, Zhun; Seiberlich, Laura E; Brown, Harold; Greenberg, Jordan; Swanson, Anne; Sewall, Martha R; Robinson, Scott B

2015-01-01

Purpose Fluid overload (FO) in critically ill patients remains a challenging clinical dilemma, and many continuous intravenous (IV) medications in the US are being delivered as a dilute solution, adding significantly to a patient’s daily intake. This study describes the costs and outcomes of FO in patients receiving multiple continuous infusions. Materials and methods A retrospective study was conducted using a hospital administrative database covering >500 US hospitals. An FO cohort included adult intensive care unit (ICU) patients with a central line receiving IV loop diuretics and 2+ continuous IV infusions on 50%+ of their ICU days; a directly matched non-FO cohort included patients without IV diuretic use. The primary outcome of the study was total hospitalization costs per visit. Additional outcomes were ICU costs, mortality, total and ICU length of stay (LOS), 30-day readmission rates, and ventilator use. Unadjusted descriptive analysis was performed using chi-squared or paired t-tests to compare outcomes between the two cohorts. Results A total of 63,974 patients were identified in each cohort. The total hospitalization cost per visit for the FO cohort was US$15,344 higher than the non-FO cohort (US$42,386 vs US$27,042), and the ICU cost for the FO cohort was US$5,243 higher than the non-FO cohort (US$10,902 vs US$5,659). FO patients had higher mortality (20% vs 16.8%), prolonged LOS (11.5 vs 8.0 days), longer ICU LOS (6.2 vs 3.6 days), higher risk of 30-day readmission (21.8% vs 21.3%), and ventilator usage (47.7% vs 28.3%) than the non-FO cohort (all P<0.05). Conclusion In patients receiving multiple continuous infusions, FO is associated with increased health care resources and costs. Maximally concentrating medications and proactively providing continuous medications in small-volume infusions (SVI) could be a potential solution to prevent iatrogenic FO in critically ill patients. Further prospective research is warranted to assess the impact of the SVI dispensing model on patient outcomes and health care costs. PMID:25548524

Potentially inappropriate medication use in nursing homes: an observational study using the NORGEP-NH criteria.

PubMed

Nyborg, Gunhild; Brekke, Mette; Straand, Jørund; Gjelstad, Svein; Romøren, Maria

2017-09-19

Frail residents in the nursing home sector call for extra care in prescribing. The Norwegian General Practice Nursing Home (NORGEP-NH) list of 34 explicit criteria for potentially inappropriate medication use in nursing homes was developed explicitly for this population. The aim of this study was to employ the NORGEP-NH Criteria to study the extent of potentially inappropriate medication use among nursing home residents and explore possible associated factors. Cross-sectional observational pharmacoepidemiological study from residents in nursing homes in the county of Vestfold, Norway. Data collected 2009-11 included residents' demographic and clinical status and all medications, regular and on demand. 881 patients from 30 institutions (mean 85.9 years, 68.6% female), were included. According to NORGEP-NH, 43.8% were prescribed at least one potentially inappropriate regular medication, and 9.9% regularly received three or more potentially inappropriate medications. When also including a) the NORGEP-NH Deprescribing Criteria and b) including drugs prescribed for use as needed, 92.7% of all residents received medication that needs particular surveillance according to the NORGEP-NH. 69.7% of the nursing home residents used at least one psychotropic drug regularly. Female residents received more often than males at least one potentially inappropriate regular medication (OR 1.60, p=0.007). Regarding the prescription of three or more concomitant psychotropic medications, odds ratio for females was 1.79 (p=0.03) compared to males. Residents with the best performance in activities of daily living, and residents residing in long-term wards, had higher risk of using three or more psychotropic drugs. Use of multiple psychoactive drugs increased the risk of falls in the course of an acute episode of infection or dehydration (odds ratio 1.70, p=0.009). Prevalence of potentially inappropriate medications in nursing homes according to the NORGEP-NH was extensive, and especially the use of multiple psychotropic drugs. The high prevalence found in this study shows that there is a need for higher awareness of medication use and side effects in the elderly population. Retrospectively registered. Data obtained from clinical trial NCT01023763 registered with ClinicalTrials.gov 12/01/2009.

Reconstructing surface wave profiles from reflected acoustic pulses using multiple receivers.

PubMed

Walstead, Sean P; Deane, Grant B

2014-08-01

Surface wave shapes are determined by analyzing underwater reflected acoustic signals collected at multiple receivers. The transmitted signals are of nominal frequency 300 kHz and are reflected off surface gravity waves that are paddle-generated in a wave tank. An inverse processing algorithm reconstructs 50 surface wave shapes over a length span of 2.10 m. The inverse scheme uses a broadband forward scattering model based on Kirchhoff's diffraction formula to determine wave shapes. The surface reconstruction algorithm is self-starting in that source and receiver geometry and initial estimates of wave shape are determined from the same acoustic signals used in the inverse processing. A high speed camera provides ground-truth measurements of the surface wave field for comparison with the acoustically derived surface waves. Within Fresnel zone regions the statistical confidence of the inversely optimized surface profile exceeds that of the camera profile. Reconstructed surfaces are accurate to a resolution of about a quarter-wavelength of the acoustic pulse only within Fresnel zones associated with each source and receiver pair. Multiple isolated Fresnel zones from multiple receivers extend the spatial extent of accurate surface reconstruction while overlapping Fresnel zones increase confidence in the optimized profiles there.

Step wise, multiple objective calibration of a hydrologic model for a snowmelt dominated basin

USGS Publications Warehouse

Hay, L.E.; Leavesley, G.H.; Clark, M.P.; Markstrom, S.L.; Viger, R.J.; Umemoto, M.

2006-01-01

The ability to apply a hydrologic model to large numbers of basins for forecasting purposes requires a quick and effective calibration strategy. This paper presents a step wise, multiple objective, automated procedure for hydrologic model calibration. This procedure includes the sequential calibration of a model's simulation of solar radiation (SR), potential evapotranspiration (PET), water balance, and daily runoff. The procedure uses the Shuffled Complex Evolution global search algorithm to calibrate the U.S. Geological Survey's Precipitation Runoff Modeling System in the Yampa River basin of Colorado. This process assures that intermediate states of the model (SR and PET on a monthly mean basis), as well as the water balance and components of the daily hydrograph are simulated, consistently with measured values.